Archive for the ‘Skin Stem Cells’ Category

7 hours ago These are fossil remains of Ediacara biota. Credit: Marc Laflamme

Bigger really is better at least it was for early prehistoric life. A NASA research group featuring University of Toronto Mississauga professor Marc Laflamme has helped to explain why some prehistoric organisms evolved into larger animals.

Laflamme, an assistant professor with the Department of Chemical and Physical Sciences, and his colleagues at the Massachusetts Institute of Technology Node of NASA's Astrobiology Institute suggest that height offered a distinct advantage to the earliest forms of multicellular life.

Working to further the NASA Astrobiology Institute's research into the origins of life on earth and the possibility of life elsewhere in the universe, the multinational group used a technique known as canopy flow modeling to reconstruct ocean currents operating in the deep seas some 580 million years ago.

The three-dimensional modeling helped to illustrate how dense communities of bacteria and multicellular organisms competed for nutrients in Pre-Cambrian seas.

According to the study, published in the science journal Current Biology, primitive multicellular organisms known as Ediacara biota took on larger sizes in order to access nutrient-rich currents occurring above the seabed.

These enigmatic leaf-shaped life-forms grew up to a metre in height and are thought to be among the earliest assortment of large, multicellular life.

Whether Ediacara represent the earliest animal lineages or an entirely extinct group of multicellular life is still a mystery, and an active research direction for Laflamme.

Laflamme and his colleagues suggest large Ediacara were able to absorb nutrients in higher quantities, which in turn helped to fuel the high energy costs associated with increased size.

The study also suggests that large Ediacara altered the flow of surrounding ocean currents, thus promoting further growth.

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Study shows size matters in prehistoric seas

Renew

Revolutionary skin care with a novel,proprietary approach tocellular aging.

The bodys signals govern skin stem cells, controlling the decision to remain dormant, divide or differentiate (become normal, active tissue cells). Signals flow in path-ways and multiple paths funnel into the common Wnt signaling pathway. Signaling stimulatesskin stem cells to begin the process leading to fibroblasts, keratino-

cytesand other dermal/epidermalcells.

Renewnt skin care products contain the high-end ingredients available today for cosmeceuticals, but also have an entirely new technology,Asymmtate.Unlike many cosmetic agents, Asymmtate has been clinically provento penetrate through the epidermis into the dermis. Makucell currentlyoffers fourtargeted skin careproducts.

Asymmtate AwakensSkin's Stem Cells

Asymmtateis a small molecule that optimizes signaling in the Wnt Pathway and was developed by a team of researchers led byDr. Michael Kahn of the Eli and Edythe Broad Center for Regenerative Medicine at the Keck School of Medicine of the University of Southern California.

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Makucell - Best Anti Aging Skin Care

STEMCORE-3 SETS STEMOLOGY APART AS FIRST AND ONLY SKINCARE LINE TO COMBINE HUMAN ADULT AND PLANT STEM CELLS - http://www.stemologyskincare.com. (PRNewsFoto/DermaTech Research Laboratories)

LOS ANGELES, Jan. 22, 2014 /PRNewswire-iReach/ -- DermaTech Research Laboratories reveals StemCore-3TM, a proprietary technology that provides the most powerful combination of skin and collagen growth boosters available in any anti-aging skin care product today, as the key to Stemology, the world's first and only skincare line to incorporate the superior features of both humanadultstem cellsand plant stem cells. This exclusive formulation provides superior anti-aging efficacy that is ethically prepared, contains no DNA or stem cell matter, and is all natural and intelligently organic whenever possible.

(Photo: http://photos.prnewswire.com/prnh/20140122/MN48823)

The StemCore-3 complex helps to stimulate the natural process of tissues by providing additional natural growth factors and other molecules normally found in young, healthy tissue and skin, while supplying protein nutrients needed for cellular development.Scientific studies have shown that it stimulates the skin's growth factor communication between the epidermal and the dermal layers, thus causing an increase in collagen production in aging skin. This is natural appearance rejuvenation in its truest sense - a body systems approach.

"It is our StemCore-3 complex that allows us to promise superior anti-aging efficacy. Stemology products containing StemCore-3 have been clinically proven to significantly improve all 12 signs of facial aging including fine lines and wrinkles, skin elasticity, firmness, brightness, skin tone, pore refinement, skin thickness, collagen and free radical damage," says Hal Simeroth, Ph.D., Co-Founder and CTO of DermaTech Research, and lead formulator for Stemology. "With over 10 years experience in the biotechnology field, the creation of StemCore-3 and the resulting Stemology brand is my greatest achievement."

The three components in the StemCore-3 complex are:

Each component of the complex makes its own unique contribution in providing a recharging effect for skin stem cells, collagen fibroblasts and the ECM, TA cells, and keratinocytes similar to that which naturally occurred in youth. This "best of" approach maximizes Stemology's ability to help prevent and improve the number one cause of skin aging - the declining production of epidermal, collagen and elastin cells, which results in dull, thin and wrinkled skin.

StemCore-3 is a proprietary stem cell-based peptide that is contained in all Stemology treatment products and is not available in any other product on the market.

Stemology is committed to the ethical collection and use of stem cells, and only uses adult human stem cell technology gathered from certified, volunteer human bone marrow donors. Stemology never uses human or animal embryonic stem cells, and no human or animal is harmed during stem cell harvesting. Stemology products are all natural, and intelligently organic wherever possible and free of phthalates, parabens, GMO's and petrochemicals.

Stemology is an all natural, intelligently organic wherever possible, anti-aging skincare line that combines the very best of science and nature to address the most prevalent skin and aging concerns. Utilizing proprietary stem cell technologies, Stemology products help rescue, refresh, renew, revive, and reboot aging skin.

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StemCore-3 Sets Stemology Apart As First And Only Skincare ...

Jan. 19, 2014 Normally, tissue injury triggers a mechanism in cells that tries to repair damaged tissue and restore the skin to a normal, or homeostatic state. Errors in this process can give rise to various problems, such as chronic inflammation, which is a known cause of certain cancers.

"It has been noted that cancer resembles a state of chronic wound healing, in which the wound-healing program is erroneously activated and perpetuated," says Professor Adrian Krainer of Cold Spring Harbor Laboratory (CSHL). In a paper published today in Nature Structural & Molecular Biology, a team led by Dr. Krainer reports that a protein they show is normally involved in healing wounds and maintaining homeostasis in skin tissue is also, under certain conditions, a promoter of invasive and metastatic skin cancers.

The protein, called SRSF6, is what biologists call a splicing factor: it is one of many proteins involved in an essential cellular process called splicing. In splicing, an RNA "message" copied from a gene is edited so that it includes only the portions needed to instruct the cell how to produce a specific protein. The messages of most genes can be edited in multiple ways, using different splicing factors; thus, a single gene can give rise to multiple proteins, with distinct functions.

The SRSF6 protein, while normally contributing to wound healing in skin tissue, when overproduced can promote abnormal growth of skin cells and cancer, Krainer's team demonstrated in experiments in mice. Indeed, they determined the spot on a particular RNA message -- one that encodes the protein tenascin C -- where SRSF6 binds abnormally, giving rise to alternate versions of the tenascin C protein that are seen in invasive and metastatic cancers.

The CSHL team also found that overproduction of SRSF6 in mice results in the depletion of a type of stem cell called Lgr6+. These skin stem cells reside in the upper part of the hair follicle and participate in wound healing when tissue is damaged. Thus, aberrant alternative splicing by SRSF6 on the one hand increases cell proliferation, but on the other hand prevents the process by which proliferating cells mature. "The cells remain in an abnormal activation state that would otherwise be temporary during normal tissue repair. More studies are needed to understand this phenomenon in detail," says Mads Jensen, Ph.D., first author of the new paper who performed the experiments as a postdoctoral researcher in the Krainer lab.

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Overexpression of splicing protein in skin repair causes early changes seen in skin cancer

Jan. 16, 2014 The human body is daily exposed to external assaults such as bacteria, ultraviolet light or chemical agents. Skin, the largest organ of the body, is the first line of defense against these agents. Skin performs this function thanks to the close connections established between its cells (e.g. adherens junctions). The loss of cell adhesion between these cells is related to inflammatory diseases and cancer, hence the special interest in this area of research over the past years.

A study by the Spanish National Cancer Research Centre (CNIO), featured on the cover of the Journal of Cell Biology, shows how interactions between skin stem cells -- the cells responsible for the constant renewal of skin -- maintain the architecture of this organ. "We knew that these junctions were important in skin stem cells but the cellular components involved in their structure and function were not yet understood," says Mirna Prez-Moreno, head of the Epithelial Cellular Biology Group that led the study.

Using skin cells derived from mice, researchers have discovered that one of the key elements in the formation and stabilisation of these junctions are microtubules, tubular structures that are part of all cells and that serve as pillars to maintain their form and function.

"We have seen for the first time that skin stem-cell microtubules connect with cell-cell junctions to form velcro-like structures that hold the cells together," says Marta Shahbazi, a researcher on Prez-Moreno's team and the first author of the study.

The connection between these two cellular components -- microtubules and cell-cell junctions -- occurs via the interaction between the CLASP2 and p120 catenin proteins, linked to microtubules and cell junctions respectively.

"We found that the abscence of CLASP2 or p120 catenin in epidermal stem cells caused a loss of their adhesion, and therefore the structure of these cells," says Shahbazi.

"Our results will open up new paths for exploring how these proteins regulate skin physiology," says Prez-Moreno, adding that this knowledge will be "important for the possible development of future regenerative or anti cancer therapies."

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'Molecular scaffolding' found that maintains skin structure, organization

Durham, NC (PRWEB) January 17, 2014

A new assessment tool is helping scientists determine which treatments might benefit patients with a type of eye disorder called limbal stem cell deficiency (LSCD). The tool, developed by researchers at University College London and Moorfields Eye Hospital in London and funded by the UKs National Institute for Health Research Biomedical Research Centre at these institutions, has already shown that the majority of these patients can benefit in the short term from a stem cell transplantation and up to 30 percent are still experiencing better sight three years later, according to the study published in the current issue of STEM CELLS Translational Medicine.

LSCD is an eye disorder in which the stem cells responsible for forming the surface skin of the cornea are destroyed by injury or disease. This results in pain, loss of vision and a cosmetically unpleasant appearance. Many new treatments, including limbal stem cell transplants, are emerging for this condition but their effectiveness remains to be proven.

Assessing how well they perform has been severely hampered by the lack of biomarkers for LSCD and/or validated tools for determining its severity, said Alex Shortt, M.D., Ph.D., of University College Londons Institute of Ophthalmology and lead investigator in the study. In virtually all studies of limbal stem cell transplantation to date the clinical outcome has been assessed subjectively by the investigating clinician. This is clearly open to significant measurement and reporting bias.

His teams aims, then, were to design and test the reliability of a new tool for grading LSCD, to define a set of core outcome measures to use in evaluating treatments and to demonstrate the treatments impact on two common types of LSCD: a genetic disorder called aniridia and Stevens-Johnson syndrome (SJS), an inflammatory disorder.

They began developing an assessment tool by paring down a list of clinical signs taken from previously published studies to four key LSCD indicators: corneal epithelial haze, superficial corneal neovascularization, corneal epithelial irregularity and corneal epithelial defect. A standardized grading plate was then produced for each of these parameters, ranging from normal to severe. They named their assessment method the Clinical Outcome Assessment in Surgical Trials of Limbal stem cell deficiency [COASTL] tool and validated its performance in 26 patients with varying degrees of LSCD.

Once they had the COASTL tool in place, they used it to evaluate treatment outcomes in 14 patients with aniridia or SJS. All had undergone a limbal epithelial transplantation (allo-CLET), using cells taken from a deceased donor, cultivated in the lab before being transplanted into the recipient.

The COASTL tool showed that following allo-CLET there was a decrease in LSCD severity and an increase in visual acuity up to 12 months post-treatment, but thereafter LSCD severity and visual acuity progressively deteriorated, Dr. Shortt said. However, despite a recurrence of clinical signs, the visual benefit persisted in 30 percent of aniridic and 25 percent of SJS patients at 36 months.

A reliable method of obtaining objective outcome data for surgical trials of limbal stem cell deficiency will greatly contribute to the effective evaluation of current and new treatments, said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

The full article, Three-Year Outcomes of Cultured Limbal Epithelial Allografts in Aniridia and Stevens-Johnson Syndrome Evaluated Using the Clinical Outcome Assessment in Surgical Trials Assessment Tool, can be accessed at http://www.stemcellstm.com.

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New Assessment Tool Shows Potential of Stem Cells in Restoring LSCD Patients’ Sight

Stem cells have made headlines in the scientific and medical realms for over a decade, and with good reason. Some can grow into any type of cell in the body. The therapeutic potential is staggering, and researchers are working towards using stem cells to treat everything from diabetes to spinal cord injuries.

More recently, stem cell has emerged as a cosmetics industry buzzword, cropping up in product names, claims and ingredient lists. Stem cells seem ideal for anti-aging skincare, and stem cell products allude to stimulating the skin to grow new, younger cells and reverse wrinkling.

Despite products with names such as Stem Cell Therapy and StemCellin, or ingredients that include stem cell extract and stem cell conditioned media, none of the beauty creams actually contain stem cells. And, none are proven to affect your own stem cells.

MORE: The First Anti-Wrinkle Pill?

So, whats going on here? Whats in these products, if not stem cells? YouBeauty explains whats inside, why it could be dangerous and how stem cell beauty companies are skimping on science.

Meet the Stem Cells

Before we delve into the beauty creams, a brief biology lesson. Stem cells come in several varieties: embryonic (ESC), adult (ASC), induced pluripotent (iPSC) and human parthenogenetic (hpSC). All can develop into other cell types, or differentiate, but not all are created equal. And, just two relate to stem cell beauty products.

In research, ESCs come from embryos that are made from an egg fertilized outside the body, in vitro. Embryos develop from just a small cluster of cells into an entire body, thus ESCs have the potential to differentiate into nearly all cell types, from brain to heart to liver. This quality, called pluriopotency, means they could potentially be used to treat any type of diseased or injured organ or tissue.

QUIZ: How Healthy is Your Skin?

ESCs, besides being difficult to grow, face an ethical quandary: using them destroys embryos, which is why theyve ignited in political debate. In the past few years, researchers introduced two methods that attempt to mimic ESCs pluripotency sans embryo, which could eventually avoid these thorny issues. One uses a cocktail of genes to reprogram differentiated cells back into an ESC-like state (iPSC). The other uses human parthenogenetic (translation: virgin birth) embryos, which come from non-fertilized eggs, but retain some characteristics of a normal embryo (hpSC). But, ongoing research must confirm the characteristics and safety of both cell types before they can replace ESC in research. Theres a long way to go.

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Stem Cells in Skincare - YouBeauty.com

19 hours ago Mutant epidermal stem cells lose the connections to their neighbours (red, right) compared to normal stem cells (red, left). Credit: CNIO

The human body is daily exposed to external assaults such as bacteria, ultraviolet light or chemical agents. Skin, the largest organ of the body, is the first line of defense against these agents. Skin performs this function thanks to the close connections established between its cells (e.g. adherens junctions). The loss of cell adhesion between these cells is related to inflammatory diseases and cancer, hence the special interest in this area of research over the past years.

A study by the Spanish National Cancer Research Centre (CNIO), featured on the cover of the Journal of Cell Biology, shows how interactions between skin stem cellsthe cells responsible for the constant renewal of skinmaintain the architecture of this organ. "We knew that these junctions were important in skin stem cells but the cellular components involved in their structure and function were not yet understood", says Mirna Prez-Moreno, head of the Epithelial Cellular Biology Group that led the study.

Using skin cells derived from mice, researchers have discovered that one of the key elements in the formation and stabilisation of these junctions are microtubules, tubular structures that are part of all cells and that serve as pillars to maintain their form and function.

"We have seen for the first time that skin stem-cell microtubules connect with cell-cell junctions to form velcro-like structures that hold the cells together", says Marta Shahbazi, a researcher on Prez-Moreno's team and the first author of the study.

The connection between these two cellular componentsmicrotubules and cell-cell junctionsoccurs via the interaction between the CLASP2 and p120 catenin proteins, linked to microtubules and cell junctions respectively.

"We found that the abscence of CLASP2 or p120 catenin in epidermal stem cells caused a loss of their adhesion, and therefore the structure of these cells", says Shahbazi.

"Our results will open up new paths for exploring how these proteins regulate skin physiology", says Prez-Moreno, adding that this knowledge will be "important for the possible development of future regenerative or anti cancer therapies".

Explore further: Adult stem cells found to suppress cancer while dormant

Journal reference: Journal of Cell Biology

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Study finds a 'molecular scaffolding' that maintains skin structure and organisation

Cofounder of Stem Cell Theranostics and StartX Med Divya Nag is attacking one of medicine's biggest problems: the fact that most types of human cellslike those in the heart or liverdie when you keep them in a petri dish. This makes testing new drugs a risky, costly and time-consuming business: 90% of medicines that start clinical trials turn out to be too unsafe or ineffective to market. But a new technology, the induced pluripotent stem cell, may help. Nag's company, Stem Cell Theranostics, was created from technology funded by a $20 million grant from the California Institute of Regenerative Medicine and is closing a venture round. It turns cellsusually from a piece of skininto embryonic-like stem cells, then uses them to create heart cells. These cells can live in petri dishes and be used to test new drugs. Someday they might even replace heart tissue that dies during a heart attack. Three large pharmaceutical companies are customers, though revenues are small. Nag, who was already publishing in prestigious scientific journals when she was an undergraduate, dropped out of Stanford to pursue her dream. No regrets: "Our technology was so promising and I was so passionate about it that nothing else made sense to me," she says. "It was very clear this was what I wanted to do."

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2014 30 Under 30: Science & Healthcare

PUBLIC RELEASE DATE:

14-Jan-2014

Contact: Michelle Quivey mquivey@isscr.org 224-592-5012 International Society for Stem Cell Research

CHICAGO The International Society for Stem Cell Research (ISSCR) has announced the following 2014 award recipients, who will be formally recognized at its 12th Annual Meeting in Vancouver, taking place June 18-21, 2014:

The McEwen Award for Innovation, supported by the McEwen Centre for Regenerative Medicine, recognizes original thinking and groundbreaking research pertaining to stem cells or regenerative medicine that opens new avenues of exploration toward the understanding or treatment of human disease or affliction. The winner receives $100,000 USD. Past winners include James Thomson, Rudolf Jaenisch, Kazutoshi Takahashi and Shinya Yamanaka.

Award recipient Surani is a world leader in the field of epigenetics and the development of the mammalian germ line. His work on early mammalian development led to his involvement in the discovery of genomic imprinting and ongoing contributions to understanding the mechanistic basis of imprinting. Most relevant to stem cell biology, is his work on the cellular and molecular specification of the mammalian germ cell lineage, which impacted the field's understanding of how the germ line is established and the molecular mechanisms responsible for reprogramming the epigenome in order to generate the totipotent state.

"The ISSCR is thrilled to announce the McEwen Award for Innovation, our most prestigious award, will be presented to Azim Surani," Janet Rossant, ISSCR president, said. "His pioneering research, which has changed the face of epigenetics and advanced the field of stem cell biology, is a rare and significant contribution from a single individual."

The ISSCR-BD Biosciences Outstanding Young Investigator Award recognizes exceptional achievements by an ISSCR member and investigator in the early part of their independent career in stem cell research. The winner receives a $7,500 USD personal award and an opportunity to present at the ISSCR Annual Meeting. Past winners include Marius Wernig, Cdric Blanpain, Robert Blelloch, Joanna Wysocka and Konrad Hochedlinger.

Award recipient Greco established a noninvasive method to directly visualize skin stem cell division in real time in living animals the first of its kind for imaging any stem cell. By combining this method with laser ablation and transgenic lineage tracing, she captured previously inaccessible key information on stem cell behavior during tissue maintenance and regeneration. She demonstrated that the niche location of stem cells dictates their fates, the niche is required for tissue maintenance, and that a -catenin-mediated extrinsic mechanism regulates stem cell activation.

"The ISSCR is looking forward to presenting our Outstanding Young Investigator Award to Valentina Greco," Rossant said. "Her enthusiastic nomination by over a dozen leaders in the field of stem cell research demonstrates the significance of her early-career contributions to stem cell biology and regenerative medicine."

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The International Society for Stem Cell Research announces its 2014 award recipients

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Newswise While the ability of human embryonic stem cells (hESCs) to become any type of mature cell, from neuron to heart to skin and bone, is indisputably crucial to human development, no less important is the mechanism needed to maintain hESCs in their pluripotent state until such change is required.

In a paper published in this weeks Online Early Edition of PNAS, researchers from the University of California, San Diego School of Medicine identify a key gene receptor and signaling pathway essential to doing just that maintaining hESCs in an undifferentiated state.

The finding sheds new light upon the fundamental biology of hESCs with their huge potential as a diverse therapeutic tool but also suggests a new target for attacking cancer stem cells, which likely rely upon the same receptor and pathway to help spur their rampant, unwanted growth.

The research, led by principal investigator Karl Willert, PhD, assistant professor in the Department of Cellular and Molecular Medicine, focuses upon the role of the highly conserved WNT signaling pathway, a large family of genes long recognized as a critical regulator of stem cell self-renewal, and a particular encoded receptor known as frizzled family receptor 7 or FZD7.

WNT signaling through FZD7 is necessary to maintain hESCs in an undifferentiated state, said Willert. If we block FZD7 function, thus interfering with the WNT pathway, hESCs exit their undifferentiated and pluripotent state.

The researchers proved this by using an antibody-like protein that binds to FZD7, hindering its function. Once FZD7 function is blocked with this FZD7-specific compound, hESCs are no longer able to receive the WNT signal essential to maintaining their undifferentiated state.

FZD7 is a so-called onco-fetal protein, expressed only during embryonic development and by certain human tumors. Other studies have suggested that FZD7 may be a marker for cancer stem cells and play an important role in promoting tumor growth. If so, said Willert, disrupting FZD7 function in cancer cells is likely to interfere with their development and growth just as it does in hESCs.

Willert and colleagues, including co-author Dennis Carson, MD, of the Sanford Consortium for Regenerative Medicine and professor emeritus at UC San Diego, plan to further test their FZD7-blocking compound as a potential cancer treatment.

Excerpt from:
Keeping Stem Cells Pluripotent

Abstract

The skin constantly renews itself throughout adult life, and the hair follicle undergoes a perpetual cycle of growth and degeneration. Stem cells (SCs) residing in the epidermis and hair follicle ensure the maintenance of adult skin homeostasis and hair regeneration, but they also participate in the repair of the epidermis after injuries. We summarize here the current knowledge of epidermal SCs of the adult skin. We discuss their fundamental characteristics, the methods recently designed to isolate these cells, the genes preferentially expressed in the multipotent SC niche, and the signaling pathways involved in SC niche formation, SC maintenance, and activation. Finally, we speculate on how the deregulation of these pathways may lead to cancer formation.

Keywords: hair follicle, multipotency, self-renewal, cell fate determination, Wnt signaling, Bmp, cancer

Skin and its appendages ensure a number of critical functions necessary for animal survival. Skin protects animals from water loss, temperature change, radiation, trauma, and infections, and it allows animals to perceive their environment through tactile sense. Through camouflage, the skin provides protection against predators, and it also serves as decoration for social and reproductive behavior.

Adult skin is composed of a diverse organized array of cells emanating from different embryonic origins. In mammals, shortly after gastrulation, the neurectoderm cells that remain at the embryo surface become the epidermis, which begins as a single layer of unspecified progenitor cells. During development, this layer of cells forms a stratified epidermis (sometimes called interfollicular epidermis), the hair follicles (HRs), sebaceous glands, and, in nonhaired skin, the apocrine (sweat) glands. Mesoderm-derived cells contribute to the collagen-secreting fibroblasts of the underlying dermis, the dermovasculature that supplies nutrients to skin, arrector pili muscles that attach to each hair follicle (HF), the subcutaneous fat cells, and the immune cells that infiltrate and reside in the skin. Neural crestderived cells contribute to melanocytes, sensory nerve endings of the skin, and the dermis of the head. Overall, approximately 20 different cell types reside within the skin.

In the adult, many different types of stem cells (SCs) function to replenish these various cell types in skin as it undergoes normal homeostasis or wound repair. Some SCs (e.g., those that replenish lymphocytes) reside elsewhere in the body. Others (e.g., melanoblasts and epidermal SCs) reside within the skin itself. This review concentrates primarily on epidermal SCs, which possess two essential features common to all SCs: They are able to self-renew for extended periods of time, and they differentiate into multiple lineages derived from their tissue origin (Weissman et al. 2001).

Mature epidermis is a stratified squamous epithelium whose outermost layer is the skin surface. Only the innermost (basal) layer is mitotically active. The basal layer produces, secretes, and assembles an extracellular matrix (ECM), which constitutes much of the underlying basement membrane that separates the epidermis from the dermis. The most prominent basal ECM is laminin5, which utilizes 31-integrin for its assembly. As cells leave the basal layer and move outward toward the skin surface, they withdraw from the cell cycle, switch off integrin and laminin expression, and execute a terminal differentiation program. In the early stages of producing spinous and granular layers, the program remains transcriptionally active. However, it culminates in the production of dead flattened cells of the cornified layer (squames) that are sloughed from the skin surface, continually being replaced by inner cells moving outward ().

Epidermal development and hair follicle morphogenesis. The surface of the early embryo is covered by a single layer of ectodermal cells that adheres to an underlying basement membrane of extracellular matrix. As development proceeds, the epidermis progressively ...

The major structural proteins of the epidermis are keratins, which assemble as obligate heterodimers into a network of 10-nm keratin intermediate filaments (IFs) that connect to 64-integrin-containing hemidesmosomes that anchor the base of the epidermis to the laminin5-rich, assembled ECM. Keratin IFs also connect to intercellular junctions called desmosomes, composed of a core of desmosomal cadherins. Together, these connections to keratin IFs provide an extensive mechanical framework to the epithelium (reviewed in Omary et al. 2004). The basal layer is typified by the expression of keratins K5 and K14 (also K15 in the embryo), whereas the intermediate suprabasal (spinous) layers express K1 and K10. Desmosomes connected to K1/K10 IFs are especially abundant in suprabasal cells, whereas basal cells possess a less robust network of desmosomes and K5/K14. Rather, basal cells utilize a more dynamic cytoskeletal network of microtubules and actin filaments that interface through -and -catenins to E-cadherin-mediated cell-cell (adherens) junctions, in addition to the 1-integrin-mediated cell-ECM junctions (reviewed in Green et al. 2005, Perez-Moreno et al. 2003). Filaggrin and loricrin are produced in the granular layer. The cornified envelope seals the epidermal squames and provides the barrier that keeps microbes out and essential fluids in (Candi et al. 2005, Fuchs 1995) (). The program of terminal differentiation in the epidermis is governed by a number of transcription factor families, including AP2, AP1, C/EBPs, Klfs, PPARs, and Notch (reviewed in Dai & Segre 2004).

Although the molecular mechanisms underlying the process of epidermal stratification are still unfolding, several studies have recently provided clues as to how this might happen. Increasing evidence suggests the transcription factor p63 might be involved. Mice null for the gene encoding p63 present an early block in the program of epidermal stratification (Mills et al. 1999, Yang et al. 1999).

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Epidermal Stem Cells of the Skin

PUBLIC RELEASE DATE:

9-Jan-2014

Contact: Robert Miranda cogcomm@aol.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Putnam Valley, NY. (Jan. 9, 2014) Using skin-derived stem cells (SDSCs) and a previously developed collagen tube designed to successfully bridge gaps in injured nerves in rat models, the research team in Milan, Italy that established and tested the procedure has successfully rescued peripheral nerves in the upper arms of a patient suffering peripheral nerve damage who would have otherwise had to undergo amputations.

The study will be published in a future issue of Cell Transplantation but is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-ct1096.

"Peripheral nerve repair with satisfactory functional recovery remains a great surgical challenge, especially for severe nerve injuries resulting in extended nerve defects," said study corresponding author Dr. Yvan Torrente, of the Department of Pathophysiology and Transplantation at the University of Milan. "However, we hypothesized that the combination of autologous (self-donated) SDSCs placed in collagen tubes to bridge gaps in the damaged nerves would restore the continuity of injured nerves and save from amputation the upper arms of a patient with poly-injury to motor and sensory nerves."

Although autologous nerve grafting has been the 'gold standard' for reconstructive surgeries, these researchers felt that there were several drawbacks to that approach, including graft availability, donor site morbidity, and neuropathic pain.

According to the researchers, autologous SDSCs have advantages over other stem cells as they are an accessible source of stem cells rapidly expandable in culture, and capable of survival and integration within host tissues.

While the technique of using the collagen tubes - NeuraGen, an FDA-approved device - to guide the transplanted cells over gaps in the injured nerve had been previously developed and tested by the same researchers with the original research successfully saving damaged sciatic nerves on rats, the present case, utilizing the procedure they developed employing SDSCs and a nerve guide, is the first to be carried out on a human.

Over three years, the researchers followed up on the patient, assessing functional recovery of injured median and ulnar nerves by pinch gauge test and static two-point discrimination and touch test with monofiliments along with electrophysiological and MRI examinations.

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Stem cells injected into nerve guide tubes repair injured peripheral nerve

16 hours ago This is a set of chromosomes in haploid mouse embryonic stem cells. Credit: Martin Leeb

A fast and comprehensive method for determining the function of genes could greatly improve our understanding of a wide range of diseases and conditions, such as heart disease, liver disease and cancer.

The method uses stem cells with a single set of chromosomes, instead of the two sets found in most cells, to reveal what causes the "circuitry" of stem cells to be rewired as they begin the process of conversion into other cell types. The same method could also be used to understand a range of biological processes.

Embryonic stem cells rely on a particular gene circuitry to retain their original, undifferentiated state, making them self-renewing. The dismantling of this circuitry is what allows stem cells to start converting into other types of cells - a process known as cell differentiation - but how this happens is poorly understood.

Researchers from the University of Cambridge Wellcome Trust-MRC Stem Cell Institute have developed a technique which can pinpoint the factors which drive cell differentiation, including many that were previously unidentified. The method, outlined in the Thursday (9 January) edition of the journal Cell Stem Cell, uses stem cells with a single set of chromosomes to uncover how cell differentiation works.

Cells in mammals contain two sets of chromosomes one set inherited from the mother and one from the father. This can present a challenge when studying the function of genes, however: as each cell contains two copies of each gene, determining the link between a genetic change and its physical effect, or phenotype, is immensely complex.

"The conventional approach is to work gene by gene, and in the past people would have spent most of their careers looking at one mutation or one gene," said Dr Martin Leeb, who led the research, in collaboration with Professor Austin Smith. "Today, the process is a bit faster, but it's still a methodical gene by gene approach because when you have an organism with two sets of chromosomes that's really the only way you can go."

Dr Leeb used unfertilised mouse eggs to generate embryonic stem cells with a single set of chromosomes, known as haploid stem cells. These haploid cells show all of the same characteristics as stem cells with two sets of chromosomes, and retain the same full developmental potential, making them a powerful tool for determining how the genetic circuitry of mammalian development functions.

The researchers used transposons "jumping genes" to make mutations in nearly all genes. The effect of a mutation can be seen immediately in haploid cells because there is no second gene copy. Additionally, since embryonic stem cells can convert into almost any cell type, the haploid stem cells can be used to investigate any number of conditions in any number of cell types. Mutations with important biological effects can then rapidly be traced to individual genes by next generation DNA sequencing.

"This is a powerful and revolutionary new tool for discovering how gene circuits operate," said Dr Leeb. "The cells and the methodology we've developed could be applied to a huge range of biological questions."

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Rewiring stem cells

Researchers have developed a new way to study bone disorders and bone growth, using stem cells from patients afflicted with a rare, genetic bone disease. The approach, based on Nobel-Prize winning techniques, could illuminate the illness, in which muscles and tendons progressively turn into bone, and addresses the similar destructive process that afflicts a growing number of veterans who have suffered blast injuries including traumatic amputations or injuries to the brain and nervous system. This insidious hardening of tissues also grips some patients following joint replacement or severe bone injuries.

The disease model, described in a new study by a UC San Francisco-led team, involves taking skin cells from patients with the bone disease, reprogramming them in a lab dish to their embryonic state, and deriving stem cells from them.

Edward Hsiao, MD, PhD

Once the team derived the stem cells, they identified a cellular mechanism that drives abnormal bone growth in the thus-far untreatable bone disease, calledfibrodysplasiaossificansprogressiva(FOP). Furthermore, they found that certain chemicals could slow abnormal bone growth in the stem cells, a discovery that might help guide future drug development.

Clinically, the genetic and trauma-caused conditions are very similar, with bone formation in muscle leading to pain and restricted movement, according to the leader of the new study, Edward Hsiao, MD, PhD, an endocrinologist who cares for patients with rare and unusual bone diseases at the UCSF Metabolic Bone Clinic in the Division of Endocrinology and Metabolism.

The human cell-based disease model is expected to lead to a better understanding of these disorders and other illnesses, Hsiao said.

The new FOP model already has shed light on the disease process in FOP by showing that the mutated gene can affect different steps of bone formation, Hsiao said. These different stages represent potential targets for limiting or stopping the progression of the disease, and may also be useful for blocking abnormal bone formation in other conditions besides FOP. The human stem-cell lines we developed will be useful for identifying drugs that target the bone-formation process in humans."

The teams development of, and experimentation with, the human stem-cell disease model for FOP, published in the December issue of theOrphanetJournal of Rare Diseases, is a realization of the promise of research using stem cells of the type known as induced pluripotent stem (iPS) cells, immortal cells of nearly limitless potential, derived not from embryos, but from adult tissues.

Shinya Yamanaka, MD, PhD, a UCSF professor of anatomy and a senior investigator with the UCSF-affiliated Gladstone Institutes, as well as the director of the Center foriPSCell Research and Application (CiRA) and a principal investigator at Kyoto University, shared the Nobel Prize in 2012 for discovering how to makeiPScells from skin cells using a handful of protein factors. These factors guide a reprogramming process that reverts the cells to an embryonic state, in which they have the potential to become virtually any type of cell.

Link:
Stem Cells Used to Model Disease that Causes Abnormal Bone Growth

PUBLIC RELEASE DATE:

7-Jan-2014

Contact: David McKeon DMckeon@nyscf.org 212-365-7440 New York Stem Cell Foundation

NEW YORK, NY (January 7, 2014) Scientists at The New York Stem Cell Foundation (NYSCF) Research Institute, working in collaboration with scientists from Columbia University Medical Center (CUMC), for the first time generated induced pluripotent stem (iPS) cells lines from non-cryoprotected brain tissue of patients with Alzheimer's disease.

These new stem cell lines will allow researchers to "turn back the clock" and observe how Alzheimer's develops in the brain, potentially revealing the onset of the disease at a cellular level long before any symptoms associated with Alzheimer's are displayed. These reconstituted Alzheimer's cells will also provide a platform for drug testing on cells from patients that were definitively diagnosed with the disease. Until now, the only available method to definitively diagnose Alzheimer's disease that has been available to researchers is examining the brain of deceased patients. This discovery will permit scientists for the first time to compare "live" brain cells from Alzheimer's patients to the brain cells of other non-Alzheimer's patients.

NYSCF scientists successfully produced the iPS cells from frozen tissue samples stored for up to eleven years at the New York Brain Bank at Columbia University.

This advance, published today in Acta Neuropathologica Communications , shows that disease-specific iPS cells can be generated from readily available biobanked tissue that has not been cryoprotected, even after they have been frozen for many years. This allows for the generation of iPS cells from brains with confirmed disease pathology as well as allows access to rare patient variants that have been banked. In addition, findings made using iPS cellular models can be cross-validated in the original brain tissue used to generate the cells. The stem cell lines generated for this study included samples from patients with confirmed Alzheimer's disease and four other neurodegenerative diseases.

This important advance opens up critical new avenues of research to study cells affected by disease from patients with definitive diagnoses. This success will leverage existing biobanks to support research in a powerful new way.

iPS cells are typically generated from a skin or blood sample of a patient by turning back the clock of adult cells into pluripotent stem cells, cells that can become any cell type in the body. While valuable, iPS cells are often generated from patients without a clear diagnosis of disease and many neurodegenerative diseases, such as Alzheimer's disease, often lack specific and robust disease classification and severity grading. These diseases and their extent can only be definitively diagnosed by post-mortem brain examinations. For the first time we will now be able to compare cells from living people to cells of patients with definitive diagnoses generated from their banked brain tissue.

Brain bank networks, which combined contain tens of thousands of samples, provide a large and immediate source of tissue including rare disease samples and a conclusive spectrum of disease severity among samples. The challenge to this approach is that the majority of biobanked brain tissue was not meant for growing live cells, and thus was not frozen in the presence of cryoprotectants normally used to protect cells while frozen. NYSCF scientists in collaboration with CUMC scientists have shown that these thousands of samples can now be used to make living human cells for use in disease studies and to develop new drugs or preventative treatments for future patients.

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NYSCF scientists make living brain cells from Alzheimer's patients biobanked brain tissue

Despite some ethical concerns, most patients are now broadly endorsing stem cell research.

In the case of induced pluripotent stem cells (iPSCs), which are stem cells made from skin or other tissues, researchers at the Johns Hopkins University found patients were largely in favour of participating in iPSC research even if personal benefit was unlikely.

The patients, however, raised concerns about consent, privacy and transparency.

"Bioethicists as well as stem cell researchers and policy-makers have discussed ethical issues at length but till date, we didn't have any systematic information about what patients think about these issues," said Jeremy Sugarman, the Harvey M. Meyerhoff professor of bioethics and medicine at Johns Hopkins Berman Institute of Bioethics.

Unlike human embryonic stem cells, iPSCs are derived without destroying a human embryo. Research with human iPSCs is valuable for developing new drugs, studying disease, and perhaps developing medical treatments, said the study published in the journal Cell Stem Cell.

According to the study, consent was highly important for patients. Some patients even suggested that proper informed consent could compensate for other concerns they had about privacy, the "immortalisation" of cells and the commercialisation of stem cells.

There was a "strong desire among participants to have full disclosure of the anticipated uses, with some participants wanting to be able to veto certain uses of their cells", the study added.

"The idea that donated cells would potentially live forever was unnerving to some participants," the report stated.

"This study is a first step in getting crucial information about what values are factored into a decision to participate in iPSC research, and what those participants expect from the experience," said Sugarman.

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Patients endorse key stem cell research

Cellogica
Cellogica is a non-greasy formula that uses revolutionary stem cell technology to regenerate new skin stem cells, prevent the loss of existing skin stem cell...

By: Jordan Kaleb

Originally posted here:
Cellogica - Video

MADISON--After Susan Derse Phillips had chemotherapy for leukemia, she received a stem cell transplant, getting blood-forming cells from a donor to restore her immune system and attack any remaining leukemia cells.

The procedure apparently cured her leukemia, a type of blood cancer. But her skin turned red, her mouth and eyes became dry and she developed diarrhea, fatigue, bronchitis and pneumonia.

She had graft-versus-host disease, or GVHD, a life-threatening complication of the transplant. Her donors cells the graft werent attacking just her leukemia. They were attacking her skin, her gut, her lungs and other organs essentially, her body, the host.

It got pretty scary pretty quickly, said Phillips, 66, of Madison, who continues to struggle with the condition two years after the transplant.

More than half of patients who get donor stem cell transplants develop GVHD, and at least 20 percent of them die from it, said Dr. Mark Juckett, a hematologist at UW Health. But the complication, which likely is under-reported, receives relatively little attention.

Phillips, former president and CEO of Agrace HospiceCare in Fitchburg, set out to change that in Wisconsin. With $500,000 from two donors as seed money, she persuaded UW Health to launch a program to focus on the condition.

UW Carbone Cancer Centers new GVHD program aims to provide better treatment for the 250 or so UW Health patients with the condition and up to 1,000 such patients in Wisconsin and parts of neighboring states, said Juckett, one of the programs two leaders. The program will also study ways to prevent GVHD.

Too often, when doctors give donor stem cell transplants, were trading one disease for another, said Juckett, Phillips doctor. Theres been a lot of focus on how best to do the transplant ... but theres never been a real recognition of dealing with GHVD as a real problem.

Nationwide, about 18,500 stem cell or bone marrow transplants were performed in 2011, according to the Center for International Blood and Marrow Transplant Research in Milwaukee.

At UW Hospital, about 150 patients receive the transplants each year. Roughly 100 of them get infusions of their own stem cells, after high-dose chemotherapy or radiation, for conditions such as multiple myeloma and non-Hodgkins lymphoma. They are not at risk for GVHD.

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Stem cell transplant complication gains attention at UW Health

A release from the University of California-Los Angleles written by Shaun Mason reports that researchers at UCLA's Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have discovered a mechanism by which certain adult stem cells suppress their ability to initiate skin cancer during their dormant phase an understanding that could be exploited for better cancer-prevention strategies. The study, led by Andrew White and William Lowry, was published online Decemeber 15th 2013 in the journal Nature Cell Biology.

The release notes that hfollicle stem cells, the tissue-specific adult stem cells that generate the hair follicles, are also the cells of origin for cutaneous squamous cell carcinoma, a common skin cancer. These stem cells cycle between periods of activation during which they can grow and quiescence (when they remain dormant).

White and Lowry applied known cancer-causing genes to hair follicle stem cells of laboratory mice and found that during the cells dormant phase, they could not initiate skin cancer. Once the cells were in their active period, however, they began growing cancer.

The release quotes White as saying, "We found that this tumor suppression via adult stem cell quiescence was mediated by PTEN, a gene important in regulating the cell's response to signaling pathways. Therefore, stem cell quiescence is a novel form of tumor suppression in hair follicle stem cells, and PTEN must be present for the suppression to work."

The team believes that understanding cancer suppression through quiescence could better inform preventative strategies for certain patients, such as organ transplant recipients, who are particularly susceptible to squamous cell carcinoma, and for those taking the drug vemurafenib for melanoma, another type of skin cancer. The study also may reveal parallels between squamous cell carcinoma and other cancers in which stem cells have a quiescent phase.

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Dormant Adult Stem Cells Suppress Cancer

MELBOURNE: Doctors may soon be able to draw new bone, skin and muscle on to patients, after scientists created a pen-like device that can apply human cells directly on to seriously injured people.

The device contains stem cells and growth factors and will give surgeons greater control over where the materials are deposited.

It will also reduce the time the patient is in surgery by delivering live cells and growth factors directly to the site of injury, accelerating the regeneration of functional bone and cartilage, scientists said.

The device developed at the University of Wollongong (UOW) will eliminate the need to harvest cartilage and grow it for weeks in a lab.

The Bio Pen works similar to 3D printing methods by delivering cell material inside a bio-polymer such as alginate, a seaweed extract, protected by a second, outer layer of gel material.

The two layers of gel are combined in the pen head as it is extruded onto the bone surface and the surgeon draws with the ink to fill in the damaged bone section.

A low powered ultra-violet light source is fixed to the device that solidifies the inks during dispensing, providing protection for the embedded cells while they are built up layer-by-layer to construct a 3D scaffold in the wound site.

Once the cells are drawn onto the surgery site they will multiply, become differentiated into nerve cells, muscle cells or bone cells and will eventually turn from individual cells into a thriving community of cells in the form of a functioning a tissue, such as nerves, or a muscle.

The device can also be seeded with growth factors or other drugs to assist regrowth and recovery, while the hand-held design allows for precision in theatre and ease of transportation.

The BioPen prototype was designed and built using the 3D printing equipment in the labs at Wollongong and was handed over to clinical partners at St Vincents Hospital Melbourne, led by Professor Peter Choong, who will work on optimising the cell material for use in clinical trials.

Read more:
New pen-like device to repair broken bone

The breakthrough could also provide the key to skin generation for burn victims and skin cancer sufferers, according to a team at the University of Southern California

Bald men could have a full head of hair after the discovery of the gene that promotes hair growth.

The breakthrough could also provide the key to skin generation for burn victims and skin cancer sufferers.

A team at the University of Southern California investigated stem cells found in follicles which can regenerate hair and skin.

Stem cell specialist Dr Krzysztof Kobielak said: Collectively, these new discoveries advance basic science and, more importantly, might translate into novel therapeutics for various human diseases.

Since BMP signaling has a key regulatory role in maintaining the stability of different types of adult stem cell populations, the implication for future therapies might be potentially much broader than baldness - and could include skin regeneration for burn patients and skin cancer.

The papers were published in the journals Stem Cells and the Proceedings of the National Academy of Sciences (PNAS).

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Bald Celebrities

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Cure for baldness could be near after discovery of gene that promotes hair growth

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Link:
Skin Stem Cell Serum, 1 oz - LifeExtension.com

Sci-Tech Technology News

The kidney as seen in a petri dish. Photo: UQ

A mini-kidney has been grown in an Australian laboratory from what were originally skin cells, boosting hopes for the future treatment of kidney disease.

The study adds support to a science-fiction-like goal of taking skin cells from a patient, using them to grow a kidney and then implanting it into the same patient, circumventing problems with transplant rejection.

The result of the work was a kidney measuring in the millimetres. The next step will be finding ways to increase its size.

The team who grew the mini-kidney: Professor Melissa Little, Dr Jessica Vanslambrouck and Dr Minoru Takasato. Photo: UQ

Lead researcher Professor Melissa Little spent years researching which genes were switched on or off during natural kidney development.

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The team manipulated skin cells that had been effectively turned into embryonic stem cells so that they began to "self-organise", arranging themselves into complex structures.

Professor Brandon Wainwright, the director of the Institute for Molecular Bioscience at the University of Queensland, where the study was conducted, said this was the first time self-organisation has been observed in a kidney.

See the article here:
Australian scientists grow mini-kidney in lab

December 20, 2013

redOrbit Staff & Wire Reports Your Universe Online

Regenerative medicine research conducted throughout this year at the University of Southern California (USC) could lead to new ways to counter baldness and receding hairlines using stem cells.

USC Assistant Professor of Pathology Dr. Krzysztof Kobielak and his colleagues have published a trio of papers in the journals Stem Cells and the Proceedings of the National Academy of Sciences (PNAS) describing some of the biological factors responsible for when hair starts growing, when it stops, and when it falls out.

According to USC, the three studies focused on stem cells that are located in adult hair follicles. Those cells, known as hfSCs, can regenerate both hair follicles and skin, and are governed by bone morphogenetic proteins (BMPs) and the Wnt signaling pathways groups of molecules that work together in order to control the cycles of hair growth and other cellular functions.

The most recent paper, published in the journal Stem Cells in November 2013, focuses on how the gene Wnt7b activates hair growth. Without Wnt7b, hair is much shorter, the team said. Kobielaks team originally proposed Wnt7bs role in a study published this January in PNAS. That paper identified a complex network of genes, including the Wnt and BMP signaling pathways, which controls the cycles of hair growth.

Reduced BMP signaling and increased Wnt signaling activate hair growth, while increased BMP signaling and decreased Wnt signaling keeps the hfSCs in a resting state, the researchers explained. The third paper, published in Stem Cells in September, sheds new light on the BMP signaling pathway. It looked at the function of the proteins Smad1 and Smad 5, which send and receive signals that regulate hair-related stem cells during growth periods.

Collectively, these new discoveries advance basic science and, more importantly, might translate into novel therapeutics for various human diseases, Kobielak explained. Since BMP signaling has a key regulatory role in maintaining the stability of different types of adult stem cell populations, the implication for future therapies might be potentially much broader than baldness and could include skin regeneration for burn patients and skin cancer.

Other USC researchers involved in the studies include postdoctoral fellow Eve Kandyba, Yvonne Leung, Yi-Bu Chen, Randall Widelitz, Cheng-Ming Chuong, Virginia M. Hazen, Agnieszka Kobielak, and Samantha J. Butler. Funding for the research was provided by the Donald E. and Delia B. Baxter Foundation Award and National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH).

Source: redOrbit Staff & Wire Reports - Your Universe Online

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Stem Cell Research Could Lead To A Cure For Baldness, And More