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iPS cell technologies: significance and applications to …

In 2006, we demonstrated that mature somatic cells can be reprogrammed to a pluripotent state by gene transfer, generating induced pluripotent stem (iPS) cells. Since that time, there has been an enormous increase in interest regarding the application of iPS cell technologies to medical science, in particular for regenerative medicine and human disease modeling. In this review article, we outline the current status of applications of iPS technology to cell therapies (particularly for spinal cord injury), as well as neurological disease-specific iPS cell research (particularly for Parkinsons disease and Alzheimers disease). Finally, future directions of iPS cell research are discussed including a) development of an accurate assay system for disease-associated phenotypes, b) demonstration of causative relationships between genotypes and phenotypes by genome editing, c) application to sporadic and common diseases, and d) application to preemptive medicine.

The 2012 Nobel Prize in Physiology or Medicine was awarded for The discovery that mature cells can be reprogrammed to become pluripotent. First, we would like to consider the significance of this research. The lives of mammals, including humans, begin with the fertilization of an egg by a sperm cell. In humans, a blastocyst composed of 70-100 cells forms by approximately 5.5 days after fertilization. The blastocyst is composed of the inner cell mass, the cell population that has the ability to differentiate into the various cells that constitute the body (pluripotency), and the trophoblast, the cells that develop into the placenta and extra-embryonic tissues and do not contribute cells to the body. In the embryonic stage, the pluripotent cells of the inner cell mass differentiate into the three germ layers, endoderm, mesoderm, and ectoderm, which will form specific organs and tissues containing somatic stem cells with limited differentiation potencies. These somatic stem cells continue to divide and differentiate, and, by adulthood, an individual composed of 60 trillion cells is produced. Somatic stem cells born in the fetal period actively divide, and are involved in the formation and growth of various organs. However, even in the adult, somatic stem cells persist in niches in every organ and tissue, and play an important role in maintaining organ and tissue homeostasis. When cells in the inner cell mass are removed at the blastocyst stage and cultured in vitro, pluripotent embryonic stem (ES) cells are obtained. Thus, in the normal process of development, cell differentiation of the three germ layers proceeds from the simple stages of the fertilized egg and blastocyst, and ultimately produces an individual consisting of a complex cellular society.

In 1893, August Weismann argued that only germ cells (eggs and spermatozoa) maintain a determinant, which was described as heritable information essential to decide on the functions and features of all somatic cells in the body [1]. In his germ plasm theory, the determinants are lost or irreversibly inactivated in differentiated somatic cells.

It took more than 50 years for researchers to rewrite this dogma. In 1962, Sir John Gurdon demonstrated the acquisition of pluripotency by reprogramming cells to their initial stage using a novel research technique, i.e., producing cloned individuals by transferring somatic cell nuclei into eggs [2]. However, for many years, that result was regarded as a special case limited to frogs alone. The production of Dolly the sheep by transferring the nucleus of a somatic cell (mammary gland epithelial cell) by Sir Ian Wilmut in the late 1990s [3] showed that cloning could also be applied to mammals.

These brilliant previous works led to our studies that culminated in the induction of pluripotency in mouse somatic cells in 2006, using retroviral vectors to introduce four genes that encode transcription factors i.e., Oct4, Sox2, Klf4, and c-Myc. We designated these cells as iPS cells [4]. In 2007, we succeeded in generating human iPS cells using genes encoding the same four transcription factors [1]. The results of this research showed that although the developmental process was thought to be irreversible, by introducing key genes into differentiated adult cells the cells could be reset to a state in the extremely early stage of development in which they possessed pluripotency. That is, the results demonstrated that the differentiation process was reversible. This startling discovery made it necessary to rewrite the embryology textbooks.

Three major lines of research led us to the production of iPS cells [

] (Figure

). The first, as described above, was nuclear reprogramming initiated by Sir John Gurdon in his research of cloning frogs by nuclear transfer in 1962 [

] and by Sir Ian Wilmut, who cloned a mammal for the first time in 1997 [

]. In addition, Takashi Tada showed that mouse ES cells contain factors that induce reprogramming in 2001 [

]. The second line of research was factor-mediated cell fate conversion, initiated by Harold Weintraub, who showed that fibroblasts can be converted into the muscle lineage by transduction with the

gene, which encodes a muscle lineage-specific basic helix-loop-helix transcription factor in 1987 [

]. The third line of research was the development of mouse ES cells, initiated by Sir Martin Evans and Gail Martin in 1981 [

,

]. Austin Smith established culture conditions for mouse ES cells and identified many factors essential for pluripotency including leukemia inhibitory factor (LIF) in 1988 [

]. Later, he developed the method to induce the ground state of mouse ES cell self-renewal using inhibitors for mitogen-activated protein kinase and glycogen synthase kinase 3 [

], which supports the establishment of fully reprogrammed mouse iPS cells. Furthermore, James Thomson generated human ES cells [

] and established their optimal culture conditions using fibroblast growth factor-2 (FGF-2). Without these previous studies, we could never have generated iPS cells. Interest rapidly escalated, and, in tandem with the birth of iPS cell technology, pluripotency leapt into the mainstream of life sciences research in the form of reprogramming technology [

]. However, there remain many unanswered questions regarding reprogramming technology. What are the reprogramming factors in the egg cytoplasm that are active in cloning technology? What do they have in common with the factors required to establish iPS cells and what are the differences? What kind of epigenetic changes occur in association with the reprogramming?

The history of investigations of cellular reprogramming that led to the development of iPS cells. Our generation of iPS cells in 2006 [4] became possible due to three scientific lines of investigation: 1) nuclear reprogramming, 2) factor-mediated cell fate conversion, and 3) ES cells. See the text for details (modified from Reference [5] with permission).

Apart from basic research in embryology, broad interest has been drawn to the following possible applications of iPS cell research: (1) regenerative medicine, including elucidating disease pathologies and drug discovery research using iPS cell disease models, and (2) medical treatments (Figure

). In this review, we describe these potential applications in the context of the results of our own research.

The application of iPS cell technologies to medical science. iPS cell technologies can be used for medical science including 1) cell therapies and 2) disease modeling or drug development. See the text for details.

iPS cells can be prepared from patients themselves and therefore great expectations have been placed on iPS cell technology because regenerative medicine can be implemented in the form of autografts presumably without any graft rejection reactions. Although there have been some controversies [

], the immunogenicity of terminally differentiated cells derived from iPS cells can be negligible [

]. Moreover, there has been substantial interest in the possibility of regenerative medicine without using the patients own cells; that is, using iPS cell stocks that have been established from donor somatic cells that are homozygous at the three major human leukocyte antigen (HLA) gene loci and match the patients HLA type [

]. The development of regenerative medicine using iPS cells is being pursued in Japan and the USA for the treatment of patients with retinal diseases, including age-related macular degeneration [

], spinal cord injuries [

], Parkinsons disease (PD) [

,

], corneal diseases [

], myocardial infarction [

,

], diseases that cause thrombocytopenia, including aplastic anemia and leukemia [

,

], as well as diseases such as multiple sclerosis (MS) and recessive dystrophic epidermolysis bullosa [

] (Table

).

Planned clinical trials of iPS cell-based therapies

Masayo Takahashi, (RIKEN)

Retinal Pigment Epithelium (sheet)

Age-related macular degeneration (wet type)

Alfred Lane, Anthony Oro, Marius Wernig (Stanford University)

Keratinocytes

Recessive dystrophic epidermolysis bullosa (RDEB)

Mahendra Rao (NIH)

DA neurons

Parkinsons disease

Koji Eto (Kyoto University)

Megakaryocyte

Thrombocytopenia

Jun Takahashi (Kyoto University)

DA neurons

Parkinsons disease

Steve Goldman, (University of Rochester)

Oligodendrocyte precursor cell

Multiple Sclerosis

Hideyuki Okano, Masaya Nakamura (Keio University)

Neural stem/progenitor cells

Spinal Cord Injury

Shigeto Shimmura (Keio University)

Corneal endothelial cells

Corneal endothelial dysfunction

Koji Nishida (Osaka University)

Corneal epithelial cells (sheet)

Corneal epithelial dysfunction and trauma (e.g. StevensJohnson syndrome)

Yoshiki Sawa (Osaka University)

Cardiomyocytes (sheet)

Heart Failure

Keiichi Fukuda (Keio University)

Cardiomyocytes (sphere)

Heart Failure

Yoshiki Sasai and Masayo Takahashi (RIKEN)

Neuroretinal sheet including photoreceptor cells

Retinitis pigmentosa

Advanced Cell Technology

Megakaryocytes

Refractory thrombocytopenia

In 1998, Hideyuki Okano, in collaboration with Steven Goldman, demonstrated for the first time the presence of neural stem/progenitor cells (NS/PCs) in the adult human brain using a neural stem cell marker, the ribonucleic acid (RNA)-binding protein Musashi1 [30, 31]. Research on nerve regeneration then commenced in earnest. That same year, we began regenerative medicine research on neural stem cell transplantation in a rat model of SCI, and have since made progress in developing NS/PC transplantation therapies in experiments on animal models of SCI. First, motor function was restored by transplanting rat fetal central nervous system (CNS)-derived NS/PCs into a rat SCI model [32]. The same study also showed that the sub-acute phase is the optimal time for NS/PC transplantation after SCI. In this study, at least part of the putative mechanism by which NS/PC transplantation restored function was identified in animal models of SCI. Both the cell autonomous effect (such as synaptogenesis between graft-derived neurons and host-derived neurons) and non-cell autonomous (trophic) effects mediated cytokines released from the graft-derived cells are likely contributing to tissue repair and functional recovery. Subsequently, a non-human primate SCI model was developed using the common marmoset, and motor function in that model was restored by transplanting human fetal CNS-derived stem cells [33]. In the same study, a behavioral assay for motor function associated with SCI was developed. Based on these studies, a preclinical research system for cell transplantation therapy was established in a non-human primate SCI model.

Given these findings, we began preparations for clinical studies of human fetal CNS-derived NS/PC transplantation to treat SCI patients. However, with the guidelines for clinical research on human stem cells of the Japanese Ministry of Health, Labor and Welfare that came into effect in 2006, human fetus-derived cells and ES cells became ineligible for use in regenerative medicine. Thus, we had no choice but to change our strategy (human ES cells became eligible for use in the 2013 guidelines). In 2006, one of our research groups (Yamanakas group) established iPS cells from adult mouse skin cells. Hypothesizing that it might be possible to induce NS/PCs from iPS cells, we (Okanos group) turned our attention to iPS cells as a means of obtaining NS/PCs without using fetal or ES cells. Based on conditions that were developed for experiments on mouse ES cells [34, 35], NS/PCs were induced from mouse iPS cells [36]. The following year, we succeeded in restoring motor function by transplanting these mouse iPS cell-derived NS/PCs into a mouse model of SCI, and reported that when good iPS cells -derived NS/PCs, which had been pre-evaluated as non-tumorigenic by the transplantation into the brains of immunocompromised mice, were used for transplantation, motor function was restored for a long period of time without tumors developing [37]. In 2011, we succeeded in restoring motor function by transplanting human iPS cell-derived stem cells into a mouse SCI model [38]. Moreover, in 2012, motor function was restored by transplanting human iPS (line 201B7) cell-derived NS/PCs into the marmoset SCI model, and long-term motor function was recovered without observable tumor formation [39]. This finding was of great significance in terms of preclinical research, and provided a proof of concept that could potentially lead to a treatment method.

Collectively, when mouse or human iPS cells were induced to form NS/PCs and were transplanted into mouse or non-human primate SCI models, long-term restoration of motor function was induced, without tumorigenicity, by selecting a suitable iPS cell line [17, 40]. Considering the sub-acute phase (2-4 weeks after the injury) as the optimal time for iPS cells-derived NS/PCs transplantation for SCI patients, there are following major difficulties with autograft-based cell therapy. First, it takes about a few months to establish iPS cells. Second, it also takes three months to induce them into NS/PCs in vitro. Third, one more year would be required for the quality control including their tumorigenesis.

Considering these, our collaborative team (Okano and Yamanaka laboratories) are currently planning iPS-based cell therapy for SCI patients in the sub-acute phase using clinical-grade integration-free human iPS cell lines that will be generated by Kyoto Universitys Center for iPS Cell Research and Application (CiRA). We will establish a production method, as well as a storage and management system, for human iPS cell-derived NS/PCs for use in clinical research for spinal cord regeneration, build an iPS cell-derived NS/PC stock for regenerative medicine, establish safety screenings against post-transplantation neoplastic transformation, and commence clinical research (Phase IIIa) trials for the treatment of sub-acute phase SCI (Figure

). As these studies progress, the application of iPS cells to treat chronic phase SCI and stroke will be investigated. Significant therapeutic efficacy in the treatment of chronic phase SCI has not been achieved by cell transplantation alone [

]. However, clinical studies are planned using antagonists of axon growth inhibitors, such as Semaphorin3A inhibitors [

], followed by multidisciplinary rehabilitation combination therapies. We aim to perform a clinical trial based on the Pharmaceutical Affairs Act in collaboration with drug companies and to use iPS cell-derived NS/PC stocks for regenerative medicine to establish treatment methods for stroke, MS, and Huntingtons disease.

Strategies for the development of iPS cell-based cell therapy for SCI patients. Our collaborative team (Okanos group at Keio University and Yamanakas group at Kyoto University) have been developing an iPS cell-based cell therapy for SCI since 2006. Our previous preclinical studies have shown that long-term functional restoration can be obtained by transplantation of NS/PCs derived from appropriate iPS cells clones without observable tumor formation [10]. Currently, we aim to develop iPS cells-based cell therapy for SCI patients at sub-acute phase using the clinical grade iPS cell-derived NS/PCs (i.e., the role of Okanos group described in the blue box) which have been prepared from human iPS cell stock (i.e., the role of Yamanakas group described in the yellow box).

Lesion sites are difficult to access in patients with degenerative diseases of the nervous system. Therefore, in past studies, cell biological or biochemical analyses of their pathology centered on forced expression of the causative genes in non-nervous system cultured cell lines and on mice in which the causative gene was knocked out. However, in a few instances, the animal or cell models did not necessarily reflect the human pathology. Identifying cell biological or biochemical changes in the initial stages of the disease, before onset of symptoms, has been difficult given analyses conducted on postmortem brains. However, with the development of iPS cell technologies, it became possible to establish pluripotent stem cells from the somatic cells of anyone, irrespective of race, genetic background, or whether the person exhibits disease symptoms. Thus, it is no exaggeration to say that generation of disease-specific iPS cells using iPS cell technologies is the sole means of reproducing ex vivo phenomena that occur in patients in vivo, particularly for nervous system disorders. The result has been a tremendous desire by investigators who are conducting research on neurological diseases to become engaged in disease-specific iPS cell research [4345].

A variety of disease-specific iPS cells have been used to study nervous system diseases, including amyotrophic lateral sclerosis (ALS) [

], spinal muscular atrophy [

], spinobulbar muscular atrophy [

], Friedreichs ataxia [

], Alzheimers disease (AD) [

], PD [

], Huntingtons disease [

,

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Best Master’s Degrees in Biotechnology 2016

Biotechnology is a top-notch field of study that emerged into the scientific world as a result of revolutions in Biology, Chemistry, Informatics, and Engineering. It is considered to be an applied branch of Biology. Biotechnology helps out this old and respectable field of science keep up with the pace of time and remain competitive in the contemporary world.

With a Master in Biotechnology, students will study the use of living organisms and bioprocesses in technology, engineering, medicine, agriculture and results in all kinds of bioproducts, from genetically modified food to serious cutting-edge devices used to carry out gene therapy. Students in Master in Biotechnology programs may also explore bioinformatics, which is the application of statistics and computer science to the field of molecular biology. Bioinformatics is extremely important for contemporary biological and molecular researches because the data amount there grows by geometric progression and it is necessary to have adequate technology to process it. Bioinformatic methods are widely used for mapping and analyzing DNA and protein samples, as well as for the study of genetics and molecular modeling. Biotechnology and Bioinformatics do a great favour to traditional fields of study, refreshing them with new methods of research, which allows their drastic development, and you can make your contribution with a Master in Biotechnology degree.

Find out about various Master in Biotechnology programs by following the links below. Don't hesitate to send the "Request free information" form to come in contact with the relevant person at the school and get even more information about the specific Master in Biotechnology program you are interested in.

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Current Opinion in Biotechnology – Journal – Elsevier

The Current Opinion journals were developed out of the recognition that it is increasingly difficult for specialists to keep up to date with the expanding volume of information published in their subject. In Current Opinion in Biotechnology, we help the reader by providing in a systematic manner: 1. The views of experts on current advances in biotechnology in a clear and readable form. 2. Evaluations of the most interesting papers, annotated by experts, from the great wealth of original publications.

Division of the subject into sections The subject of biotechnology is divided into themed sections, each of which is reviewed once a year. The amount of space devoted to each section is related to its importance.

Analytical biotechnology Plant biotechnology Food biotechnology Energy biotechnology Environmental biotechnology Systems biology Nanobiotechnology Tissue, cell and pathway engineering Chemical biotechnology Pharmaceutical biotechnology

Selection of topics to be reviewed Section Editors, who are major authorities in the field, are appointed by the Editors of the journal. They divide their section into a number of topics, ensuring that the field is comprehensively covered and that all issues of current importance are emphasised. Section Editors commission reviews from authorities on each topic that they have selected.

Reviews Authors write short review articles in which they present recent developments in their subject, emphasising the aspects that, in their opinion, are most important. In addition, they provide short annotations to the papers that they consider to be most interesting from all those published in their topic over the previous year.

Editorial Overview Section Editors write a short overview at the beginning of the section to introduce the reviews and to draw the reader's attention to any particularly interesting developments. This successful format has made Current Opinion in Biotechnology one of the most highly regarded and highly cited review journals in the field (Impact factor = 8.035).

Ethics in Publishing: General Statement

The Editor(s) and Publisher of this Journal believe that there are fundamental principles underlying scholarly or professional publishing. While this may not amount to a formal 'code of conduct', these fundamental principles with respect to the authors' paper are that the paper should: i) be the authors' own original work, which has not been previously published elsewhere, ii) reflect the authors' own research and analysis and do so in a truthful and complete manner, iii) properly credit the meaningful contributions of co-authors and co-researchers, iv) not be submitted to more than one journal for consideration, and v) be appropriately placed in the context of prior and existing research. Of equal importance are ethical guidelines dealing with research methods and research funding, including issues dealing with informed consent, research subject privacy rights, conflicts of interest, and sources of funding. While it may not be possible to draft a 'code' that applies adequately to all instances and circumstances, we believe it useful to outline our expectations of authors and procedures that the Journal will employ in the event of questions concerning author conduct. With respect to conflicts of interest, the Publisher now requires authors to declare any conflicts of interest that relate to papers accepted for publication in this Journal. A conflict of interest may exist when an author or the author's institution has a financial or other relationship with other people or organizations that may inappropriately influence the author's work. A conflict can be actual or potential and full disclosure to the Journal is the safest course. All submissions to the Journal must include disclosure of all relationships that could be viewed as presenting a potential conflict of interest. The Journal may use such information as a basis for editorial decisions and may publish such disclosures if they are believed to be important to readers in judging the manuscript. A decision may be made by the Journal not to publish on the basis of the declared conflict.

For more information, please refer to: http://www.elsevier.com/wps/find/authorshome.authors/conflictsofinterest

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Biotechnology for Biofuels | Home page

Prof James du Preez is professor of microbiology and former chairperson (2002 2014) of the Department of Microbial, Biochemical & Food Biotechnology at the University of the Free State in Bloemfontein, South Africa. He obtained his PhD in microbiology from the above university in 1980 after completing a major part of his doctoral research at the Swiss Federal Institute of Technology, Zrich, which laid the foundation for his further work in the field of fermentation biotechnology. His special interests include continuous (chemostat) cultures, yeast physiology, the production of heterologous proteins and microbial metabolites, as well as bioethanol production from starchy and lignocellulosic feedstocks, including pentose fermentation by yeasts. The physiology of the yeast Saccharomyces cerevisiae is an ongoing interest.

James has authored close to 100 peer-reviewed articles as well as several other papers and book chapters. Involvement with the science community includes membership of the council of the South African Society for Microbiology and the International Commission for Yeasts. He was the American Society for Microbiologys ambassador to South Africa until 2014. He serves on the editorial board of FEMS Yeast Research and was a guest editor for a thematic issue of FEMS Yeast Research on yeast fermentations and other yeast bioprocesses. He was an associate editor for World Journal of Microbiology and Biotechnology until early 2015, currently is a joint editor-in-chief for Biotechnology for Biofuels and recently served on the Editors Advisory Group of BioMed Central. In 2014 he was appointed external expert on the Biological Production Systems panel of the Swedish Foundation for Strategic Research and in 2015 served for a second term on a grant evaluation panel of the European Research Council. Among honours received are election as member of the Academy of Science of South Africa, the award of a silver medal for exceptional achievement from the South African Society for Microbiology and awards from his home university for research excellence.

Dr Michael Himmel has 30 years of progressive experience in conducting, supervising, and planning research in protein biochemistry, recombinant technology, enzyme engineering, new microorganism discovery, and the physicochemistry of macromolecules. He has also supervised research that targets the application of site-directed-mutagenesis and rational protein design to the stabilization and improvement of important industrial enzymes, especially glycosyl hydrolases.

Dr Himmel has functioned as PI for the DOE EERE Office of the Biomass Program (OBP) since 1992, wherein his responsibilities have included managing research designed to improve cellulase performance, reduce biomass pretreatment costs, and improve yields of fermentable sugars. He has also developed new facilities at NREL for biomass conversion research, including a Cellulase Biochemistry Laboratory, a Biomass Surface Characterization Laboratory, a Protein Crystallography Laboratory, and a new Computational Science Team. Dr. Himmel also serves as the Principal Group Manger of the Biomolecular Sciences Group, where he has supervisory responsibly for 50 staff scientists.

Prof Debra Mohnen received her B.A. in biology from Lawrence University (Wisconsin) and her MS in botany and PhD in plant biology from the University of Illinois. Her PhD research was conducted at the Friedrich Miescher Institute in Basel, Switzerland. She held postdoctoral research associate positions at the USDA's Richard Russell Research Center and at the Complex Carbohydrate Research Center (CCRC) in Athens, GA where she won an NIH National Research Service Award for her postdoctoral research. She was appointed to the CCRC faculty in September 1990 and is currently Professor in the Department of Biochemistry and Molecular Biology and also adjunct faculty member in the Department of Plant Biology and member of the Plant Center at UGA. Dr Mohnen has served on the Committee on the Status of Women in Plant Physiology of the American Society of Plant Physiologists, invited faculty sponsor for the UGA Association for Women in Science (AWIS), past member-at-large in the Cellulose and Renewable Materials Division of the American Chemical Society, and is currently a member of the Council for Chemical and Biochemical Sciences, Chemical Sciences, Geosciences, and Biosciences Division in the Office of Basic Energy Sciences, Office of Science, U.S. Department of Energy. As Co-PI on the NSF-funded Plant Cell Wall Biosynthesis Research Network Dr Mohnen established the originally NSF-funded service CarboSource Services, that provides rare substrates for plant wall polysaccharide synthesis to the research community. Her research centers on the biosynthesis, function and structure of plant cell wall polysaccharides is supported by funding from the USDA, NSF and DOE. Her emphasis is on pectin biosynthesis and pectin function in plants and human health, and on the improvement of plant cell wall structure so as to improve the efficiency of conversion of plant wall biomass to biofuels.

Prof Charles Wyman has devoted most of his career to leading advancement of technology for biological conversion of cellulosic biomass to ethanol and other products. In the fall of 2005, he joined the University of California at Riverside as a Professor of Chemical and Environmental Engineering and the Ford Motor Company Chair in Environmental Engineering with a research focus on pretreatment, enzymatic hydrolysis, and dehydration of cellulosic biomass to produce reactive intermediates for conversion to fuels and chemicals. Before joining UCR, he was the Paul E. and Joan H. Queneau Distinguished Professor in Environmental Engineering Design at the Thayer School of Engineering at Dartmouth College. Dr. Wyman recently founded Vertimass LLC that is devoted to commercialization of novel catalytic technology for simple one-step conversion of ethanol to fungible gasoline, diesel, and jet fuel blend stocks. Dr. Wyman is also cofounder and former Chief Development Officer and Chair of the Scientific Advisory Board for Mascoma Corporation, a startup focused on biomass conversion to ethanol and other products.

Before joining Dartmouth College in the fall of 1998, Dr. Wyman was Director of Technology for BC International and led process development for the first cellulosic ethanol plant planned for Jennings, Louisiana. Between 1978 and 1997, he served as Director of the Biotechnology Center for Fuels and Chemicals at the National Renewable Energy Laboratory (NREL) in Golden, Colorado; Director of the NREL Alternative Fuels Division; and Manager of the Biotechnology Research Branch. During that time, he held several other leadership positions at NREL, mostly focused on R&D for biological conversion of cellulosic biomass to fuels and chemicals. He has also been Manager of Process Development for Badger Engineers, an Assistant Professor of Chemical Engineering at the University of New Hampshire, and a Senior Chemical Engineer with Monsanto Company.

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What are stem cells and bone marrow? – Information and …

There are two different types of stem cell transplants:

To understand these treatments, it first helps to learn how the bone marrow and stem cells work.

Stem cells are blood cells at their earliest stage of development. All blood cells develop from stem cells. The full name for stem cells in the blood and bone marrow is haematopoietic stem cells, but in this booklet we call them stem cells.

Bone marrow is a spongy material inside the bones particularly the bones of the pelvis. The bone marrow is where stem cells are made.

Most of the time, almost all of your stem cells are in the bone marrow. There are usually only a very small number in the blood. Stem cells stay in the bone marrow while they develop into blood cells. Then, once they are fully mature, the blood cells are released into the bloodstream.

The three main types of blood cells are:

Illustration of bone marrow

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The levels of blood cells in your blood are measured in a blood test called a full blood count (FBC). Its often just called a blood count.

The figures below are a guide to the levels usually found in a healthy person.

These figures can vary from hospital to hospital. Your doctor or nurse can tell you what levels they use. They can also vary slightly between people from different ethnic groups.

The figures might look complicated when theyre written down, but in practice theyre used in a straightforward way. For example, youll hear doctors or nurses saying things like your haemoglobin is 140 or your neutrophils are 4.

Most people with cancer or leukaemia soon get used to these figures and what they mean. But you can always ask your medical team to explain if youre not sure.

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Stem Cells and Skin Part 3: It’s the Cytokines …

As human stem cells and their role in skin physiology, wound repair, aging, and rejuvenation is the subject of our own work, we have a lot to say on the subject. As our goal here is education at a consumer level, we struggle mightily to express complex concepts and research results in terms that can be appreciated by all, including non-scientists. But sometimes fine shades of meaning have big consequences, and we dont want to compromise on the bare faced truth mission either. It is frankly a challenge, and Im sure we fail for the most part. So we apologize in advance and ask you to bear with us. Hopefully we will get better at this as time goes on.

In a prior post we introduced the subject of mesenchymal stem cells. Next we will take you a bit further down the path of understanding what these particular stem cells have to do with skin and aging. I thought I would put this in outline form. See if this makes it any easier to digest. Here goes.

Not all stem cells are the same. There are many varieties.

Mesenchymal stem cells (MSCs) are one type; they form a key part of the human bodys defense against injury and stress.

MSCs can be found in many places in the body bone marrow, fat, tooth roots, around blood vessels, etc. Each of these are called niches and reflect the home environment of that type of MSC. There is increasing evidence that marked differences exist in the biology of MSCs that are dependent on the tissue of origin. Indeed this niche factor appears to be the main source of variation in the biological properties of MSCs (De Bari et al., 2008; Augello, Kurth & De Bari, 2010).

Thus, not all MSCs are the same.

MSCs migrate to damaged areas of the body. There they act as first responders. Their primary role is command and control telling local tissue what to do, and organizing cells of the immune system which are the worker bees.

All communication among MSCs and between MSCs and other cells (e.g. damaged skin cells) uses biochemicals called cytokines.

There are hundreds of cytokines, each with a specific message (e.g. hey fibroblasts, lets make some more collagen). Multiple messages are in play at any time in an MSC mediated response. The messages are tightly coordinated so they reach the right cells at the right time for the proper work to be done. Some are very short distance and some are medium or long distance.

Cytokines can be classified into families. Some are growth factors (make more cells), some are chemokines (bring me some phagocytic cells), and many are involved in protein synthesis inside cells they target.

MSC cells themselves can differentiate into needed cells for rebuilding damaged tissue. But it turn out that that is a minor part of what they do, not the major thing. In skin in particular, MSCs as bricks in rebuilding is unlikely except in severe damage (e.g. burns).

Aging skin reflects both intrinsic cell and tissue level changes (senescence) and a process of continual damage (e.g. from sun, chemicals, disease) and repair (via several mechanisms, including calling 911 to bring MSCs to the area).

There are unique MSC-like cells that live in very small numbers in the bottom of hair follicles. This is their niche (remember, not all MSCs are the same). There are also perivascular (around blood vessel) MSCs in the dermis of skin (deeper).

These local stem cells have particular roles to play in maintenance of growth, and replacing senescent cells (all cells die of old age eventually). But in terms of damage, other MSCs migrate to the area from guess where? The bone marrow. Seems like that is the special role of that particular MSC niche.

That scenario will be no surprise to those who know that the bone marrow is also where all the blood cells (red corpuscles and white immune system cells) are made and exported via the blood stream to perform functions throughout the body. In fact, bone marrow MSCs and bone marrow hematopoetic stem cells live in very close proximity in the bone marrow. These are the same cells that get replaced when a bone marrow transplant is performed.

When skin undergoes repair, all these mechanisms must act together in a coordinated fashion. Again, that control seems to be the specialty of marrow-derived MSCs secreting very specific patterns of cytokines. Those cytokine patterns are what determines that the right thing happens at the right time. E.g. you dont want to build new cells until you have mopped up the debris from damaged tissue. That would be like painting over old peeling wallpaper. Ask your local contractor. Demolition happens first, then rebuilding.

When you hear about products that contain stem cells, you should ask several questions. First, you should read Dr. Georges post about plant stem cells (dont work), creams that have nothing to do with stem cells whatsoever except using it as a deceitful marketing term (e.g. Biologics Stem Cell Cream). You can filter these out right away.

That leaves you with human stem cells. Now, you will not find cosmeceutical products on the market that contain human stem cells. That would be considered a biologic by FDA standards, and would be regulated like a drug or device. The reason is that whole cells contain (other peoples) DNA, and may also carry disease.

While human stem cells themselves wont be in any products, they can be grown in culture (in vitro, or outside the body) in a laboratory. When they do so, if they are well fed and happy, they tend to divide to make new daughter cells. When they are doing so, they communicate with one another via cytokines. Remember the messenger molecules we spoke of above? This is the basic language of stem cells. Again, if the conditions are right, they chatter away as they expand in culture (more of them, coming closer together). As they start to crowd up against each other (we call that confluence) the message changes. More of those short distance cytokines are produced. Some are transferred from one cell to next one touching it (we call that a paracrine message). The MSCs start to slow down their proliferation when the numbers reach confluence. At this point the cell biologist may transfer some of those cells to new flasks, where they will be less crowded, and will resume proliferation. This is a called a passage.

Now, if you remove some of the nutrient rich fluid that bathes the MSCs in culture, you will find that it contains a lot of cytokines. This is called conditioned medium. It is cell growth medium conditioned by the many cytokines secreted by the MSCs. Its like capturing a whole bunch of cell-to-cell conversations all at once. An analogy might be your cellular telephony system. If you could grab 5 second sample of all the conversations going through one cell tower, it would indeed be a tower of babble But your cell system is clever enough to sort all those words into the right pathway to make a conversation.

So, here is the discovery that led to a whole new generation of anti-aging skin care products. If you take that conditioned media and put it on skin, you can observe immediate improvements in skin texture, tone and color. If you keep applying it, you will see structural changes (increase collagen production) with diminution of wrinkles. It has interesting side effects. Minor cuts and abrasions heal very quickly. Angry red areas seem to disappear.

That defines the first generation products whose key active ingredients are made by stem cells in vitro. But that is only the start. We now are gaining insight into the stem cytokines themselves, and the patterns they form. We know that they talk about a lot more than growth, and if can discern what they are saying and how they say it (in other words decipher their language) we can change the cytokine composition of the conditioned medium. We can them communicate back with the MSCs in culture in their language. In doing so (I will leave out a lot of proprietary steps here) we can get them to change their message by responding to ours. We can optimize it for different situations. So, it is no longer one product (a bunch of cytokines) but a very clever set of stem cells making products for whatever condition we require.

This is a lot for one post. Im up to about 1,500 words. I will leave it here for now, and let interested folks who have read this far digest and ask any questions you may have.

One last thing this is very exciting stuff, and has many impacts beyond skin & aging. This is not mere cosmetics this is core cellular physiology. And how grand it is (for a change) that skin science gets to be on the forefront of research rather than on the back burner.

Await your comments.

Dr. John

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Stem Cells and Skin Part 3: It's the Cytokines ...

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The first iPS cell clinical trial insights – Stem Cell Assays

For an hour on Friday 12 September, Masayo Takahashi sat alone, calmly reflecting on the decade of research that had led up to this moment. (David Cyranoski, Nature doi:10.1038/516311a)

A year ago, the first historic transplantation of iPS cell-based product took place in Japan. Recently, the trial was halted due to RIKENs decision on changing strategy. Today, Id to summarize some new info about the first iPS cell trial, based on two recent articles.

Was treatment of the first patient safe and effective? Safe YES, as of 6 months post-transplant. One year safety report is coming soon. Some observations of potential efficacy were shared in todays issue of Cell & Gene Therapy Insights by Hardy Kagimoto (CEO of Healios KK):

She had a series of 18 anti-vascular endothelial growth factor (VEGF) ocular injections for both eyes to cope with the constant recurrence of the disease. The results presented by Dr Takahashi showed that, after the removal of the subretinal fibrotic tissue and implantation of the iPS-cell-derived retinal pigment epithelial (RPE) cell sheet, the patient experienced no recurrence of neovascularization at the 6 month point and was free from frequent anti-VEGF injections. Her visual acuity was stabilized and there have been no safety related concerns so far.

Mutations in the product from the 2nd patient Some mutations were detected in the iPS cell-derived RPE product, prepared for the second patient. Nobody knows if these mutations were prohibitive for product release, since nobody has a guidance. What we know about these mutations:

three single-nucleotide variations (SNVs) and three copy-number variants (CNVs) were present that were not detectable in the patients original fibroblasts. The CNVs were all single-gene deletions. With regards to the SNVs, one is listed in a curated database of cancer somatic mutations, but only linked to a single cancer, reports CiRA. The mutated genes were not driver genes for tumor formation, wrote Takahashi in an e-mail.

and more from Kagimotos piece:

The result of tumorigenicity testing has proven the final RPE cells to be safe. Furthermore, the presence of genetic mutation does not necessarily mean that these RPE cells can be tumorigenic.

Regulatory change As per trial PI, Masayo Takahashi, the main reason for trial halting was a regulatory change:

Although the mutations were identified before transplanting cells into the second patient, and the mutations may have contributed to RIKENs decision not to treat, the main reason not to go ahead with the trial was because of a regulatory change, says Takahashi.

New Japanese law on Regenerative Medicine became effective after iPS trial was started and after first product was transplanted. Perhaps, the trial design was not very suitable in this new regulatory framework. But still, there is no guidance in new regulation about allowable level of mutations and methods of their detection in iPS cell products:

there is no regulation with which medical professionals are obligated to check gene modification for organ transplantation, mesenchymal stem cell injections or autologous cell therapy. The fact remains that we do not have clear guidelines today on which the whole community can reach a consensus that the second RPE cells are safe enough for implantation .

RIKENs decision It seem to me RIKENs decision on halting a trial was wise and very strategic. The first and the most important thing here:

As a pioneer of iPS cell clinical application, Riken took the responsible decision not to rush ahead with the second patients RPE cells, which could potentially damage the whole field of regenerative medicine.

The second thing is if there is no guidance on mutations, why not develop it now?

Although therefore, the cells were widely thought to be safe to use, after careful consideration, they made the decision that they would not implant another autologous cell sheet until such guidelines could be officially authorized. They are now coordinating the discussions at the Ministry of Education, Culture, Sports, Science, and Technology, and also at the Ministry of Health, Labor and Welfare to carefully discuss these issues with key opinion leaders in the field including government officials, regulatory experts, scientists and toxicologists.

The third thing is realization that auto- model is not the way go in future:

As of now, autologous would not be a feasible way of providing wide level clinical therapy, says CiRA spokesperson Peter Karagiannis. At the experimental level its fine, but if its going to be mass produced or industrialized, it has to be allogeneic.

Moving forward So, RIKEN is moving forward with allo- iPS cell-derived RPE. Moving together with CiRA. Well characterized partially matched lines with safety clearance by rigorous QC testing. However, some concerns about potential immunogenicity were expressed by peers:

But the project is fraught with uncertainty, because HLA-matched cells might still suffer immune rejection. Were not going to know until those clinical trials, says Coffey. CiRA is not typing its cells for minor histocompatibility antigens, which can cause T cellmediated transplant rejection. The current effort is going for major [histocompatibility matching], says Kapil Bharti, a stem cell researcher at the National Eye Institute.

Expectations Im positive about future iPS cell-based trials. I like the approach, which RIKEN is taking. Here some of our expectation for the future (feel free to add to the list):

PS: Emphases throughout the text are mine.

Tagged as: clinical trial, genomic stability, iPS, iPS cell bank, safety, stem cell line, Takahashi M

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The first iPS cell clinical trial insights - Stem Cell Assays

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U.S. Public Opinion about Personalized Medicine Survey …

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Spinal Cord Injury – Spinal Cord Injury

Spinal Cord Injury Network - Spinal Cord Injury Network is one of the most comprehensive spinal cord injury website resources around. Find out everything you need to know about spinal cord injuries and paralysis all in one easy to access site. Listed below is a quick guide to spinal cord injury, everything is explained in much more detail inside the spinal cord injury network site

Spinal Cord Injury Spinal cord injury effects vary according to the type and level of spinal cord injury, and can be sorted into two main types:

In a complete spinal cord injury, there is no function below the "neurological" level, defined as the lowest level that has intact neurological function. If a person has some spinal injury level below which there is no motor and sensory function, the injury is said to be a complete spinal cord injury.

An incomplete spinal cord injury will retain some sensation or movement below the level of spinal cord injury. Incomplete spinal cord injuries may recover some walking ability. In addition to a loss of sensation and motor function below the point of spinal cord injury, individuals with spinal cord injuries will often experience other complications of spinal cord injury

A few Spinal Cord injury facts Spinal cord injury is relatively rare and estimated to affect between 35 to 65 people in every million population every year, Spinal cord injury is most prevalent in younger males aged 15 -35 The average age for spinal cord injury is 31 Spinal cord injury is most commonly caused by vehicle and sporting accidents You can have a spine injury including fractured or broken vertebrae without suffering a spinal cord injury. whiplash and falls can cause immediate symptoms of spinal cord injury which then diminish, whilst in these cases it is may be unlikely that any permanent spinal cord injury has happened its essential to seek medical advice Every year, about 2000 people in the UK suffer traumatic spinal cord injury leading to permanent paralysis. A cure for Spinal Cord Injury? It has been said since the end of the last century that spinal cord injury will eventually be repairable and that research looking at ways to restore function lost by spinal cord injury is showing promising signs, however to date there is no cure for spinal cord injury. When a spinal cord injury occurs The initial trauma can include both traction, which pulls nerve cells apart, and compression, which damages nerves and blood vessels. Nerve fibres that are detached from their cell nucleus must be rejoined within 4872 hours or function is lost forever

Compensation for Spinal Cord Injury?

Information and support can be found at this site for the following spinal cord injury subject areas:- spinal cord injury, spinal injury, spinal injuries, spinal cord injuries, spinal lesion, sci, tetraplegia, tetraplegic, quadraplegia, quadraplegic, quadriplegia, quadriplegic, paraplegia, paraplegic, paralysis, paralyzed, broken neck, broken back, break neck, break back, rehabilitation, spinal injury support groups, sci community, sci communities,

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Spinal Cord Injury - Spinal Cord Injury

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Spinal Cord Injury Facts & Statistics – sci-info-pages.com

Think you know the facts about spinal cord injuries? Here is some information that may surprise you.

According to the National Spinal Cord Injury Statistical Center at UAB, the distribution of the causes of SCI have changed drastically since 2010.

Researchers have estimated that, as of 2015, 12500 new SCI occur each year and between 240,000 and 337,000 people are currently living with SCI in the United States.

The average age at injury has moved from 29 years in the 1970's to 42 years in 2015.

The length of hospital stays is declining with the average stay in hospital acute care at 11 days - down from 24 in the 1970's - and rehabilitations stays at 36 days - down from 98 days in the 1970's.

Statistics and information provided by Panish Shea & Boyle.

Source: The University of Alabama National Spinal Cord Injury Statistical Center - March 2002

Although there is more information available about people who have a spinal cord injury than ever before, much of it is incomplete. Some of the statistical data is summarized below per 8/95.

32 injuries per million population or 7800 injuries in the US each year

Most researchers feel that these numbers represent significant under- reporting. Injuries not recorded include cases where the patient instantaneously or soon after the injury, cases with little or no remaining neurological deficit, and people who have neurologic problems secondary to trauma, but are not classified as SCI. Researchers estimate that an additional 20 cases per million (4860 per year) die before reaching the hospital.

People who return to work in the first year post-injury usually return to the same job for the same employer. People who return to work after the first year post-injury either worked for different employers or were students who found work.

Until the most recent figures were released by NSCIA in August,1995, these were considered as the major causes of spinal cord injuries. See Answer to # 4 and Dr. Wise Youngs statistics in Section 2 for allthe most recent demographics. One of the most surprising findings isthat acts of violence have now overtaken falls as the second mostcommon source of spinal cord injury, as of the 1995 findings.

Since 1988, 45% of all injuries have been complete, 55% incomplete. Complete injuries result in total loss of sensation and function below the injury level. Incomplete injuries result in partial loss. "Complete" does not necessarily mean the cord has been severed. Each of the above categories can occur in paraplegia and quadriplegia.

Except for the incomplete-Preserved motor (functional), no more than 0.9% fully recover, although all can improve from the initial diagnosis.

Overall, slightly more than 1/2 of all injuries result in quadriplegia. However, the proportion of quadriplegics increase markedly after age 45, comprising 2/3 of all injuries after age 60 and 87% of all injuries after age 75. 92% of all sports injuries result in quadriplegia.

Most people with neurologically complete lesions above C-3 die before receiving medical treatment. Those who survive are usually dependent on mechanical respirators to breathe.

50% of all cases have other injuries associated with the spinal cord injury.

Quadriplegia, incomplete 31.2% Paraplegia, complete 28.2% Paraplegia, incomplete 23.1% Quadriplegia, complete 17.5%

(Important: This section applies only to individuals who were admitted to one of the hospitals designated as "Model" SCI centers by the National Institute of Disability and Rehabilitation Research.)

Over 37% of all cases admitted to the Spinal Cord Injury System sponsored by the NIDRR arrive within 24 hours of injury. The mean time between injury and admission is 6 days.

Only 10-15% of all people with injuries are admitted to the NIDRR SCI system. The remainder go to CARF facilities or to general hospitals in their local community.

It is now known that the length of stay and hospital charges for acute care and initial rehabilitation are higher for cases where admission to the SCI system is delayed beyond 24 hours. Average length of stay (1992):

Quadriplegics 95 days Paraplegics 67 days All 79 days

Average charges (1990 dollars) Note: Specific cases are considerably higher.

Quadriplegics $118,900 Paraplegics $ 85,100 All $ 99,553

Source of payment acute care:

Private Insurance 53% Medicaid 25% Self-pay 1% Vocational Rehab 14% Worker's Comp 12% Medicare 5% Other 2%

Ongoing medical care: (Many people have more than one source of payment.)

Private Insurance 43% Medicare 25% Self-pay 2% Medicaid 31% Worker's Compensation 11% Vocational Rehab 16%

Residence at discharge

Private Residence 92% Nursing Home 4% Other Hospital 2% Group Home 2%

There is no apparent relationship between severity of injury and nursing home admission, indicating that admission is caused by other factors (i.e. family can't take care of person, medical complications, etc.) Nursing home admission is more common among elderly persons.

Each year 1/3 to 1/2 of all people with SCI are re-admitted to the hospital. There is no difference in the rate of re-admissions between persons with paraplegia and quadriplegia, but there is a difference between the rate for those with complete and incomplete injuries.

Overall, 85% of SCI patients who survive the first 24 hours are still alive 10 years later, compared with 98% of the non-SCI population given similar age and sex.

The most common cause of death is respiratory ailment, whereas, in the past it was renal failure. An increasing number of people with SCI are dying of unrelated causes such as cancer or cardiovascular disease, similar to that of the general population. Mortality rates are significantly higher during the first year after injury than during subsequent years.

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Spinal Cord Injury Facts & Statistics - sci-info-pages.com

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iPS cells and reprogramming: turn any cell of the body …

The discovery of iPS cells

In 2006, Shinya Yamanaka made a groundbreaking discovery that would win him the Nobel Prize in Physiology or Medicine just six years later: he found a new way to reprogramme adult, specialized cells to turn them into stem cells. These laboratory-grown stem cells are pluripotent they can make any type of cell in the body - and are called induced pluripotent stem cells, or iPS cells. Only embryonic stem cells are naturally pluripotent. Yamanakas discovery means that theoretically any dividing cell of the body can now be turned into a pluripotent stem cell.

So how are these iPS cells made? Yamanaka added four genes to skin cells from a mouse. This started a process inside the cells called reprogramming and, within 2 3 weeks, the skin cells were converted into induced pluripotent stem cells. Scientists can now also do this with human cells, by adding even fewer than four genes.

This short clip introduces the science behind reprogramming. View the full 16-minute film to see the whole story of Shinya Yamanaka's discovery.

IPS cells and embryonic stem cells are very similar. They are self-renewing, meaning they can divide and produce copies of themselves indefinitely. Both types of stem cell can be used to derive nearly any kind of specialized cell under precisely controlled conditions in the laboratory. Both iPS cells and embryonic stem cells can help us understand how specialized cells develop from pluripotent cells. In the future, they might also provide an unlimited supply of replacement cells and tissues for many patients with currently untreatable diseases.

In contrast to embryonic stem cells, making iPS cells doesnt depend on the use of cells from an early embryo. Are there any other differences? Current research indicates that some genes in iPS cells behave in a different way to those in embryonic stem cells. This is caused by incomplete reprogramming of the cells and/or genetic changes acquired by the iPS cells as they grow and multiply. Scientists are studying this in more detail to find out how such differences may affect the use of iPS cells in basic research and clinical applications. More research is also needed to understand just how reprogramming works inside the cell. So at the moment, most scientists believe we cant replace ES cells with iPS cells in basic research.

An important step in developing a therapy for a given disease is understanding exactly how the disease works: what exactly goes wrong in the body? To do this, researchers need to study the cells or tissues affected by the disease, but this is not always as simple as it sounds. For example, its almost impossible to obtain genuine brain cells from patients with Parkinsons disease, especially in the early stages of the disease before the patient is aware of any symptoms. Reprogramming means scientists can now get access to large numbers of the particular type of neurons (brain cells) that are affected by Parkinsons disease. Researchers first make iPS cells from, for example, skin biopsies from Parkinsons patients. They then use these iPS cells to produce neurons in the laboratory. The neurons have the same genetic background (the same basic genetic make-up) as the patients own cells. Thus scientist can directly work with neurons affected by Parkinsons disease in a dish. They can use these cells to learn more about what goes wrong inside the cells and why. Cellular disease models like these can also be used to search for and test new drugs to treat or protect patients against the disease.

Reprogramming holds great potential for new medical applications, such as cell replacement therapies. Since iPS cells can be made from a patients own skin, they could be used to grow specialized cells that exactly match the patient and would not be rejected by the immune system.If the patient has a genetic disease, the genetic problem could be corrected in their iPS cells in the laboratory, and these repaired iPS cells used to produce a patient-specific batch of healthy specialized cells for transplantation. But this benefit remains theoretical for now.

Until recently, making iPS cells involved permanent genetic changes inside the cell, which can cause tumours to form. Scientists have now developed methods for making iPS cells without this genetic modification. These new techniques are an important step towards making iPS-derived specialized cells that would be safe for use in patients. Further research is now needed to understand fully how reprogramming works and how iPS cells can be controlled and produced consistently enough to meet the high quality and safety requirements for use in the clinic.

Stem cells the future: an introduction to iPS cells Research into reprogrammed stem cells: an interactive timeline Stem cell school - multimedia learning module on cellular reprogramming Alzheimer Research Forum 4-part article on iPS cells and disease (September 2010) Nature news feature on challenges in the iPS field (May 2011) News article on the first iPS cell clinical trial (which is currently halted) Update on halted iPS cell clinical trial

This factsheet was created by Manal Hadenfeld, updated in 2012 by Michael Peitz and Annette Pusch and reviewed by Oliver Bruestle. Shinya Yamanaka photograph by Rubenstein. Additional images byMichael Peitz, Johannes Jungverdorben and Michael Rossbach.

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iPS cells and reprogramming: turn any cell of the body ...

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Personalized medicine: Precise genomic solutions for disease

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Genomics is what makes personalized medicine possible.

Personalized medicine is a new and better approach to health care based on each persons unique genetic makeup.

Personalized medicine, because it is based on each patients unique genetic makeup, is beginning to overcome the limitations of traditional...

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Personalized medicine: Precise genomic solutions for disease

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Stem Cell Therapy in India, Low Cost Stem Cell Therapy

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Stem cell therapy for heart failure: first implant of …

16.01.2015 - Press release

Circulation, metabolism, nutrition

On the 21 October 2014, Professor Philippe Menasch and his team from the cardiovascular surgery service of the Georges Pompidou European Hospital, AP-HP, carried out a transplant of cardiac cells derived from human embryonic stem cells*, according to a method developed by the Department of Cell and Tissue Biotherapies of the Saint-Louis hospital, directed by Professor Jrme Larghero and through research led by this group within Inserm. The surgery, coupled with a coronary bypass*, was carried out on a woman of 68 years suffering from severe heart failure. Ten weeks after the intervention, the patient is feeling well, her condition has improved markedly, with no complications having been observed. This promising advance was presented this Friday, 16 January 2015 at the XXV European Days Conference of the French Society of Cardiology.

Human embryonic stem cells. Transplantation of undifferentiated human embryonic stem cells into rat heart organotypic cultures. Presence of human cells, in the cardiac parenchyma of the rat two months after injection. The human cells are positive for human nuclear antigen marking (red). Cardiac rat tissue is positive for cardiac troponin 1 marking (green). I-Stem (Institiute for Stem Cell Therapy), Evry Genopole. Inserm/Habeler, Walter

The transplant was carried out as part of a clinical trial developed by the Public Hospitals of Paris (AP-HP) and through the work of the teams from AP-HP, Inserm and the universities of Paris-Descartes and Paris-Diderot. The cardiac cells were prepared according to a technique developed by the Department of Cell and Tissue Biotherapies of the Saint-Louis hospital. The cytogenetics laboratory of the Antoine Bclre Hospital and the French General Agency for Health Products and Equipment also contributed to the preparation of this phase I trial which will enable the verification of the safety and feasibility of the procedure

For 20 years Professor Menasch, currently co-director of an Inserm team within PARCC (Paris Centre for Cardiovascular Research), and his colleagues have been involved in stem cell* therapy for heart failure.

The team first tested the implant of skeletal muscle stem cells in necrosed areas of the heart in the laboratory. These cells were implanted into the heart of a patient with heart failure for the first time in the world on 15 June 2000. Following an initial series of these implants, always coupled with a coronary bypass, the team coordinated a European multi-centre, randomised, placebo-controlled trial whose results have still not been able to establish any significant benefit of these cells on the contractile function of patients hearts. One of the conclusions drawn from this trial was that to be fully efficient, transplanted cells should resemble the cells of the tissue to be repaired as much as possible, in this instance cardiac tissue. It was then decided to venture along the path of embryonic stem cells. Derived from embryos conceived in in vitro fertilisation, these cells do in fact possess pluripotent properties, that is, they are capable of developing into any type of cell of the body, including of course cardiac cells, as soon as they receive the appropriate signals during the culture cycle in the laboratory.

In 2007, the team then composed of, among others, Michel Pucat, Director of Research at Inserm, and Philippe Menasch showed that human embryonic stem cells could be differentiated into cardiac cells after being transplanted into the failing hearts of rats. Since then, many experiments have been carried out on different animal species in order to validate the efficacity of these cells and to optimise conditions which can guarantee maximum safety. At the end of this stage, a bank of pluripotent embryonic stem cells was formed in the conditions which satisfied all regulatory constraints applying to biological products for human use. Then, the Department of Cell and Tissue Biotherapies of the Saint-Louis hospital, still in liaison with the Inserm teams, developed and tested specialisation procedures for cells in order to produce young cardiac cells from them. The focus was then on the purification of the cells directed like so in order to ensure that the final product was expunged of any remaining pluripotent cells which could be potentially tumorigenic.

Besides, as initial experience with muscular stem cells showed the limitations of administering cells by multiple injections, their transfer is now performed using a patch that the cells are incorporated into. This patch is then placed on the area of the infarction. To that end, after the purification stage, the cardiac cells are incorporated into a circular fibrin gel which is applied, during the surgical procedure, to the necrosed area with just a few sutures ensuring that it is anchored to the cardiac tissue.

This type of surgery is aimed at serious heart failure which doesnt respond to the usual medicinal treatments but is not at the stage of a complete heart transplant. This is a promising advance, which we hope will enrich the therapeutic arsenal available to treat heart failure today explains Prof. Menasch. We are continuing the trial, which authorises us to carry out four other transplants. It would seem already that the benefits of the cells are linked mainly to the substances that they secrete. The direct administration of the substances, without going through a transplant of productive cells, is a path to explore.

This project has been entirely financed by funds from public intstitutions and societies and was authorised by the French National Agency for the Safety of Medicines and Health Products (ANSM) after agreement with the Agency for Biomedicine for the importation and research on human embryonic cells.

Cell therapy: refers to cell transplants aiming to restore the function of tissue or an organ when it has been altered by an accident, illness or ageing. These therapies have benefited from recent scientific advances on stem cells and give millions of patients the hope of regenerative medicine.

Embryonic or pluripotent stem cells: they can renew indefinitely (self-renewal), multiply in a culture and be differentiated into more than 200 types of cell. In the course of development, they are destined to form all types of the bodys tissue.

Coronary bypass: a technique that enables the redirection of the bloodstream towards the cardiac muscle, by using a graft (coming from the saphenous vein or from a thoracic artery.) One end of the graft is connected to the aorta, the main artery supplying the coronary arteries; the other end is connected to the coronary artery, situated just behind the site of the obstruction. This creates a detour enabling the oxygenated blood to circulate towards the heart.

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Biotechnology News — ScienceDaily

New Placenta Model Could Reveal How Birth Defect-Causing Infections Cross from Mom to Baby Mar. 4, 2016 Researchers have devised a cell-based model of the human placenta that could help explain how pathogens that cause birth defects cross from mother to unborn ... read more Mar. 3, 2016 Scientists have developed an animal model for breast cancer that faithfully captures the disease. Tested on human breast tissue, this the most clinically realistic model of breast cancer to ... read more Mar. 2, 2016 A faster, less expensive method has been developed and used to learn the DNA sequence of the male-specific Y chromosome in the gorilla. The research reveals that a male gorilla's Y chromosome is ... read more Mar. 2, 2016 DNA does not always adopt the form of the double helix which is associated with the genetic code; it can also form intricate folds and act as an enzyme: a deoxyribozyme. Scientists have solved the ... read more Mar. 2, 2016 Every cell in our bodies has its proper place, but how do they get there? A research group has discovered the mechanism for a mosaic pattern formation of two different cell types. Their discovery has ... read more Need for Better Characterized Genomes for Clinical Sequencing Mar. 1, 2016 Challenges in benchmarking difficult, but clinically important regions of the genome have been reported. The results underscore the need to extend benchmarking references against which sequencing ... read more A New Way to Stretch DNA Mar. 1, 2016 Researchers have recently developed a new way to controllably manipulate materials, in this case biomolecules that are too small to see with the naked eye. By stretching molecules like DNA and ... read more Mar. 1, 2016 This is a story about spit. Not just any spit, but the saliva of cyst nematodes, a parasite that literally sucks away billions in profits from soybean and other crops every year. Scientists find how ... read more Mar. 1, 2016 Our innate immune system uses two mechanisms. The first kills foreign bodies within the phagocyte itself. The second kills them outside the cell. Microbiologists have discovered that a social amoeba ... read more Preserved Siberian Moose With the DNA of Ancient Animal Discovered Mar. 1, 2016 Scientists have found preserved moose in Western Siberia that have unique features of DNA structure. This discovery will help determine the origin and path of moose movement in the last few tens of ... read more Unlocking the Secrets of Squid Sucker Ring Teeth Feb. 29, 2016 A squid has more in common with a spider than you may think. The razor-sharp 'teeth' that ring the suckers found on some squid tentacles are made up entirely of proteins remarkably similar ... read more Female Fertility Is Dependent on Functional Expression of the E3 Ubiquitin Ligase Itch Feb. 29, 2016 Protein ubiquitination is known to result in its proteasomal degradation or to serve as a signal for tissue-specific cellular functions. Here it is reported that mice with a mutant form of the E3 ... read more Cell Biology: Nuclear Export of Opioid Growth Factor Receptor Is CRM1 Dependent Feb. 29, 2016 The opioid growth factor receptor (OGFr) interacts with a specific opioid growth factor ligand (OGF), chemically termed [Met5]-enkephalin, to maintain homeostasis in a wide variety of normal and ... read more Feb. 29, 2016 DNA is made from four nucleosides, each known by its own letter -- A, G, C, and T. However, since the structure of DNA was deciphered in 1953, scientists have discovered several other variants that ... read more Feb. 29, 2016 Researchers have engineered microbes that can't run away from home. Any refugees that do quickly die without protective proteins produced by their peers. Dubbed 'swarmbots' for their ... read more Blood Vessels Sprout Under Pressure Feb. 29, 2016 It is blood pressure that drives the opening of small capillaries during angiogenesis. A team of researchers has observed the process for the first ... read more Feb. 29, 2016 A team of researchers has identified a new mechanism that regulates the effect of the satiety hormone leptin. The study identified the enzyme HDAC5 as key factor in our control of body weight and ... read more Making Better Enzymes and Protein Drugs Feb. 29, 2016 Natural selection results in protein sequences that are only soluble to the level that is required to carry out its physiological function. However, in biotechnological applications, we need these ... read more Feb. 29, 2016 The development of every animal in the history of the world began with a simple step: the fusion of a spermatozoon with an oocyte. Despite the ubiquity of this process, the actual mechanisms through ... read more Preventing Protein Unfolding Feb. 26, 2016 A computational model shows that polymers can reinforce proteins to prevent them from unfolding under mechanical ... read more

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Genetic Counseling – Genetics & IVF Institute

Decisions about family planning, genetic testing, and prenatal diagnosis are personal. Genetic counseling at the Genetics & IVF Institute is a process that will assist you in reaching a decision that is in the best interest of you and your family. Your genetic counselor will assist you in sorting through your medical information and all of the available choices. The goal of genetic counseling is to help you make an informed decision about your medical situation. Common reasons for genetic counseling include:

Depending on the complexity of your situation and the number of questions you have, genetic counseling sessions vary from 30 to 60 minutes in length. You will meet with a genetic counselor to review your family history, ethnicity, personal health, and pregnancy history. Analysis of this information allows the counselor to determine which, if any, tests would provide useful information for your reproductive and family planning.

All of your questions regarding the safety and accuracy of each testing option will be reviewed. The appropriateness of prenatal diagnosis, genetic screening, and other tests will vary, depending on your individual health and family history. The benefits and limitations of all the current testing options will be explained to you. Deciding to have a test done or deciding not to have a test done are both equally valid choices. If desired, testing can usually be done on the same day as your consultation, or you can choose to make an appointment for testing on a different day.

To schedule an appointment, click here or call 800.552.4363 or 703.698.7355.

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Genetic Counseling – kidshealth.org

If you and your partner are newly pregnant, you may be amazed at the number and variety of prenatal tests available to you. Blood tests, urine tests, monthly medical exams, screening tests, and family history tracking each helps to assess the health of you and your baby, and to predict any potential health risks.

You may also have the option of genetic testing. These tests identify the likelihood of passing certain genetic diseases or disorders (those caused by a defect in the genes the tiny, DNA-containing units of heredity that determine the characteristics and functioning of the entire body) to your children.

Some of the more familiar genetic disorders are:

If your history suggests that genetic testing would be helpful, you may be referred to a genetic counselor. Or, you might decide to seek out genetic counseling yourself.

But what do genetic counselors do, and how can they help your family?

Genetic counseling is the process of:

Genetic tests are done by analyzing small samples of blood or body tissues. They determine whether you, your partner, or your baby carry genes for certain inherited disorders.

Genes are made up of DNA molecules, which are the building blocks of heredity. They're grouped together in specific patterns within a person's chromosomes, forming the unique "blueprint" for every physical and biological characteristic of that person.

Humans have 46 chromosomes, arranged in pairs in every living cell of our bodies. When the egg and sperm join at conception, half of each chromosomal pair is inherited from each parent. This newly formed combination of chromosomes then copies itself again and again during fetal growth and development, passing identical genetic information to each new cell in the growing fetus.

Current science suggests that every human has about 25,000 genes per cell. An error in just one gene (and in some instances, even the alteration of a single piece of DNA) can sometimes be the cause for a serious medical condition.

Some diseases, such as Huntington's disease (a degenerative nerve disease) and Marfan syndrome (a connective tissue disorder), can be inherited from just one parent. But most disorders, includingcystic fibrosis, sickle cell anemia, and Tay-Sachs disease, cannot occur unless both the mother and father pass along the gene.

Other genetic conditions, such as Down syndrome, are usually not inherited. In general, they result from an error (mutation) in the cell division process during conception or fetal development. Still others, such as achondroplasia (the most common form of dwarfism), may either be inherited or the result of a genetic mutation.

Genetic tests don't yield easy-to-understand results. They can reveal the presence, absence, or malformation of genes or chromosomes. Deciphering what these complex tests mean is where a genetic counselor comes in.

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Personalized Medicine News — ScienceDaily

Nano Dangerously Big Feb. 23, 2016 Keywords such as nano-, personalized-, or targeted medicine sound like bright future. What most people do not know, is that nanomedicines can cause severe undesired effects for actually being too ... read more Unique Next Generation Sequencing-Based Panel Designed for Pediatric Cancer Research Feb. 18, 2016 A next-generation sequencing (NGS)-based panel will be designed specifically for pediatric cancer research, say scientists. The assay would be designed to target biomarkers associated with childhood ... read more Study Pinpoints Driver, Potential Target in Aggressive Pediatric Leukemia Subtype Feb. 18, 2016 Scientists report that they have discovered inactivation of the gene EZH2 as a driver and inroad to a potential therapeutic target in aggressive pediatric leukemia ... read more Feb. 15, 2016 Scientists have concluded a study of how inherited genetic variations in the NUDT15 gene cause serious chemotherapy toxicity; findings point to potential genetics-guided precision ... read more Feb. 10, 2016 A cardio-oncology program is focusing on modulating the risk factors for cardiovascular disease in men, especially those receiving androgen deprivation therapy (ADT) to treat their prostate ... read more Professors Use Cadaver DNA to Advance Genetics Literacy in Medical Curricula Feb. 9, 2016 Cadavers have long been one of the most important resources for anatomy teaching in medical school. Now, they are also at the forefront of cutting-edge genetics teaching, thanks to some innovative ... read more Proteomics and Precision Medicine Feb. 5, 2016 Researchers have used personalized proteomics to devise a successful treatment strategy for a patient with uveitis, a potentially blinding eye disease that can have many causes, making it ... read more Single-Lesion Biopsy May Be Insufficient to Choose Therapy Targeting Resistance Mutations Feb. 5, 2016 When metastatic tumors driven by drug-targetable genetic mutations become resistant to a targeted therapy drug, the usual practice is to test a single metastatic lesion for new mutations that can ... read more Researchers Patent New Methods That Allow Them to Identify the Cells Causing Metastasis in Cancer Feb. 4, 2016 Researchers have patented a new method that allows to identify the cells causing metastasis in cancer, with a simple blood ... read more Making the Leap from Sequence Data to Actionable Targets in Clinical Oncology Feb. 1, 2016 The ever-shrinking cost of DNA sequencing improves accessibility for an increasing number of people and, importantly, for the diagnosis and treatment of disease. This is particularly salient in ... read more Jan. 28, 2016 Clinical genomic sequencing is feasible in pediatric oncology and can be used to recommend therapy or pinpoint diagnosis in children with solid tumors, according to the multi-center ... read more In Lung Cancer, Not All HER2 Alterations Are Created Equal Jan. 28, 2016 Study shows two distinct causes of HER2 activation in lung cancer: mutation of the gene and amplification of the gene. In patient samples of lung adenocarcinoma, 3 percent were found to have HER2 ... read more Test Rapidly, Accurately Profiles Genetics and Treatment of Brain Tumors Jan. 27, 2016 Brain tumors can be rapidly and accurately profiled with a next-generation, gene-sequencing test recently developed. The test, called GlioSeq, is now being used by oncologists to help guide treatment ... read more Disclosure of Incidental Genetic Findings Can Have Positive Impact for Patients Jan. 26, 2016 Providing unanticipated information about risk of coronary artery disease during a genetic risk assessment for Alzheimer's disease helped some participants cope with their results, and also ... read more Inherited Genetic Markers May Predict Melanoma Survival -- And Help Plot Course of Disease Jan. 20, 2016 How long will a patient survive following the removal of a melanoma tumor? A more definitive answer to that question could come from new studies. Researchers there have discovered an inherited ... read more Important Associations Between Genetics, Sleep Behavior Identified by Study Jan. 12, 2016 A research initiative exploring the utility of genetic information in the clinical setting has published a study and identified six noteworthy genes that affect human sleep duration. The focus of the ... read more Epigenetic Regulation of Metastatic Breast Cancer Progression May Guide Prognosis, Future Therapy Jan. 7, 2016 A gene that plays a role in the development of breast cancer to metastatic disease has been identified which may help to predict disease progression and serve as a target for the development of ... read more New Approach to Diagnosing Low Back Pain, Revealed by Clinical Study Jan. 7, 2016 A new, personalized approach to diagnosing low back pain has been discovered by researchers. Low back pain is the second most common cause of physician visits in the US and contributes to an ... read more Lung Cancer Clinical Trial Finds Lung Function Without Additional Imaging Jan. 6, 2016 A clinical trial is evaluating a new method for pinpointing and sparing healthy lung tissue during lung cancer radiotherapy. The group is applying advanced image analysis techniques to 4D CT scans ... read more Jan. 6, 2016 Researchers have found the 'bad seeds' of liver cancer and believe they could one day reprogram them to remain responsive to cancer treatment, a new study has found. The key to disrupting ... read more

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Personalized Medicine: How the Human Genome Era Will Usher …

Personalized Medicine: How the Human Genome Era Will Usher in a Health Care Revolution

Personalized medicine has the potential to transform healthcare through earlier diagnosis, more effective prevention and treatment of disease, and avoidance of drug side effects. The challenge for policymakers will be to deal intelligently and comprehensively with the array of issues that will affect quality of healthcare under this new paradigm.

On February 10, 2005, NHGRI Director Dr. Francis Collins, the senior advisor on genomics in the Federal government, outlined his vision for the future of genomics-based medicine to the Personalized Medicine Coalition (PMC) at the National Press Club. He also explored the numerous policy issues that must be addressed to realize the full potential of this new area of medicine.

To view the integrated presentation of both video and Power Point slides, go to:

For Web browsers other than IE or Netscape, go to the lecture webcast on the PMC Web site at:

Last Updated: March 17, 2012

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Personalized Medicine: How the Human Genome Era Will Usher ...

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Medical Technology IPS Cell Therapy IPS Cell Therapy

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Stem Cell Therapy | Stanford Initiative to Cure Hearing Loss

What if doctors could grow a new working inner ear from a persons own skin cells? Or repair the damaged inner ear from within?

Solving this profound mystery is the driving force behind stem cell research and the promise of tissue engineering in otolaryngology. While hearing aids and cochlear implants can provide good recovery of hearing function, the development of a biological method to repair the damaged cochlea has the potential to restore normal hearing without any type of prosthesis.

One approach to restore hearing might be to surgically place stem cells within the cochlea in such a way that they would fuse with the remaining cochlear structures and develop and function as hair cells. Scientists believe this is a viable approach because, unlike most organs that are destroyed by disease, the inner ear remains structurally intactonly the hair cells are lost. By mimicking the steps involved in the formation of embryonic mouse ears, Stanford scientists have produced stem cells in the laboratory that look and act very much like hair cells, the sensory cells that normally reside in the inner ear. If they can generate hair cells in the millions, it could lead to significant scientific and clinical advances along the path to curing deafness in the future.

A promising source of creating hair cells comes from induced pluripotent stem cells (iPS)adult cells, taken for example from a patients own skin that have been genetically reprogrammed to revert back to stem cells. This breakthrough process represents a major opportunity to eventually treat a patient with his or her own cells.

Currently, our research team is working toward producing human hair cells for the first time in a culture dish. This work could lead, in the long run, to novel therapies based on cell transplantation.

Equally exciting is an ongoing approach to use embryonic stem cell-based approaches for discovery of novel drugs that could be used for treatment for deafness. More about this exciting new direction can be found under Molecular Therapy.

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Spinal Cord Injury – Conditions – For Patients …

Spinal Cord Injury

For more information, please visit our Integrated Spine Care site

The spinal cord is a bundle of nerves that carries messages between the brain and the rest of the body.

Acute spinal cord injury (SCI) is due to a traumatic injury that can either result in a bruise (also called a contusion), a partial tear, or a complete tear (called a transection) in the spinal cord. About 250,000 to 400,000 individuals in the US have a spinal cord injury. About 60 percent of these cases are 30 years old or younger.

The annual incidence of spinal cord injury in the U.S. is 40 cases per million, or 12,000 new cases each year. The number of people in the U.S. in 2008 living with a spinal cord injury is approximately 259,000, with a range of 229,000 to 306,000.

SCI results in a decreased or absence of movement, sensation, and body organ function below the level of the injury. The most common sites of injury are the cervical and thoracic areas. SCI is a common cause of permanent disability and death in children and adults.

The spine consists of 33 vertebrae, including the following:

* By adulthood, the 5 sacral vertebrae fuse to form one bone, and the 4 coccygeal vertebrae fuse to form one bone.)

These vertebrae function to stabilize the spine and protect the spinal cord. In general, the higher in the spinal column the injury occurs, the more dysfunction a person will have.

Injury to the vertebrae does not always mean the spinal cord has been damaged. Likewise, damage to the spinal cord itself can occur without fractures or dislocations of the vertebrae.

There are many causes of SCI. The more common injuries occur when the area of the spine or neck is bent or compressed, as in the following:

Penetrating injuries that pierce the cord, such as gunshots and stab wounds may also cause damage.

Symptoms vary depending on the severity and location of the SCI. At first, the patient may experience spinal shock, which causes loss of feeling, muscle movement, and reflexes below the level of injury. Spinal shock usually lasts from several hours to several weeks. As the period of shock subsides, other symptoms appear, depending on the location of the injury.

Generally, the higher up the level of the injury to the spinal cord, the more severe the symptoms. For example, an injury at C2 or C3 (the second and third vertebrae in the spinal column), affects the respiratory muscles and the ability to breathe. A lower injury, in the lumbar vertebrae, may affect nerve and muscle control to the bladder, bowel, and legs.

The following are the most common symptoms of acute spinal cord injuries. However, each individual may experience symptoms differently.

Symptoms may include:

The symptoms of SCI may resemble other medical conditions or problems. Always consult your physician for a diagnosis.

The following chart is a comparison of the specific level of SCI and the resulting rehabilitation potential. This chart is a guide, with general information only; impairments and rehabilitation potential can vary depending on the type and severity of SCI. Always consult your physician for more specific information based on your individual medical condition and injury.

Rehabilitation of the patient with a SCI begins during the acute treatment phase. As the patient's condition improves, a more extensive rehabilitation program is often begun.

The success of rehabilitation depends on many variables, including the following:

It is important to focus on maximizing the patient's capabilities at home and in the community. Positive reinforcement helps recovery by improving self-esteem and promoting independence.

The goal of SCI rehabilitation is to help the patient return to the highest level of function and independence possible, while improving the overall quality of life - physically, emotionally, and socially.

Areas covered in spinal cord injury rehabilitation programs may include:

The spinal cord injury rehabilitation team revolves around the patient and family and helps set short-and long-term treatment goals for recovery. Many skilled professionals are part of the spinal cord injury rehabilitation team, including any/all of the following:

There are a variety of spinal cord injury treatment programs, including the following:

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Spinal Cord Injury - Conditions - For Patients ...

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Personalized Medicine – NIH News in Health, December 2013

Youre one of a kind. Its not just your eyes, smile, and personality. Your health, risk for disease, and the ways you respond to medicines are also unique. Medicines that work well for some people may not help you at all. They might even cause problems. Wouldnt it be nice if treatments and preventive care could be designed just for you?

The careful matching of your biology to your medical care is known as personalized medicine. Its already being used by health care providers nationwide.

The story of personalized medicine begins with the unique set of genes you inherited from your parents. Genes are stretches of DNA that serve as a sort of instruction manual telling your body how to make the proteins and perform the other tasks that your body needs. These genetic instructions are written in varying patterns of only 4 different chemical letters, or bases.

The same genes often differ slightly between people. Bases may be switched, missing, or added here and there. Most of these variations have no effect on your health. But some can create unusual proteins that might boost your risk for certain diseases. Some variants can affect how well a medicine works in your body. Or they might cause a medicine to have different side effects in you than in someone else.

The study of how genes affect the way medicines work in your body is called pharmacogenomics.

If doctors know your genes, they can predict drug response and incorporate this information into the medical decisions they make, says Dr. Rochelle Long, a pharmacogenomics expert at NIH.

Its becoming more common for doctors to test for gene variants before prescribing certain drugs. For example, children with leukemia might get the TPMT gene test to help doctors choose the right dosage of medicine to prevent toxic side effects. Some HIV-infected patients are severely allergic to treatment drugs, and genetic tests can help identify who can safely take the medicines.

By screening to know who shouldnt get certain drugs, we can prevent life-threatening side effects, Long says.

Pharmacogenomics is also being used for cancer treatment. Some breast cancer drugs only work in women with particular genetic variations. If testing shows patients with advanced melanoma (skin cancer) have certain variants, 2 new approved drugs can treat them.

Even one of the oldest and most common drugs, aspirin, can have varying effects based on your genes. Millions of people take a daily aspirin to lower their risk for heart attack and stroke. Aspirin helps by preventing blood clots that could clog arteries. But aspirin doesnt reduce heart disease risk in everyone.

NIH-funded researchers recently identified a set of genes with unique activity patterns that can help assess whether someone will benefit from taking aspirin for heart health. Scientists are now working to develop a standardized test for use in daily practice. If doctors can tell that aspirin wont work in certain patients, they can try different treatments.

One NIH-funded research team studied a different clot-fighting drug known as clopidogrel (Plavix). Its often prescribed for people at risk for heart attack or stroke. Led by Dr. Alan Shuldiner at the University of Maryland School of Medicine, the team examined people in an Amish community. Isolated communities like this have less genetic diversity than the general population, which can make it easier to study the effects of genes. But as in the general population, some Amish people have risk factors, such as eating a high-fat diet, that raise their risk for heart disease.

Many of the Amish people studied had a particular gene variant that made them less responsive to clopidogrel, the scientists found. Further research revealed that up to one-third of the general population may have similar variations in this gene, meaning they too probably need a different medicine to reduce heart disease risks.

The findings prompted the U.S. Food and Drug Administration (FDA) to change the label for this common drug to alert doctors that it may not be appropriate for patients who have certain gene variations. Two alternative drugs have since been developed. If people have these gene variants, they know they have options, says Shuldiner. This is a great example of how study results made it onto a drug label and are beginning to be implemented into patient care.

Getting a genetic test usually isnt difficult. Doctors generally take a sample of body fluid or tissue, such as blood, saliva or skin, and send it to a lab. Most genetic tests used today analyze just one or a few genes, often to help diagnose disease. Newborns, for example, are routinely screened for several genetic disorders by taking a few drops of blood from their heels. When life-threatening conditions are caught early, infants can be treated right away to prevent problems.

The decision about whether to get a particular genetic test can be complicated. Genetic tests are now available for about 2,500 diseases, and that number keeps growing. Your doctor might advise you to get tested for specific genetic diseases if they tend to run in your family or if you have certain symptoms.

While there are many genetic tests, they vary as to how well they predict risk, says Dr. Lawrence Brody, a genetic testing expert at NIH.

For some diseases, such as sickle cell anemia or cystic fibrosis, inheriting 2 copies of abnormal genes means a person will get that disease. But for other diseases and conditions, the picture is more complex. For type 2 diabetes, testing positive for some specific gene variants may help predict risk, but no better than other factorssuch as obesity, high blood pressure and having a close relative with the disease.

The latest approach to personalized medicine is to get your whole sequenced. Thats still expensive, but the cost has dropped dramatically over the past decade and will likely continue to fall. Since your genome essentially stays the same over time, this information might one day become part of your medical record, so doctors could consult it as needed.

You can start to get a sense of your genetic risks by putting together your familys health history. A free online tool called My Family Health Portrait from the U.S. Surgeon General can help you and your doctor spot early warning signs of conditions that run in your family.

But personalized medicine isnt just about genes. You can learn a lot about your health risks by taking a close look at your current health and habits. Smoking, a poor diet, and lack of exercise can raise your risks for life-threatening health problems, such as heart disease and cancer. Talk to your health care provider about the steps you can take to understand and reduce your unique health risks.

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Personalized Medicine - NIH News in Health, December 2013

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Genetic Counseling and Risk Assessment: The LIFE Center …

About the LIFE Center

The LPGA prosIn the Fight to Eradicate breast cancer (LIFE) Center at the Cancer Institute of New Jersey is dedicated to teaching young women how to maintain breast health and reduce the factors that increase their risk of breast cancer.The Center was establishedto recognize the support and advocacy of professional golfer, Val Skinner who is the founder of the Val Skinner Foundationand LIFE, and the LPGApros. The LIFE Center is a place where young women can come to better understand their personal risk to develop cancer and what they can do about it. The LIFE Center is positioned to identify and meet the needs of young women of diverse cultures and ethnicities. Researchers and medical professionals at The LIFE Center are dedicated to improving young women's understanding of their risk to develop breast cancer and their knowledge of appropriate prevention and screening strategies.

The Hereditary Oncology Prevention and Evaluation (HOPE) program is funded by and located within the LIFE Center. The program is designed for iindividuals who are concerned about their risks to develop cancer based on his or her family history of cancer, or his or her own personal medical history. The program offers patients and families appropriate medical and genetic testing information, and provides support and resources for those confronting cancer risk. The aim of the HOPE program is to help patients and families make informed decisions about their own health care as well as to provide information about ways to monitor for and treat possible cancer.

The LIFE Center and HOPE program are directed by Dr. Deborah Toppmeyer, and include a group of specialists who provide comprehensive care to families and individuals concerned about their risks of developing cancer. Your multidisciplinary team may include a genetic counselor, medical oncologist, surgical oncologist, gynecologist, and/or social worker. With the multiple perspectives of a multidisciplinary team, the HOPE program is able to address many of the unique needs of high-risk cancer patients and families.

The Hereditary Oncology Prevention and Evaluation (HOPE) Program is designed for anyone who is worried about his or her own personal cancer risk or about cancer within the family.

It is especially helpful for families with any of the following:

Genetic Testing When family history is suggestive of an inherited cancer risk, genetic testing may be available to further define your own risk of cancer as well as the risk to your relatives. If available and recommended, genetic testing will be offered at the conclusion of you initial appointment with the HOPE program

Follow-up Plan Based on the teams risk assessment, a personalized plan for careful monitoring and/or prevention will be designed and provided to you and your doctors. You may also choose to continue to be seen at our center.

Psychosocial Support Social workers and genetic counselors will be available to help you and your family address the unique issues involved with assessment and management of cancer risk.

Research You will have access to appropriate clinical studies to evaluate new methods for the early detection of cancer, cancer prevention, cancer treatment, and genetic testing. Eligibility, benefits and limitations of these trials will be discussed, when appropriate.

Additional Resources The LIFE Center and HOPE program have several ongoing initiatives to promote genetic counseling services throughout the community as well as to provide ongoing support and education to patients of the program.

The primary location of the Hereditary Oncology Prevention and Evaluation (HOPE) Program is in the LIFE Center at the Cancer Institute of New Jersey in New Brunswick, NJ. However, CINJ, the LIFE Center, and the HOPE Program strive to provide the best cancer care throughout the community. To achieve this goal, genetic counselors from the HOPE Program visit multiple outreach clinics throughout New Jersey at CINJaffiliate hospitalsto provide genetic counseling services to community hospitals.

Deborah Toppmeyer, MD, Director, Medical Oncologist Hetal Vig, MS, CGC, Genetic Counselor Stephanie Pachter, MS, CGC, Genetic Counselor Sandra D'Elia, MS, CGC, Genetic Counselor Sarah Nashed, MS, CGC, Genetic Counselor

How to schedule an appointment or get more information

To schedule an appointment or for further information, please call 732-235-7110 or email us at hope_program@cinj.rutgers.edu.

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