Archive for the ‘Skin Stem Cells’ Category

ScienceDaily (Mar. 22, 2012) Breaking new ground, scientists at the Max Planck Institute for Molecular Biomedicine in Mnster, Germany, have succeeded in obtaining somatic stem cells from fully differentiated somatic cells. Stem cell researcher Hans Schler and his team took skin cells from mice and, using a unique combination of growth factors while ensuring appropriate culturing conditions, have managed to induce the cells' differentiation into neuronal somatic stem cells.

"Our research shows that reprogramming somatic cells does not require passing through a pluripotent stage," explains Schler. "Thanks to this new approach, tissue regeneration is becoming a more streamlined -- and safer -- process."

Up until now, pluripotent stem cells were considered the 'be-all and end-all' of stem cell science. Historically, researchers have obtained these 'jack-of-all-trades' cells from fully differentiated somatic cells. Given the proper environmental cues, pluripotent stem cells are capable of differentiating into every type of cell in the body, but their pluripotency also holds certain disadvantages, which preclude their widespread application in medicine. According to Schler, "pluripotent stem cells exhibit such a high degree of plasticity that under the wrong circumstances they may form tumours instead of regenerating a tissue or an organ." Schler's somatic stem cells offer a way out of this dilemma: they are 'only' multipotent, which means that they cannot give rise to all cell types but merely to a select subset of them -- in this case, a type of cell found in neural tissue -- a property, which affords them an edge in terms of their therapeutic potential.

To allow them to interconvert somatic cells into somatic stem cells, the Max Planck researchers cleverly combined a number of different growth factors, proteins that guide cellular growth. "One factor in particular, called Brn4, which had never been used before in this type of research, turned out to be a genuine 'captain' who very quickly and efficiently took command of his ship -- the skin cell -- guiding it in the right direction so that it could be converted into a neuronal somatic stem cell," explains Schler. This interconversion turns out to be even more effective if the cells, stimulated by growth factors and exposed to just the right environmental conditions, divide more frequently. "Gradually, the cells lose their molecular memory that they were once skin cells," explains Schler. It seems that even after only a few cycles of cell division the newly produced neuronal somatic stem cells are practically indistinguishable from stem cells normally found in the tissue.

Schler's findings suggest that these cells hold great long-term medical potential: "The fact that these cells are multipotent dramatically reduces the risk of neoplasm formation, which means that in the not-too-distant future they could be used to regenerate tissues damaged or destroyed by disease or old age; until we get to that point, substantial research efforts will have to be made." So far, insights are based on experiments using murine skin cells; the next steps now are to perform the same experiments using actual human cells. In addition, it is imperative that the stem cells' long-term behaviour is thoroughly characterized to determine whether they retain their stability over long periods of time.

"Our discoveries are a testament to the unparalleled degree of rigor of research conducted here at the Mnster Institute," says Schler. "We should realize that this is our chance to be instrumental in helping shape the future of medicine." At this point, the project is still in its initial, basic science stage although "through systematic, continued development in close collaboration with the pharmaceutical industry, the transition from the basic to the applied sciences could be hugely successful, for this as well as for other, related, future projects," emphasizes Schler. This, then, is the reason why a suitable infrastructure framework must be created now rather than later. "The blueprints for this framework are all prepped and ready to go -- all we need now are for the right political measures to be ratified to pave the way towards medical applicability."

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by Max-Planck-Gesellschaft.

Read more here:
Somatic stem cells obtained from skin cells; pluripotency 'detour' skipped

"Our research shows that reprogramming somatic cells does not require passing through a pluripotent stage," explains Schler. "Thanks to this new approach, tissue regeneration is becoming a more streamlined - and safer - process."

Up until now, pluripotent stem cells were considered the 'be-all and end-all' of stem cell science. Historically, researchers have obtained these 'jack-of-all-trades' cells from fully differentiated somatic cells. Given the proper environmental cues, pluripotent stem cells are capable of differentiating into every type of cell in the body, but their pluripotency also holds certain disadvantages, which preclude their widespread application in medicine. According to Schler, "pluripotent stem cells exhibit such a high degree of plasticity that under the wrong circumstances they may form tumours instead of regenerating a tissue or an organ." Schler's somatic stem cells offer a way out of this dilemma: they are 'only' multipotent, which means that they cannot give rise to all cell types but merely to a select subset of them - in this case, a type of cell found in neural tissue - a property, which affords them an edge in terms of their therapeutic potential.

To allow them to interconvert somatic cells into somatic stem cells, the Max Planck researchers cleverly combined a number of different growth factors, proteins that guide cellular growth. "One factor in particular, called Brn4, which had never been used before in this type of research, turned out to be a genuine 'captain' who very quickly and efficiently took command of his ship - the skin cell - guiding it in the right direction so that it could be converted into a neuronal somatic stem cell," explains Schler. This interconversion turns out to be even more effective if the cells, stimulated by growth factors and exposed to just the right environmental conditions, divide more frequently. "Gradually, the cells lose their molecular memory that they were once skin cells," explains Schler. It seems that even after only a few cycles of cell division the newly produced neuronal somatic stem cells are practically indistinguishable from stem cells normally found in the tissue.

Schler's findings suggest that these cells hold great long-term medical potential: "The fact that these cells are multipotent dramatically reduces the risk of neoplasm formation, which means that in the not-too-distant future they could be used to regenerate tissues damaged or destroyed by disease or old age; until we get to that point, substantial research efforts will have to be made." So far, insights are based on experiments using murine skin cells; the next steps now are to perform the same experiments using actual human cells. In addition, it is imperative that the stem cells' long-term behaviour is thoroughly characterized to determine whether they retain their stability over long periods of time.

"Our discoveries are a testament to the unparalleled degree of rigor of research conducted here at the Mnster Institute," says Schler. "We should realize that this is our chance to be instrumental in helping shape the future of medicine." At this point, the project is still in its initial, basic science stage although "through systematic, continued development in close collaboration with the pharmaceutical industry, the transition from the basic to the applied sciences could be hugely successful, for this as well as for other, related, future projects," emphasizes Schler. This, then, is the reason why a suitable infrastructure framework must be created now rather than later. "The blueprints for this framework are all prepped and ready to go - all we need now are for the right political measures to be ratified to pave the way towards medical applicability."

More information: Han D.W., Tapia N., Hermann A., Hemmer K., Hing S., Arazo-Bravo M.J., Zaehres H., Frank S., Moritz S., Greber B., Yang J.H., Lee H.T., Schwamborn J.C., Storch A., Schler H.R. (2012) Direct Reprogramming of Fibroblasts into Neural Stem Cells by Defined Factors, Cell Stem Cell, CELL-STEM-CELL-D-11-00679R3

Provided by Max-Planck-Gesellschaft (news : web)

Go here to read the rest:
Somatic stem cells obtained from skin cells for first time ever

Scientists in SA have generated non-embryonic stem cells for the first time, the Council for Scientific and Industrial Research (CSIR) announced on Tuesday.

These "induced adult pluripotent stem cells" were developed from adult skin cells and can be prompted to grow into any type of adult cell, such as those in the heart or brain.

The technology is important for research into regenerative medicine, but is not yet widely used.

While the technology is not novel, the development of the capacity to grow these stem cells in SA is important for researchers investigating diseases affecting Africans, said CSIR post-doctoral fellow Janine Scholefield. The CSIR had replicated techniques devised by Japanese researchers in 2007.

"Cutting-edge medical research is not useful to Africans if knowledge is being created and applied only in the developed world," said CSIR head of gene expression and biophysics Musa Mhlanga. "Given the high disease burden in Africa, our aim is to become creators of knowledge, as well as innovators and expert practitioners of the newest and best technologies," The CSIR said that adult-generated stem cells were more acceptable to people who objected to using stem cells from embryos.

"The other critical thing is the cells (that will be grown) are an exact genetic match to the person who donated the skin cells, so we can circumvent the problem of tissue rejection," Dr Scholefield said.

"We can also develop models of disease in a petri dish in the laboratory," she said, explaining that this would enable researchers to investigate rare diseases without the need for human subjects.

"We are getting closer to using stem cells as part of routine medical practice, but are still a long way off from using these cells for degenerative diseases of the central nervous system," said Michael Pepper, professor of i mmunology at the University of Pretoria.

Prof Pepper said there were several hundred clinical trials using stem cells under way around the world, but most were still at an early stage.

Read this article:
SA cracks stem cell conundrum

CARLSBAD, Calif.--(BUSINESS WIRE)--

International Stem Cell Corporation (OTCBB: ISCO.OB - News) (www.internationalstemcell.com) today announced year-end financial results for the year ended December 31, 2011. ISCO is a California-based development-stage biotechnology company that is focused on therapeutic, biomedical and cosmeceutical product development and commercialization with multiple long-term therapeutic opportunities and two revenue-generating businesses offering potential for increased future revenue.

ISCO reported revenue of $1.1 million for the fourth quarter ended December 31, 2011, reflecting a 110% increase from the same period of the prior year. For the twelve months ended December 31, 2011, the Company reported revenue of $4.5 million, reflecting a year-over-year increase of 189%. The increases in revenues in both periods were primarily driven by strong sales at ISCOs wholly-owned subsidiary Lifeline Skin Care (LSC). In addition, steady growth in sales from ISCOs other wholly-owned subsidiary, Lifeline Cell Technology (LCT), contributed to the increases in revenues for both periods.

While the Company continued to invest in therapeutic projects, development of new technologies, and expansion of products and channels of distribution, to date we have generated limited revenue to support our core therapeutic research and development efforts. For the three months ended December 31, 2011, development expenses, excluding cost of sales, increased $507,000 or 17% compared with the same period of 2010, a reflection of increased G&A expenses resulting from higher stock-based compensation expenses.

For the twelve months ended December 31, 2011, development expenses, excluding costs of sales, increased approximately $3.0 million or 26% when compared with the prior year period.The majority of the increase was primarily due to increases in general and administrative and research and development activities. General and administrative expenses increased largely due to increased non-cash stock-based compensation, higher headcount, and increased expenses related business development activity and general corporate expenses. Research & Development expenses increased mainly due to increased number and complexity of experiments associated with our scientific projects. The increase in development expenses was also related to increased research activities on therapeutic products and product research activities for LSC and LCT coupled with increased sales and marketing expenses related to our skin care products.

Some of the 2011 Highlights:

-- A number of donors willing to provide oocytes for research purposed were enrolled in ISCO's program to establish a bank of clinical grade hpSC capable of being immune-matched to millions of patients.

-- The Research and Development team successfully completed the first series of preclinical studies that supports the therapeutic use of hepatocytes (liver cells) and neuronal cells derived from human parthenogenetic stem cells (hpSC). These in vivo experiments demonstrated that the derived cells are able to survive in targeted locations in mice without causing tumors.

-- We became Sarbanes-Oxley compliant and maintained, in all material respects, effective internal controls over financial reporting as of December 31, 2011.

-- We strengthened our Management Team through the appointments of well-known industry executives: Kurt May as President & Chief Operating Officer, Linh Nguyen as Chief Financial Officer, Donna Queen as Vice President of Marketing and Business Development for LSC.

Follow this link:
International Stem Cell Corporation Announces 2011 Financial Results

CARLSBAD, Calif.--(BUSINESS WIRE)--

International Stem Cell Corporation (OTCBB: ISCO.OB - News) (www.internationalstemcell.com) today announced year-end financial results for the year ended December 31, 2011. ISCO is a California-based development-stage biotechnology company that is focused on therapeutic, biomedical and cosmeceutical product development and commercialization with multiple long-term therapeutic opportunities and two revenue-generating businesses offering potential for increased future revenue.

ISCO reported revenue of $1.1 million for the fourth quarter ended December 31, 2011, reflecting a 110% increase from the same period of the prior year. For the twelve months ended December 31, 2011, the Company reported revenue of $4.5 million, reflecting a year-over-year increase of 189%. The increases in revenues in both periods were primarily driven by strong sales at ISCOs wholly-owned subsidiary Lifeline Skin Care (LSC). In addition, steady growth in sales from ISCOs other wholly-owned subsidiary, Lifeline Cell Technology (LCT), contributed to the increases in revenues for both periods.

While the Company continued to invest in therapeutic projects, development of new technologies, and expansion of products and channels of distribution, to date we have generated limited revenue to support our core therapeutic research and development efforts. For the three months ended December 31, 2011, development expenses, excluding cost of sales, increased $507,000 or 17% compared with the same period of 2010, a reflection of increased G&A expenses resulting from higher stock-based compensation expenses.

For the twelve months ended December 31, 2011, development expenses, excluding costs of sales, increased approximately $3.0 million or 26% when compared with the prior year period.The majority of the increase was primarily due to increases in general and administrative and research and development activities. General and administrative expenses increased largely due to increased non-cash stock-based compensation, higher headcount, and increased expenses related business development activity and general corporate expenses. Research & Development expenses increased mainly due to increased number and complexity of experiments associated with our scientific projects. The increase in development expenses was also related to increased research activities on therapeutic products and product research activities for LSC and LCT coupled with increased sales and marketing expenses related to our skin care products.

Some of the 2011 Highlights:

-- A number of donors willing to provide oocytes for research purposed were enrolled in ISCO's program to establish a bank of clinical grade hpSC capable of being immune-matched to millions of patients.

-- The Research and Development team successfully completed the first series of preclinical studies that supports the therapeutic use of hepatocytes (liver cells) and neuronal cells derived from human parthenogenetic stem cells (hpSC). These in vivo experiments demonstrated that the derived cells are able to survive in targeted locations in mice without causing tumors.

-- We became Sarbanes-Oxley compliant and maintained, in all material respects, effective internal controls over financial reporting as of December 31, 2011.

-- We strengthened our Management Team through the appointments of well-known industry executives: Kurt May as President & Chief Operating Officer, Linh Nguyen as Chief Financial Officer, Donna Queen as Vice President of Marketing and Business Development for LSC.

See the original post:
International Stem Cell Corporation Announces 2011 Financial Results

-- Allure Image Enhancement Among First to Offer the Stem Cell Facelift and PRP Therapy in the Inland Empire --

UPLAND, CA (PRWEB) March 19, 2012

Stem Cell Facelift with PRP Therapy provides an amazing full facial restoration and can simulate the effects of a face lift, brow lift, and total facial rejuvenation in one sitting. In addition, the benefits of the PRP Therapy with growth factors enhance stem cell survival, giving long lasting and potentially permanent results, says John Grasso MD, Medical Director at Allure Image Enhancement. I find these procedures to be an exciting new approach to the world of dermal fillers. Rather than using lab derived products, patients can enjoy the benefits of volume and longevity from their own cells.

Stem Cells often thought of as controversial and futuristic, are the latest beauty secret now available. Although injectable wrinkle treatments are very popular, there are many who shy away from putting anything foreign into their face. The two most common requests my patients ask me when it comes to anti-aging rejuvenation are: 1. Is there something natural I can use? and 2. Is there anything that lasts longer? Autologous fat transfer enhanced with stem cells and platelet rich plasma is going to change the world of Anti-Aging skin care, says Mina Grasso NP, owner of Allure Image Enhancement. For those who do not have adequate fat deposits or choose not to have autologous fat transfer can still benefit from the healing and repair response of various growth factors and cytokines with PRP alone or combined with manufactured fillers.

Fat transfer has been around for many years and may yield inconsistent results: 50% of the transferred fat usually breaks down within 2 years. Fat is an abundant source of mesenchymal stem cells. The difficulty is that in obtaining fat using Liposuction, up to half of the natural stem cells may be damaged. By adding additional autologous stem cells to the suctioned fat, it closer approximates the original concentration of stem cells in fat in the body and may aid the transplanted fat cells in surviving longer. Platelet Rich Plasma (PRP), which contains growth factors and cytokines, stimulates a repair response in soft tissue when added to the stem cell enhanced fat cells. The grafted fat and stem cells as well as surrounding local cells are activated by these growth factors to generate new growth that plumps up sagging areas. The growth factors enhance the quality of skin on the surface and repair sun damage and skin color irregularities.

Using this revolutionary new method, stem cells show promise in regenerating collagenproducing fibroblasts, cartilage, muscle and even bone cells. Research trials are under way using stem cells to repair other damaged tissue such as lungs, knees, and hearts and reverse neurological degenerative diseases. Stem Cell Facelift with PRP results in long-lasting volume in the treated area, and patients can start to see improvement in skin texture a healthy glow as soon as three weeks following treatment, with dramatic results occurring over a period of two to four months and lasting for years..

About Allure Image Enhancement, Inc.

Founded by Mina Grasso, RN, MSN, FNP-C, and her husband John Grasso MD. Allure Image Enhancement, Inc., for 15 years has served the Inland Empire with the latest in medical esthetics, providing services such as Botox Cosmetic, Restylane, Dysport, Juvderm, Latisse, Laser Hair Removal, Tattoo Removal, Laser Skin Rejuvenation, Vein Treatment, Body Shaping, and many more services.

Contact:

Nicholas Rodgers, CAC

Go here to see the original:
Breakthrough Beauty Procedure Using Your Own Stem Cells Offered in the Inland Empire

Among the primary causes of adult-onset blindness are degenerative diseases of the retina, such as macular degeneration and retinitis pigmentosa. While some treatments have been developed that slow down the rate of degeneration, the clinical situation is still generally unsatisfactory. But if you could grow a new retina, transplant might be a possible cure. Now new hope is springing up from a research project at the University of Wisconsin-Madison in which scientists have succeeded in growing human retinal tissue from stem cells.

Pluripotent stem cells are capable of forming nearly any tissue in the body including retinal tissue. There has been great controversy about using pluripotent stem cells for human research or treatment, as historically the only source was to harvest them from early stage human embryos. Instead, for this work the researchers were able to regress mature body cells back into the pluripotent stem cells from which they originally grew. The process is called reprogramming, and is accomplished by inserting a set of proteins into the cell.

To produce the pluripotent stem cells, a white blood cell was taken from a simple blood sample. Genes which code for the reprogramming proteins are inserted into a plasmid, a nonliving ring of DNA. The cell is then infected with the plasmid, rather as a virus infects a cell, with the difference that the plasmid's genes do not become part of the cell's genetic structure. As the reprogramming proteins are formed within the cell by the plasmid DNA, the cell has a good chance of being reprogrammed into a pluripotent stem cell. This stem cell can then be encouraged to grow and differentiate into retinal tissue rather than make more blood cells.

Laboratory-grown human retinal tissue will certainly be used in testing drugs and to study degenerative diseases of the retina, and may eventually make available a new transplantable retina, or a new retina that is grown in place within the eye.

The figure above compares a schematic of the human retina with a photomicrograph of laboratory-grown retinal tissue. The new tissue has separated into at least three layers of cells, with rudimentary photosensitive rods or cones (red) at the top of the picture, and nerve ganglia (blue-green) at the bottom. The blue cells in the middle layer are likely bipolar retinal cells. The structure of the lab-grown retinal tissue is similar to that of a normal human eye, as can be seen by comparison with the retina schematic. The cells also formed synapses, which provide the channels through which optical information flows to the brain.

"We don't know how far this technology will take us, but the fact that we are able to grow a rudimentary retina structure from a patient's blood cells is encouraging, not only because it confirms our earlier work using human skin cells, but also because blood as a starting source is convenient to obtain," says Dr. David Gamm, pediatric ophthalmologist and senior author of the study. "This is a solid step forward." Further steps are eagerly awaited by those living in the dark.

Source: University of Wisconsin School of Medicine and Public Health

Read more:
Physicians grow retinas from human blood-derived stem cells

29-02-2012 15:30 Scientists have created cerebral cortex cells-- those that make up the brain's gray matter-- from a small sample of skin. Source: Cambridge Read more: http://www.laboratoryequipment.com

Read more:
Brain Cells can be Made from Skin Cells - Video

02-03-2012 11:56 more GOOD NEWS like this here: goo.gl Techniques like this, using our OWN STEM CELLS, not someone else's, are the answer to ALL medical problems including DENTAL. Yes you can even seed new teeth from your own DNA... Tell everyone you know to create the demand for the most personalized medicine possible, ie those using your OWN DNA !!!

Read the rest here:
TITE INVERSION© -The Skin Gun - Video

By Yoon Min-sik The Korea Herald/Asia News Network Thursday, Mar 15, 2012

US scientists have succeeded in making early retina structures by using stem cells from blood, marking a breakthrough toward treating eye diseases, Science Daily reported Tuesday.

The new findings can help study degenerative retinal disorder such as retinitis pigmentosa, a prominent cause of blindness in children and young adults, according to a statement by the University of Wisconsin- Madison research team.

Last year, the group led by Doctor David Gamm was able to create the most primitive structure of a retina with photoreceptors by using embryonic stem cells and stem cells from human skin.

But the structures lacked the organization of a more mature retina.

This time, Gamm's team used induced pluripotent stem cells (iPS) derived from blood gathered from donors.

Induced pluripotent stem cell refer to a cell which can develop into any fetal or adult cell type but is free from ethnic debate because it does not require human ovum to produce.

Scientists extracted a type of blood cell called a T-lymphocyte, which is related to immunity, and reprogrammed the cells into iPS cells. Then they grew retina-like tissues from the iPS cells.

About 16 per cent of the initial retinal structures developed distinct layers, which is a significant advance, as retina forms layer in normal human development.

The arrangement of layers was similar to what is found in the back of the eye.

Read this article:
Scientists produce retina structure from blood-derived cells

ScienceDaily (Mar. 14, 2012) A research team has identified epigenetic signatures, markers on DNA that control transient changes in gene expression, within reprogrammed skin cells. These signatures can predict the expression of a wound-healing protein in reprogrammed skin cells or induced pluripotent stem cells (iPSCs), cells that take on embryonic stem cell properties. Understanding how the expression of the protein is controlled brings us one step closer to developing personalized tissue regeneration strategies using stem cells from a patient, instead of using human embryonic stem cells.

The study was published in the Journal of Cell Science.

When skin cells are reprogrammed, many of their cellular properties are recalibrated as they aquire stem cell properties and then are induced to become skin cells again. In order for these "induced" stem cells to be viable in treatment for humans (tissue regeneration, personalized wound healing therapies, etc.), researchers need to understand how they retain or even improve their characteristics after they are reprogrammed.

Since the initial discovery of reprogramming, scientists have struggled with the unpredictability of the cells due to the many changes that occur during the reprogramming process. Classifying specific epigenetic signatures, as this study did, allows researchers to anticipate ways to produce cell types with optimal properties for tissue repair while minimizing unintended cellular abnormalities.

The researchers used reprogrammed cells to generate three-dimensional connective tissue that mimics an in vivo wound repair environment. To verify the role of the protein (PDGFRbeta) in tissue regeneration and maintenance, the team blocked its cellular expression, which impaired the cells' ability to build tissue.

"We determined that successful tissue generation is associated with the expression of PDGFRbeta. Theoretically, by identifying the epigenetic signatures that indicate its expression, we can determine the reprogrammed cells' potential for maintaining normal cellular characteristics throughout development," said first author Kyle Hewitt, PhD, a graduate of the cell, molecular & developmental biology program at the Sackler School of Graduate Biomedical Sciences, and postdoctoral associate in the Garlick laboratory at Tufts University School of Dental Medicine (TUSDM).

"The ability to generate patient-specific cells from the reprogrammed skin cells may allow for improved, individualized, cell-based therapies for wound healing. Potentially, these reprogrammed cells could be used as a tool for drug development, modeling of disease, and transplantation medicine without the ethical issues associated with embryonic stem cells," said senior author Jonathan Garlick, DDS, PhD, a professor in the department of oral and maxillofacial pathology and director of the division of tissue engineering and cancer biology at TUSDM.

Jonathan Garlick is also a member of the cell, molecular & developmental biology program faculty at the Sackler School and the director of the Center for Integrated Tissue Engineering (CITE) at TUSDM.

Additional authors of the study are Yulia Shamis, MSc, a PhD candidate in the cell, molecular, and developmental biology program at the Sackler School; Elana Knight, BSc, and Avi Smith, BA, both research technicians in the Garlick laboratory; Anna Maione, a PhD student in the cell, molecular & developmental biology program at the Sackler School, and Addy Alt-Holland, PhD, MSc, assistant professor at TUSDM.

This work was supported by grant # DE017413 to Dr. Garlick from the National Institute for Dental and Craniofacial Research, part of the National Institutes of Health.

Original post:
Epigenetic signatures direct the repair potential of reprogrammed cells

Newswise MADISON For the first time, scientists at the University of Wisconsin-Madison have made early retina structures containing proliferating neuroretinal progenitor cells using induced pluripotent stem (iPS) cells derived from human blood.

And in another advance, the retina structures showed the capacity to form layers of cells as the retina does in normal human development and these cells possessed the machinery that could allow them to communicate information. (Light-sensitive photoreceptor cells in the retina along the back wall of the eye produce impulses that are ultimately transmitted through the optic nerve and then to the brain, allowing you to see.) Put together, these findings suggest that it is possible to assemble human retinal cells into more complex retinal tissues, all starting from a routine patient blood sample.

Many applications of laboratory-built human retinal tissues can be envisioned, including using them to test drugs and study degenerative diseases of the retina such as retinitis pigmentosa, a prominent cause of blindness in children and young adults. One day, it may also be possible replace multiple layers of the retina in order to help patients with more widespread retinal damage.

We dont know how far this technology will take us, but the fact that we are able to grow a rudimentary retina structure from a patients blood cells is encouraging, not only because it confirms our earlier work using human skin cells, but also because blood as a starting source is convenient to obtain, says Dr. David Gamm, pediatric ophthalmologist and senior author of the study. This is a solid step forward.

In 2011, the Gamm lab at the UW Waisman Center created structures from the most primitive stage of retinal development using embryonic stem cells and stem cells derived from human skin. While those structures generated the major types of retinal cells, including photoreceptors, they lacked the organization found in more mature retina.

This time, the team, led by Gamm, Assistant Professor of Ophthalmology and Visual Sciences in the UW School of Medicine and Public Health, and postdoctoral researcher and lead author Dr. Joseph Phillips, used their method to grow retina-like tissue from iPS cells derived from human blood gathered via standard blood draw techniques.

In their study, about 16 percent of the initial retinal structures developed distinct layers. The outermost layer primarily contained photoreceptors, whereas the middle and inner layers harbored intermediary retinal neurons and ganglion cells, respectively. This particular arrangement of cells is reminiscent of what is found in the back of the eye. Further, work by Dr. Phillips showed that these retinal cells were capable of making synapses, a prerequisite for them to communicate with one another.

The iPS cells used in the study were generated through collaboration with Cellular Dynamics International (CDI) of Madison, Wis., who pioneered the technique to convert blood cells into iPS cells. CDI scientists extracted a type of blood cell called a T-lymphocyte from the donor sample, and reprogrammed the cells into iPS cells. CDI was founded by UW stem cell pioneer Dr. James Thomson.

We were fortunate that CDI shared an interest in our work. Combining our labs expertise with that of CDI was critical to the success of this study, added Dr. Gamm.

Other members of the research team include:

Excerpt from:
Scientists Produce Eye Structures from Human Blood-Derived Stem Cells

CARLSBAD, Calif.--(BUSINESS WIRE)--

International Stem Cell Corporation (OTCBB:ISCO.OB - News) http://www.internationalstemcell.com, a California-based biotechnology company focused on therapeutic, cosmetic and research products, announced today that it had obtained new capital financing and made important changes in the composition of its Board of Directors to ensure that Independent Directors hold the majority of Board seats.

The financing consists of $5 million in newly issued Series G Convertible Preferred Stock (without warrants), convertible into Common Stock at a conversion price of $0.40/share, the market price of the Companys Common Stock on the date the offer to purchase was made. This financing was made by AR Partners LLC, a healthcare investment firm owned by Dr. Andrey Semechkin, ISCOs CEO and Co-Chairman of the Board of Directors.

Concurrently with the closing of this financing, the Company elected to its Board of Directors Dr. James Berglund, co-founder of Enterprise Partners Venture Capital - one of the premier venture capital firms in the field of healthcare technology founded in 1985. Dr. Berglund, with his extensive professional experience, continues as an active participant in the biotech and healthcare industries. Dr. Berglund will replace Kenneth C. Aldrich, co-founder and former CEO of the Company during the period 2008-2009, who is stepping down as ISCO Board of Directors Co-Chairman. Although Mr. Aldrich is retiring from our Board, he will remain as one of ISCOs largest shareholders and an active consultant to the Board and executive management and will continue to represent the Company as Chairman Emeritus in a variety of public and private venues.

According to Mr. Aldrich, In my view, Dr. Semechkins willingness to commit such a significant amount of capital to ISCO at the market price of the Companys stock on the date of his offer represents a major vote of confidence in ISCOs future by its most senior executive. We are thankful to Dr. Semechkin for his support that will further advance ISCOs parthenogenetic stem cell-based therapeutic programs and income generating businesses.

Having a majority of independent directors on our companys Board represents an important step in ISCOs development and in transforming ISCO into a leading public company in the field of regenerative medicine.

I want to thank Mr. Aldrich for his long-standing dedication and continued involvement in guiding the Company, said Dr. Semechkin. This long-term investment, along with the new executive management team recruited over the previous twelve months, will provide ISCO with the necessary economic stability and resources to pursue its goals of consolidating our leadership position and accelerating our therapeutic programs, continued Dr. Semechkin.

About International Stem Cell Corporation

International Stem Cell Corporation is focused on the therapeutic applications of human parthenogenetic stem cells and the development and commercialization of cell-based research and cosmetic products. ISCO's core technology, parthenogenesis, results in the creation of pluripotent human stem cells from unfertilized oocytes (eggs). HpSCs avoid ethical issues associated with the use or destruction of viable human embryos. ISCO scientists have created the first parthenogenic, homozygous stem cell line that can be a source of therapeutic cells with minimal immune rejection after transplantation into hundreds of millions of individuals of differing genders, ages and racial backgrounds. This offers the potential to create the first true stem cell bank, UniStemCell. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology, and cell-based skin care products through its subsidiary Lifeline Skin Care. More information is available at http://www.internationalstemcell.com.

To subscribe to receive ongoing corporate communications, please click on the following link: http://www.b2i.us/irpass.asp?BzID=1468&to=ea&s=0.

Read the original post:
International Stem Cell Corporation Completes $5 Million Financing and Elects Jim Berglund to the Board of Directors

24-02-2012 07:37 This is a beautiful image of human brain cells, which can now be grown from adult skin cells. Under the Microscope is a collection of videos that show glimpses of the natural and man-made world in stunning close-up. They are released every Monday and Thursday and you can see them here: bit.ly Yichen Shi: "Brain neural stem cells derived from human skin cells: these stem cells express typical marker genes of brain neocortical stem cells, such as Pax6 (Red fluorescent labeled), and form a rosette structure resembling the transection of the neural tube." The entire image is about 250 ?m across (a really thick bit of human hair). More info: http://www.cam.ac.uk en.wikipedia.org Picture taken by Yichen Shi in the Livesey Lab http://www.gurdon.cam.ac.uk Voice over by Fred Lewsey. Music by Peter Nickalls: http://www.peternickalls.com

Excerpt from:
Under the Microscope #12 - Video

CARLSBAD, Calif.--(BUSINESS WIRE)--

International Stem Cell Corporation (OTCBB:ISCO.OB - News) today announced that Co-Chairman Kenneth Aldrich and President and Chief Operating Officer Kurt May will be presenting at the 24th Annual Roth Conference on Wednesday, March 14, 2012 at 1:00 p.m. Pacific time. The conference is being held March 11-14 at the Ritz Carlton Hotel in Dana Point, California.

About International Stem Cell Corporation

International Stem Cell Corporation is focused on the therapeutic applications of human parthenogenetic stem cells (hpSCs) and the development and commercialization of cell-based research and cosmetic products. ISCO's core technology, parthenogenesis, results in the creation of pluripotent human stem cells from unfertilized oocytes (eggs). hpSCs avoid ethical issues associated with the use or destruction of viable human embryos. ISCO scientists have created the first parthenogenic, homozygous stem cell line that can be a source of therapeutic cells for hundreds of millions of individuals of differing genders, ages and racial background with minimal immune rejection after transplantation. hpSCs offer the potential to create the first true stem cell bank, UniStemCell. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology, and cell-based skin care products through its subsidiary Lifeline Skin Care. More information is available at http://www.internationalstemcell.com.

To subscribe to receive ongoing corporate communications, please click on the following link: http://www.b2i.us/irpass.asp?BzID=1468&to=ea&s=0.

Read more:
International Stem Cell Corporation to Present at the Roth Conference on March 14

alan bernstein From Wednesday's Globe and Mail Published Wednesday, Mar. 07, 2012 2:00AM EST

Most Canadians are unaware that two of their own a lanky physics whiz from Alberta and a rumpled Shakespeare-quoting MD from Toronto made a discovery 50 years ago that transformed the understanding of human biology and opened new doors to the treatment of cancer and other diseases.

Toiling away in labs atop Torontos old Princess Margaret Hospital, James Edgar Till and Ernest Armstrong (Bun) McCulloch proved that a single rare cell could produce the red blood cells, white blood cells and platelets needed to make blood, while simultaneously reproducing itself. Dr. Till and Dr. McCulloch originally called the cell a colony-forming unit. Today, its better known as a stem cell.

A great new book, Dreams and Due Diligence, by Joe Sornberger, tells the story. Still, that so few of us know let alone celebrate the fact that the stem cell is a Canadian discovery is baffling. Canada founded the entire field of stem-cell science. We have done much of the heavy lifting for decades: discovering neural stem cells, skin stem cells and cancer stem cells. If hockey is Canadas game, stem-cell science is Canadas science. Not knowing about Dr. Till and Dr. McCulloch is not knowing about Maurice Richard and Wayne Gretzky.

The way it happened didnt help. Their original paper was published in an obscure journal, Radiation Research, in 1961. Public interest went viral only after American James Thomson isolated human embryonic stem cells in 1998, which simultaneously raised hopes that stem cells could be used to repair any damaged cell in the body and ethical concerns that doing so would encourage the destruction of human embryos.

In 2002, the Canadian Institutes of Health Research developed guidelines for all stem-cell research carried out in Canada with its funds. These guidelines have become the gold standard for other countries, including the United States.

Whats even more remarkable is that Canada does such groundbreaking research on a dime. The all in investment in stem-cell research in Canada public, private and charitable funding is about $75-million. This support is provided by Canadians through taxes, donations to health charities and the generosity of community leaders individuals such as Robert and Cheryl McEwen of Toronto and the late Harley Hotchkiss of Calgary. But we still seriously lag behind California, which, with roughly the same population as Canada, has committed $3-billion over 10 years for stem-cell research.

How much further Canadas star scientists can go, however, is in doubt. According to the Stem Cell Network, there are 40 to 50 early-phase clinical trials using transplanted cells ready to roll out over the next four years. All are currently unfunded.

Prime Minister Stephen Harper has said his government will continue to make the key investments in science and technology but bemoaned Canadas less-than-optimal results for those investments. Stem-cell research has already proved itself a sound investment: Dr. Till and Dr. McCullochs work formed the basis of the bone marrow transplantation program at Princess Margaret Hospital that alone has saved thousands of lives. But it will take more than government funding: Private industry and private citizens also need to support life-saving research.

Canadians have good reason to be proud of our countrys contributions to health research and medicine. Two stand out as landmarks: the discovery of insulin in the 1920s and the discovery of stem cells in the 1960s. On Wednesday, at a dinner that brings together many of the countrys leading figures in business, the arts, entertainment, sports and science, the Canadian Stem Cell Foundation will be launched. The event will look back at that great discovery 50 years ago and look forward to ensure that Canadians continue to contribute to stem-cell research and its application to human disease.

The rest is here:
If Canada's game is hockey, its science is stem cells

19-02-2012 22:16 SNP Stem Cell Activator Program : Functional wrinkle cosmetic product Registered for the first time in the nation and third in the world in ICID and contains a new natural material called stem cell activator. SNP ACSYS LINE : SNP ACSYS LINE is the foundation exclusive for oily and troubled skin. It makes oily and troubled skin texture, which is shiny and sticky, neat and clean by adjusting excessively secreted serum. snpcos.en.ecplaza.net

See the rest here:
Stem Cell Activator Program by SD Biotechnologies - Video

Public release date: 1-Mar-2012 [ | E-mail | Share ]

Contact: Nicole Giese Rura rura@wi.mit.edu 617-258-6851 Whitehead Institute for Biomedical Research

FINDINGS: Devising a novel method to identify potential genetic regulators in planarian stem cells, Whitehead Institute scientists have determined which of those genes affect the two main functions of stem cells. Three of the genes are particularly intriguing because they code for proteins similar to those known to regulate mammalian embryonic stem cells. Such genetic similarity makes planarians an even more attractive model for studying stem cell biology in vivo.

RELEVANCE: Stem cells may hold the promise to regrow damaged, diseased, or missing tissues in humans, such as insulin-producing cells for diabetics and nerve cells for patients with spinal cord injuries. With its renowned powers of regeneration and more than half of its genes having human homologs, the planarian seems like a logical choice for studying stem cell behavior. Yet, until now, scientists have been unable to efficiently identify the genes that regulate the planarian stem cell system.

CAMBRIDGE, Mass. Despite their unassuming appearance, the planarian flatworms in Whitehead Institute Member Peter Reddien's lab are revealing powerful new insights into the biology of stem cellsinsights that may eventually help such cells deliver on a promising role in regenerative medicine.

In this week's issue of the journal Cell Stem Cell, Reddien and scientists in his lab report on their development of a novel approach to identify and study the genes that control stem cell behavior in planarians. Intriguingly, at least one class of these genes has a counterpart in human embryonic stem cells.

"This is a huge step forward in establishing planarians as an in vivo system for which the roles of stem cell regulators can be dissected," says Reddien, who is also an associate professor of biology at MIT and a Howard Hughes Medical Institute (HHMI) Early Career Scientist. "In the grand scheme of things for understanding stem cell biology, I think this is a beginning foray into seeking general principles that all animals utilize. I'd say we're at the beginning of that process."

Planarians (Schmidtea mediterranea) are tiny freshwater flatworms with the ability to reproduce through fission. After literally tearing themselves in half, the worms use stem cells, called cNeoblasts, to regrow any missing tissues and organs, ultimately forming two complete planarians in about a week.

Unlike muscle, nerve, or skin cells that are fully differentiated, certain stem cells, such as cNeoblasts and embryonic stem cells are pluripotent, having the ability to become almost cell type in the body. Researchers have long been interested in harnessing this capability to regrow damaged, diseased, or missing tissues in humans, such as insulin-producing cells for diabetics or nerve cells for patients with spinal cord injuries.

Several problems currently confound the therapeutic use of stem cells, including getting the stem cells to differentiate into the desired cell type in the appropriate location and having such cells successfully integrate with surrounding tissues, all without forming tumors. To solve these issues, researchers need a better understanding of how stem cells tick at the molecular level, particularly within the environment of a living organism. To date, a considerable amount of embryonic stem cell research has been conducted in the highly artificial environment of the Petri dish.

Read this article:
Planarian genes that control stem cell biology identified

Scientists are growing living brain cells from skin samples which could help research into treatments for schizophrenia and bipolar disorder.

Scientists at the University of Edinburgh are growing the cells from skin samples taken from families known to carry faulty genes, which are believed to cause mental illness.

The project, which has received 1 million in funding from the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), aims to develop brain stem cells that could be used to test and screen drugs.

Scientists said it is not easy to understand the diseases using animal models and it is difficult to predict if possible new treatments will work.

They hope using cell-based systems derived from the skin or hair of affected patients will enable researchers to create tests that are more relevant to the disease in humans, and will reduce the dependence on animal models.

Andrew McIntosh, professor of biological psychiatry, said: "We are making different types of brain cells out of skin samples from people with bipolar disorder and schizophrenia.

"Once we have grown these in the laboratory we can then study the cells' neurological function and see how they respond to standard psychiatric treatments. Following this, we hope to be able to screen new medicines."

In the past, researchers used brain tissue from people with schizophrenia and bipolar depression from deceased donors to gain insight into these brain conditions. Scientists said that access to the living brain cells is an exciting development in studying mental illness.

The university said that between 1% and 4% of the world's population is diagnosed with bipolar disorder or schizophrenia, for which there are few highly effective treatments. Little is known about the causes of these conditions but a genetic component is involved as it can run in families.

Well over a million people in the UK are said to be affected by these conditions.

Link:
Living brain cells used in research

For 60 years, doctors have believed women were born with all the eggs they'll ever have. Now Harvard scientists are challenging that dogma, saying they've discovered the ovaries of young women harbor very rare stem cells capable of producing new eggs.

If Sunday's report is confirmed, harnessing those stem cells might one day lead to better treatments for women left infertile because of disease or simply because they're getting older.

"Our current views of ovarian aging are incomplete. There's much more to the story than simply the trickling away of a fixed pool of eggs," said lead researcher Jonathan Tilly of Harvard's Massachusetts General Hospital, who has long hunted these cells in a series of controversial studies.

Tilly's previous work drew fierce skepticism, and independent experts urged caution about the latest findings.

A key next step is to see whether other laboratories can verify the work. If so, then it would take years of additional research to learn how to use the cells, said Teresa Woodruff, fertility preservation chief at Northwestern University's Feinberg School of Medicine.

Still, even a leading critic said such research may help dispel some of the enduring mystery surrounding how human eggs are born and mature.

"This is going to spark renewed interest, and more than anything else it's giving us some new directions to work in," said David Albertini, director of the University of Kansas' Center for Reproductive Sciences. While he has plenty of questions about the latest work, "I'm less skeptical," he said.

Scientists have long taught that all female mammals are born with a finite supply of egg cells, called ooctyes, that runs out in middle age. Tilly, Mass General's reproductive biology director, first challenged that notion in 2004, reporting that the ovaries of adult mice harbor some egg-producing stem cells. Recently, Tilly noted, a lab in China and another in the U.S. also have reported finding those rare cells in mice.

But do they exist in women? Enter the new work, reported Sunday in the journal Nature Medicine.

First Tilly had to find healthy human ovaries to study. He collaborated with scientists at Japan's Saitama Medical University, who were freezing ovaries donated for research by healthy 20-somethings who underwent a sex-change operation.

Continued here:
Women Have Egg-Producing Stem Cells

These human eggs (oocytes) can now be made from adult ovaries; Credit: Shutterstock

Yvonne A R White, Dori C Woods, Yasushi Takai, Hiroyuki Seki and Jonathan L Tilly worked hard in 2004. When this intrepid team revealed that some mammals (eg. mice) can produce eggs into their adult life, there was hope that stem cells could now become a staple of medical ideas. That hope has been fully justified. Published in the March issue of Nature Medicine, the same team have explored human female ovary capabilities and performed what was thought the impossible.

We may all know that female babies are born with their full and finite complement of oocytes or eggs, but we are only partly correct. Now the possibilities have enlarged. The proof that you could find egg-producing stem cells in the ovary of adult women was paramount for this team of scientists.

Dr. Jonathan Tilly directs the Vincent Center in Massachusetts General Hospital: "The discovery of oocyte precursor cells in adult human ovaries, coupled with the fact that these cells share the same characteristic features of their mouse counterparts that produce fully functional eggs, opens the door for development of unprecedented technologies to overcome infertility in women and perhaps even delay the timing of ovarian failure." Presumably, stem cell researchers will read much more into this.

Shanghai mouse research provided support with proof of egg-producing stem cells in 2009 and then the Vincent team developed a more precise green fluorescence-activated cell-sorting technique(GFP), whereby no possibility of contamination from other cells was possible. The verified eggs they produced could then be fertilised and developed into blastocysts. Now for human tissues. The resultant oocytes (eggs) not only looked like and grew like those in human ovaries, but some had the required haploid number of chromosomes, presumably after meiosis (all true eggs of course have to double up their DNA later, when fertilised.)

This cross-section of a human ovary shows potential areas for stem cells -which can now be converted to oocytes - even in adult women; Credit: Shutterstock

The final step, to date, involved using mouse recipients for the human tissue. Immature human follicles and oocytes were found after 7-14 days, and possibly were present before the mouse skin graft. Dr. Tilly and the team are now exploring the freezing of these cells in human OSC banks, as human eggs cannot be frozen and thawed without damage.

Likewise, factors such as hormones that influence the marvellous transformation from OSC to oocyte need to be identified with IVF and other infertility possibilities become let us say, "improved" spectacularly by these discoveries. Women's health generally could also be improved by maintaining some functions in the ovary throughout life. Let us be clear that with even more from these particular stem cells, a fascinating transformation of the whole of medicine lies ahead.

Read the original:
Eggs from Stem Cells excite the imagination

16-02-2012 10:34 http://www.ova-skin.com http Linda Barnes, national sales director for Dr. Lam's new skin care line Ova, offers her greetings as part of the extended staff at Lam Facial Plastics key words: skin care, ova, plant stem cells, plano, dallas, texas, plastic surgery, linda barnes, dr. sam lam

Read this article:
Linda, Sales Director for Ova Skin Care - Video

These human eggs (oocytes) can now be made from adult ovaries; Credit: Shutterstock

Yvonne A R White, Dori C Woods, Yasushi Takai, Hiroyuki Seki and Jonathan L Tilly worked hard in 2004. When this intrepid team revealed that some mammals (eg. mice) can produce eggs into their adult life, there was hope that stem cells could now become a staple of medical ideas. That hope has been fully justified. Published in the March issue of Nature Medicine, the same team have explored human female ovary capabilities and performed what was thought the impossible.

We may all know that female babies are born with their full and finite complement of oocytes or eggs, but we are only partly correct. Now the possibilities have enlarged. The proof that you could find egg-producing stem cells in the ovary of adult women was paramount for this team of scientists.

Dr. Jonathan Tilly directs the Vincent Center in Massachusetts General Hospital: "The discovery of oocyte precursor cells in adult human ovaries, coupled with the fact that these cells share the same characteristic features of their mouse counterparts that produce fully functional eggs, opens the door for development of unprecedented technologies to overcome infertility in women and perhaps even delay the timing of ovarian failure." Presumably, stem cell researchers will read much more into this.

Shanghai mouse research provided support with proof of egg-producing stem cells in 2009 and then the Vincent team developed a more precise green fluorescence-activated cell-sorting technique(GFP), whereby no possibility of contamination from other cells was possible. The verified eggs they produced could then be fertilised and developed into blastocysts. Now for human tissues. The resultant oocytes (eggs) not only looked like and grew like those in human ovaries, but some had the required haploid number of chromosomes, presumably after meiosis (all true eggs of course have to double up their DNA later, when fertilised.)

This cross-section of a human ovary shows potential areas for stem cells -which can now be converted to oocytes - even in adult women; Credit: Shutterstock

The final step, to date, involved using mouse recipients for the human tissue. Immature human follicles and oocytes were found after 7-14 days, and possibly were present before the mouse skin graft. Dr. Tilly and the team are now exploring the freezing of these cells in human OSC banks, as human eggs cannot be frozen and thawed without damage.

Likewise, factors such as hormones that influence the marvellous transformation from OSC to oocyte need to be identified with IVF and other infertility possibilities become let us say, "improved" spectacularly by these discoveries. Women's health generally could also be improved by maintaining some functions in the ovary throughout life. Let us be clear that with even more from these particular stem cells, a fascinating transformation of the whole of medicine lies ahead.

See the original post here:
Eggs from Stem Cells excite the imagination

An experiment that has produced human eggs from stem cells could be a boon for women desperate to have a baby, scientists claim.

New research has swept away the belief women only have a limited stock of eggs and replaces it with the theory the supply is continuously replenished from precursor cells in the ovary.

'The prevailing dogma in our field for the better part of the last 50 or 60 years was that young girls at birth were given a bank account of eggs at birth that's not renewable,' says Jonathan Tilly, director of the Vincent Center for Reproductive Biology at Massachusetts General Hospital, who led the research.

'As they become mature and become a woman, they use those eggs up (and) the ovaries will fail when they enter menopause.'

Tilly first challenged the 'bank account' doctrine eight years ago, suggesting female mammals continue producing egg-making cells into adulthood rather than from a stock acquired at birth.

His theory ran into a firestorm.

Other scientists challenged the accuracy of his experiments or dismissed their conclusions as worthless, given they were only conducted on lab mice.

But Tilly says the new work not only confirms his controversial idea, it takes it further.

In it, his team isolated egg-producing stem cells in human ovaries and then coaxed them into developing oocytes, as eggs are called.

Building on a feat by Chinese scientists, they pinpointed the oocyte stem cells by using antibodies which latched onto a protein 'handle' located on the side of these cells.

The team tagged the stem cells with a fluorescent green protein - a common trick to help figure out what happens in lab experiments.

The cells were injected into biopsied human ovarian tissue which was then grafted beneath the skin of mice.

Within 14 days, the graft had produced a budding of oocytes. Some of the eggs glowed with the fluorescent tag, proving that they came from the stem cells. But others did not, which suggested they were already present in the tissue before the injection.

Tilly said 'the hairs were standing up on my arm' when he saw time-elapse video showing the eggs maturing in a lab dish.

Further testing needs to be done but Tilly says the work could be far-reaching.

Go here to read the rest:
Human eggs produced from stem cells

ScienceDaily (Feb. 26, 2012) — For the first time, Massachusetts General Hospital (MGH) researchers have isolated egg-producing stem cells from the ovaries of reproductive age women and shown these cells can produce what appear to be normal egg cells or oocytes. In the March issue of Nature Medicine, the team from the Vincent Center for Reproductive Biology at MGH reports the latest follow-up study to their now-landmark 2004 Nature paper that first suggested female mammals continue producing egg cells into adulthood.

"The primary objective of the current study was to prove that oocyte-producing stem cells do in fact exist in the ovaries of women during reproductive life, which we feel this study demonstrates very clearly," says Jonathan Tilly, PhD, director of the Vincent Center for Reproductive Biology in the MGH Vincent Department of Obstetrics and Gynecology, who led the study. "The discovery of oocyte precursor cells in adult human ovaries, coupled with the fact that these cells share the same characteristic features of their mouse counterparts that produce fully functional eggs, opens the door for development of unprecedented technologies to overcome infertility in women and perhaps even delay the timing of ovarian failure."

The 2004 report from Tilly's team challenged the fundamental belief, held since the 1950s, that female mammals are born with a finite supply of eggs that is depleted throughout life and exhausted at menopause. That paper and a 2005 follow-up published in Cell showing that bone marrow or blood cell transplants could restore oocyte production in adult female mice after fertility-destroying chemotherapy were controversial; but in the intervening years, several studies from the MGH-Vincent group and other researchers around the world have supported Tilly's work and conclusions.

These supporting studies include a 2007 Journal of Clinical Oncology report from the MGH-Vincent team that showed female mice receiving bone marrow transplants after oocyte-destroying chemotherapy were able to have successful pregnancies, delivering pups that were their genetic offspring and not of the marrow donors. A 2009 study from a team at Shanghai Jiao Tong University in China, published in Nature Cell Biology, not only isolated and cultured oocyte-producing stem cells (OSCs) from adult mice but also showed that those OSCs, after transplantation into the ovaries of chemotherapy-treated female mice, gave rise to mature oocytes that were ovulated, fertilized and developed into healthy offspring.

"That study singlehandedly deflated many of the arguments from critics of our earlier Nature paper by showing that oocyte-producing stem cells exist in mice and could develop into fully functional eggs," says Tilly. Another paper from a west-coast biotechnology company, published in Differentiation in 2010, provided further independent confirmation of Tilly's earlier conclusions regarding the presence of oocyte-producing stem cells in ovaries of adult mice.

Tilly is quick to point out, however, "These follow-up studies, while providing definitive evidence that oocyte-producing stem cells exist in ovaries of adult female mammals, were not without their limitations, leaving the question open in some scientific circles of whether the adult oocyte pool can be renewed. For example, the protocol used to isolate OSCs in the 2009 Nature Cell Biology study is a relatively crude approach that often results in the contamination of desired cells by other cell types." To address this, the MGH-Vincent team developed and validated a much more precise cell-sorting technique to isolate OSCs without contamination from other cells.

The 2009 study from China also had isolated OSCs based on cell-surface expression of a marker protein called Ddx4 or Mvh, which previously had been found only in the cytoplasm of oocytes. This apparent contradiction with earlier studies raised concerns over the validity of the protocol. Using their state-of-the-art fluorescence-activated cell sorting techniques, the MGH-Vincent team verified that, while the marker protein Ddx4 was indeed located inside oocytes, it was expressed on the surface of a rare and distinct population of ovarian cells identified by numerous genetic markers and functional tests as OSCs.

To examine the functional capabilities of the cells isolated with their new protocol, the investigators injected green fluorescent protein (GFP)-labeled mouse OSCs into the ovaries of normal adult mice. Several months later, examination of the recipient mouse ovaries revealed follicles containing oocytes with and without the marker protein. GFP-labeled and unlabeled oocytes also were found in cell clusters flushed from the animals' oviducts after induced ovulation. The GFP-labeled mouse eggs retrieved from the oviducts were successfully fertilized in vitro and produced embryos that progressed to the hatching blastocyst stage, a sign of normal developmental potential. Additionally, although the Chinese team had transplanted OSCs into ovaries of mice previously treated with chemotherapy, the MGH-Vincent team showed that it was not necessary to damage the recipient mouse ovaries with toxic drugs before introducing OSCs.

In their last two experiments, which Tilly considers to be the most groundbreaking, the MGH-Vincent team used their new cell-sorting techniques to isolate potential OSCs from adult human ovaries. The cells obtained shared all of the genetic and growth properties of the equivalent cells isolated from adult mouse ovaries, and like mouse OSCs, were able to spontaneously form cells with characteristic features of oocytes. Not only did these oocytes formed in culture dishes have the physical appearance and gene expression patterns of oocytes seen in human ovaries -- as was the case in parallel mouse experiments -- but some of these in-vitro-formed cells had only half of the genetic material normally found in all other cells of the body. That observation indicates that these oocytes had progressed through meiosis, a cell-division process unique to the formation of mature eggs and sperm.

The researchers next injected GFP-labeled human OSCs into biopsied human ovarian tissue that was then grafted beneath the skin of immune-system-deficient mice. Examination of the human tissue grafts 7 to 14 days later revealed immature human follicles with GFP-negative oocytes, probably present in the human tissue before OSC injection and grafting, as well as numerous immature human follicles with GFP-positive oocytes that would have originated from the injected human OSCs.

"These experiments provide pivotal proof-of-concept that human OSCs reintroduced into adult human ovarian tissue performed their expected function of generating new oocytes that become enclosed by host cells to form new follicles," says Tilly, a professor of Obstetrics, Gynecology and Reproductive Biology at Harvard Medical School and chief of Research at the MGH Vincent Department of Obstetrics and Gynecology. "These outcomes are exactly what we see if we perform the same experiments using GFP-expressing mouse OSCs, and GFP-expressing mouse oocytes formed that way go on to develop into fully functional eggs.

"In this paper we provide the three key pieces of evidence requested by those who have been skeptical of our previous work," he adds. "We developed and extensively validated a cell-sorting protocol to reliably purify OSCs from adult mammalian ovaries, proving once again that these very special cells exist. We tested the function of mouse oocytes produced by these OSCs and showed that they can be fertilized to produce healthy embryos. And we identified and characterized an equivalent population of oocyte-producing stem cells isolated from adult human ovaries."

Among the many potential clinical applications for these findings that Tilly's team is currently exploring are the establishment of human OSC banks -- since these cells, unlike human oocytes, can be frozen and thawed without damage -- the identification of hormones and factors that accelerate the formation of oocytes from human OSCs, the development of mature human oocytes from OSCs for in vitro fertilization, and other approaches to improve the outcomes of IVF and other infertility treatments.

Tilly notes that an essential part of his group's accomplishment was collaboration with study co-author Yasushi Takai, MD, PhD, a former MGH research fellow on Tilly's team and now a faculty member at Saitama Medical University in Japan. Working with his clinical colleagues at Saitama, Takai was able to provide healthy ovarian tissue from consenting patients undergoing sex reassignment surgery, many in their 20s and early 30s. Co-lead authors of the Nature Medicine report are Yvonne White, PhD, and Dori Woods, PhD, of the Vincent Center for Reproductive Biology at MGH. Additional co-authors are Osamu Ishihara, MD, PhD, and Hiroyuki Seki, MD, PhD, of Saitama Medical University.

The study was supported by a 10-year MERIT Award to Tilly from the National Institute on Aging, a Ruth L. Kirschstein National Research Service Award from the National Institutes of Health, the Henry and Vivian Rosenberg Philanthropic Fund, the Sea Breeze Foundation, and Vincent Memorial Hospital Research Funds.

Recommend this story on Facebook, Twitter,
and Google +1:

Other bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by Massachusetts General Hospital.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Yvonne A R White, Dori C Woods, Yasushi Takai, Osamu Ishihara, Hiroyuki Seki, Jonathan L Tilly. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nature Medicine, 2012; DOI: 10.1038/nm.2669

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Read this article:
Egg-producing stem cells isolated from adult human ovaries