Archive for the ‘Skin Stem Cells’ Category

System for marking slow-cycling SCs in vivo and monitoring their fate. (A) Strategy. (B to D) Skin sections of mice before and after 4-week chase. Shown are epifluorescence of H2B-GFP (green) and 4,6-diamidino-2-phenylindole (DAPI) (blue), and indirect immunofluorescence with antibodies (Abs) indicated (Texas Red). The hair cycle stage is indicated on each set of after chase frames (see also fig. S1, B to D, and fig. S2). Arrows (B) denote Ki67+ sebaceous gland cells in telogen. Arrowheads [(B) and (C)] denote transition zone between bulge and newly generated follicle downgrowth. Late anagen (Ki67 in red): GFP-bright cells are retained in the bulge; their progeny rapidly divide, diluting H2B-GFP. (D) Early anagen II bulb overexposed for GFP and double-labeled (small arrowheads) with Abs against each differentiation cell type. (E) Mice after chase were scratch-wounded and analyzed by immunofluorescence. Arrows denote likely directions of movements of GFP-positive LRCs and progeny. Abbreviations: Bu, bulge; DP, dermal papilla; Mx, matrix; hg, hair germ; Ep, epidermis; asterisk, hair shaft (autofluorescent); hf, hair follicle; Cx, cortex; ORS/IRS, outer/inner root sheaths; BM, basement membrane; In, infundibulum; W, wound. Scale bars, 50 m.

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Defining the epithelial stem cell niche in skin.

Manhattan NY (PRWEB) December 13, 2014

ABRING, one of the pioneers in the new era of the most advanced skin care trend, announced the debut of their two new skin care products: ABRING lemon stem cell acne serum and ABRING apple stem cell serum/eyes serum, These two new cutting-edge skin care products contain concentrated essence which is derived from Californias organic plants and has no artificial or chemical components. This condensed essence has been widely recognized for its obvious effect on anti-aging and stimulation of skin cells regeneration. As a result, ABRINGs new stem cell products not only have such distinctive functions as anti-aging, supplementing moisture, alleviating scars appearance and whitening skin, but also can be safely used by pregnant women since it only contains pure natural plant ingredients.

It is well-known that the skin is exposed to all kinds of radiations everyday which can damage our skin in various ways. Most people think that there is nothing to worry because they have already used segregation frost. However, what they dont realize is the fact that segregation frost only plays a trivial role in isolation and doesnt help repair or stimulate skin cells renewal or regeneration activities.

Stem cells are capable of self-reproducing and have lots of potentials. Under different conditions, they can evolve into various functional cells. Therefore, the activity of skin stem cells directly affects the external appearance of the skin. ABRING uses the newest stem cell research achievement and is a known brand for natural beauty products. Because it contains condensed essences concentrated from organic plants and is free of any chemicals, ABRING can stimulate activity in skin cells, slow down the aging process, increase elasticity, improve tone, and reduce the appearance of scars. In addition, because ABRING also contains a lot of mineral water and vitamin C, it can effectively improve skin brightening and help cure and prevent acne.

ABRING products founder, Albert, born in California, United, is a cell biologist and a biochemist. Unlike many, he didnt have a carefree and happy childhood as the result of a natural disaster. However, Albert wasnt defeated by the unpredicted distress. Instead, he was dedicated to study and graduated from Columbia University. In 1971, invited by the U.S. government, Doctor Albert became one of first post-war medical doctors. In same year, Doctor Albert established ABRING laboratory which stands for: Doctor Albert brings hope. Based on years of research at Columbia University focusing on stem cell biology, Doctor Albert found that certain raw materials can effectively remove skin scars without using any chemical additives. After over 7000 experiments, he finally extracted pure activating factors from natural plants that can help alleviate the appearance of scars. Dr. Albert named the condensed essence of concentration of plant stem cells as ABRING. Since then, with its innovative and effective way of enhancing the tone of skin, ABRING started to be recognized more and more by the world. Doctor Albert's efforts eventually got paid off and ABRING became one of the favored skin care products from the users of all classes. Nowadays, ABRING has been used by more than 500 famous beauty salons over the world. Moreover, the product has been widely recommended by doctors as daily lotion for skin disease treatment or post-surgery care.

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ABRING Announces Debut of Stem Cell Based Skin Care Products

Nik Spencer/Nature

Eggs and sperm do it when they combine to make an embryo. John Gurdon did it in the 1960s, when he used intestinal cells from tadpoles to generate genetically identical frogs. Ian Wilmut did it too, when he used an adult mammalian cell to make Dolly the sheep in 1996. Reprogramming reverting differentiated cells back to an embryonic state, with the extraordinary ability to create all the cells in the body has been going on for a very long time.

Scientific interest in reprogramming rocketed after 2006, when scientists showed that adult mouse cells could be reprogrammed by the introduction of just four genes, creating what they called induced pluripotent stem (iPS) cells1. The method was simple enough for almost any lab to attempt, and now it accounts for more than a thousand papers per year. The hope is that pluripotent cells could be used to repair damaged or diseased tissue something that moved closer to reality this year, when retinal cells derived from iPS cells were transplanted into a woman with eye disease, marking the first time that reprogrammed cells were transplanted into humans (see Nature http://doi.org/xhz; 2004).

There is just one hitch. No one, not even the dozen or so groups of scientists who intensively study reprogramming, knows how it happens. They understand that differentiated cells go in, and pluripotent cells come out the other end, but what happens in between is one of biology's impenetrable black boxes. We're throwing everything we've got at it, says molecular biologist Knut Woltjen of the Center for iPS Cell Research and Application at Kyoto University in Japan. It's still a really confusing process. It's very complicated, what we're doing.

Kerri Smith talks to researcher Andras Nagy and reporter David Cyranoski about reprogramming cells.

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One of the problems, stem-cell biologists say, is that their starting population contains a mix of cells, each in a slightly different molecular state. And the process for making iPS cells is currently inefficient and variable: only a tiny fraction end up fully reprogrammed and even these may differ from one another in subtle but important ways. What is more, the path to reprogramming may vary depending on the conditions under which cells are being grown, and from one lab to the next. This makes it difficult to compare experimental results, and it raises safety concerns should a mix of poorly characterized cells be used in the clinic.

But new techniques are starting to clarify the picture. By carrying out meticulous analyses of single cells and amassing reams of detailed molecular data, biologists are identifying a number of essential events that take place en route to a reprogrammed state. This week, the biggest such project an international collaboration audaciously called Project Grandiose unveiled its results26. The scientists involved used a battery of tests to take fine-scale snapshots of every stage of reprogramming and in the process, revealed an alternative state of pluripotency. It was the first high-resolution analysis of change in cell state over time, says Andras Nagy, a stem-cell biologist at Mount Sinai Hospital in Toronto, Canada, who led the project. I'm not shy about saying grandiose.

I'm not shy about saying grandiose.

But there is more to do if scientists want to control the process well enough to generate therapeutic cells with ease. Yes, we can make iPS cells and yes we can differentiate them, but I think we feel that we do not control them enough says Jacob Hanna, a stem-cell biologist at the Weizmann Institute of Science in Rehovot, Israel. Controlling cell behaviour at will is very cool. And the way to do it is to understand their molecular biology with great detail.

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Stem cells: The black box of reprogramming

TIME Health medicine This New Kind of Stem Cell May Revolutionize How We Treat Diseases Scientists have created a new type of stem cell that could speed treatments for diseases and make them safer

Ever since Japanese researcher Shinya Yamanaka found a way to treat skin cells with four genes and reprogram them back to their embryonic state, scientists have been buzzing over the promise of stem cell therapies. Stem cells can be coaxed to become any of the bodys cell types, so they could potentially replace diseased or missing cells in conditions such as diabetes or Alzheimers. And Yamanakas method also meant that these cells could be made from patients themselves, so they wouldnt trigger dangerous immune rejections.

Now scientists led by Dr. Andras Nagy at Mount Sinai Hospital Lunenfeld-Tannenbaum Research Institute in Toronto report an exciting new advance that could push stem cells even closer to the clinic. In a series of papers in the journals Nature and Nature Communications, the group describes a new class of stem cell, which they called F class, that they generated in the lab.

The F class cells, says Nagy, have a few advantages over the Yamanaka-generated induced pluripotent stem cells, or iPS cells. While the iPS cells are created by using viruses to introduce four genes that reprogram the cells, Nagys team relied on a technique they developed several years ago using transposonssmall pieces of DNA that can insert themselves into different parts of a genome. Unlike viruses, these transposons can be popped out of the genome if theyre no longer needed, and they dont carry the potential risk of viral infection.

MORE: Stem-Cell Research: The Quest Resumes

Nagys team found that the transposons were much more reliable vehicles for delivering the reprogramming genes exactly where they were needed to efficiently turn the clock back on the skin cells. Whats more, they could use the common antibiotic doxycycline to turn the four genes on and off; adding doxycycline to the cell culture would trigger the transposons to activate, thus turning on the genes, while removing the antibiotic would turn them off.

In this way, says Nagy, he was able to pump up the efficiency of the reprogramming process. Using the Yamanaka method, it was hit-or-miss whether the viruses would find their proper place in a cells genome, and more uncertainty over how effectively it could direct the cell to activate the four reprogramming genes. F class cells are much more similar [in the culture dish], like monozygotic twins while iPS cells are more like brothers and sisters, he says.

That consistency is a potential advantage of the transposon method, since any stem cell-based treatment would require a robust population of stem cells which can then be treated with the proper compounds to develop into insulin-making pancreatic cells to treat diabetes, or new nerve cells to replace dying ones in Alzheimers, or fresh heart muscle to substitute for scarred tissue after a heart attack.

MORE: Stem Cell Miracle? New Therapies May Cure Chronic Conditions like Alzheimers

Nagys team also described, with the most detail to date, exactly how mature cells like skin cells perform the ultimate molecular feat and become forever young again when exposed to the four genes. They analyzed the changes in the cells DNA, the proteins they made, and more. Its similar to high definition TV, he says. We see things much better with much more detail. We expect that having that high resolution characterization will allow us to better understand what is happening during this process at the molecular level. And obviously that better understanding is going to affect what we can do with these cells to make them better, safer and more efficient in cell-based treatments in the future.

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This New Kind of Stem Cell May Revolutionize How We Treat Diseases

Durham, NC (PRWEB) December 10, 2014

The medical world is excited about the potential that stem cells have demonstrated in aiding the recovery of patients who have suffered a heart attack. Now, a new study appearing in the January issue of STEM CELLS Translational Medicine indicates that stem cells may also benefit those who suffer from hardening of the arteries.

Hardening of the arteries or atherosclerosis occurs due to a buildup of fats, cholesterol and other substances in and on the artery walls. The arteries become hardened by fibrous tissue and calcification and, as the plaque grows, it clogs the artery tubes, reducing the oxygen and blood supply to the affected organ. If the artery becomes severely blocked, it can cause death of the tissue fed by the artery and lead to a heart attack or stroke.

Based on the success of mesenchymal stem cells (MSCs) in treating a heart attack, Shih-Chieh Hung, M.D, Ph.D., of the Department of Medical Research, Taipei Veterans General Hospital, Taiwan, led a team of researchers who wanted to learn if MSCs transplanted in a patient in the early stage of atherosclerosis might prevent the diseases development and/or progression. MSCs are stem cells that can be collected from many adult tissues and differentiate into various cell types, including cartilage, bone, tendons, muscle and skin.

The team began by examining the effects of MSCs on inhibiting atherosclerosis in human/mouse endothelial cells treated with oxidized low-density lipoprotein (oxLDL) in a lab dish. The endothelium is the thin layer of cells that lines the interior surface of blood vessels and lymphatic vessels, forming an interface between circulating blood and the rest of the vessel wall.

Then we moved on to see how they might affect live mice that had been fed a high-fat diet, Dr. Hung said. We found that the MSCs transplantation improved endothelial function and reduced the plaque formation in the lab cells as well as in the high fat-diet fed mice. This leads us to believe that MSCs might prove useful someday in treating atherosclerosis in human patients, he noted.

Dr. Hung said that the next step is to identify ways to maintain the beneficial effect of MSCs for a long time, as well as learn more about the complex mechanism underlying the MSCs transplantation in different stages of atherosclerosis.

This study was aimed at intervening in the early stages of disease development to prevent further progression, said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. It is the first study to show that in animals, stem cells can treat atherosclerosis by repairing the blood vessel lining.

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The article, Mesenchymal Stem Cells Ameliorate Atherosclerotic Lesions Via Restoring Endothelial Function, can be accessed online at http://www.stemcellsTM.com

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Stem Cells Show Promise in Reducing Hardening of the Arteries

CALGARY New research from the University of Calgary may hold the key to restoring hair growth.

The findings, published in the scientific journal Developmental Cell this week, identify the existence of a skin stem cell in adult hair follicles that may one day be targeted to stimulate new hair growth after injury, burns, disease or aging.

The discovery is being called an important a step towards new hair loss treatments.

We hope that we can ultimately stimulate these cells with drugs to replenish or rejuvenate the cells that are responsible for inducing hair growth, says assistant professor in stem cell biology at the Faculty of Veterinary Medicine Jeff Biernaskie, PhD.

Hair follicles undergo a constant cycle of regeneration and degeneration, and Biernaskie wanted to identify the stem cells that oversee that cycle.

Biernaskies team discovered that a small number of dermal sheath cells could self-renew, and gave rise to hundreds of new cells in each hair follicle.

He says the discovery gives researchers a greater understanding of how hair follicles regenerate and it opens the door to creating therapies targeting stem cells to restore hair growth.

However, it could be a decade before such therapies are developed.

Biernaskies research holds hope for animals as well as humans.

Animals suffer skin diseases and injuries similar to people, and he says anything that improves the understanding of stem cells in healing and regeneration in people is also applicable to healing in animals.

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Stem cell discovery could lead to hair loss treatments

Irvine, California (PRWEB) December 08, 2014

The Ageless Derma skin care company has added a moisturizing product to their line that provides continuous hydration to skin throughout the day. The Swiss Apple Stem Cell Oil-Free Continuous Moisturizer uses rare Swiss apple stem cells in combination with other natural substances to aid in skins retention of moisture for a lessening of fine lines and a silky, more comfortable feeling.

The Swiss Apple Stem Cell Oil-Free Continuous Moisturizer contains stem cells from the exotic Malus Domestica, a rare apple from Switzerland known for its long shelf life and its ability to stay fresh without shriveling. This apple species had a flavor that consumers found too acidic, making farmers reluctant to grow it. The Malus Domestica, however, was discovered to have interesting scientific advantages due to its ability to live a long, healthy life without the usual shriveling that accompanies fruit as it ages. The same idea has been transferred to Ageless Dermas latest moisturizer with its incorporation of these stem cell extracts for a renewed and rejuvenated facial complexion. The stem cells help with not only apple longevity, but also with repairing human skin cells. This results in the ultimate reduction of fine lines and wrinkles with regular use.

Other ingredients are added to the Swiss Apple Stem Cell Oil-Free Continuous Moisturizer to make this moisturizer a workhorse of anti-aging and hydrating skin renewal. Ceramides and essential fatty acids account for maximum skin hydration and strengthening of the skin barrier function. Capric Triglycerides silken skin, glycerin keeps moisturization and hydration in balance, and Ceramides 3, 611, and 1 (all lipids) stop moisture from escaping and hold the skin barrier intact. Swiss Apple Stem Cell Oil-Free Continuous Moisturizer also has sodium hyaluronate to attract and keep moisture in. The hyaluronate also aids in blood microcirculation and the smoothing of wrinkles.

The developers at Ageless Derma Skin Care know they are making something extraordinary happen. Their line of physician-grade skin care products incorporates an important philosophy: supporting overall skin health by delivering the most cutting-edge biotechnology and pure, natural ingredients to all of the skin's layers. This attitude continues to resonate to this day with the companys founder, Dr. Farid Mostamand, who nearly ten years ago began his journey to deliver the best skin care alternatives for people who want to have healthy and beautiful looking skin at any age. About this latest Ageless Derma product, Dr. Mostamand says, The Swiss Apple Stem Cell Oil-Free Continuous Moisturizer is a multi-beneficial product that protects skin and works to smooth lines and wrinkles as it keeps moisture in, working throughout the entire day. Without the correct distribution of moisture, skin becomes dry and susceptible to wrinkling. This product is oil-free and can be used for any skin type.

Ageless Derma products are formulated in FDA-approved Labs. All ingredients are inspired by nature and enhanced by science. Ageless Derma products do not contain parabens or any other harsh additives, and they are never tested on animals. The company has developed five unique lines of products to address any skin type or condition.

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Ageless Derma Launches Its Latest Moisturizing Product Featuring Exotic Apple Stem Cells

Software billionaire Paul Allen says he's committing $100 million to create a new institute in Seattle focusing on the mechanics of human cell biology.

The Allen Institute for Cell Science's first project, the Allen Cell Observatory, will focus on creating computational models for the kinds of induced pluripotent stem cells, or IPS cells, that have the ability to turn into heart muscle cells or the epithelial cells that form the inner linings of organs as well as skin.

Such cells hold promise for facilitating research into how cells become diseased, and potentially for growing replacement tissues.

"Cells are the fundamental units of life, with every disease we know of affecting particular types of cells," Allen said in a news release. "Scientists have learned a great deal about many of the 50 trillion cells in our bodies over the last decades, but creating a comprehensive, predictive model of the cell will require a different approach."

The Allen Cell Observatory's goal is to produce a dynamic, visual database and animated models of cell parts in action. Such models could shed light on the processes by which genetic information is translated into cellular functions, and reveal what goes wrong in a diseased cell. That, in turn, could help researchers predict which therapies will work best to counter diseases, or perhaps head off the disease in the first place.

Allen's latest philanthropic venture was unveiled Monday at the American Society for Cell Biology's annual meeting in Philadelphia. It follows up on plans that the co-founder of Microsoft has had in mind for years.

"It's the right time to start a big initiative in cell biology: understanding how cells work, understanding the detailed things that happen inside cells, which is behind cancer and Alzheimer's and all those things," Allen told NBC News last year.

Software billionaire Paul Allen's latest philanthropic project is a $100 million commitment to create the Allen Institute for Cell Science.

Paul Allen's net worth is estimated at more than $17 billion. Over the past 15 years, he has contributed hundreds of millions of dollars to scientific projects including the Allen Telescope Array, the Allen Institute for Brain Science and the Allen Institute for Artificial Intelligence. Last month, he said he would contribute $100 million to the global fight against the Ebola virus. (Allen also owns somewhat less-scientific ventures, such as the Seattle Seahawks and the Portland Trail Blazers.)

The cell science institute will be housed in the seven-story Allen Institute headquarters building that is currently under construction in Seattle's South Lake Union neighborhood. The building is scheduled for completion in the fall of 2015, and will also house the Allen Brain Institute.

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Billionaire Paul Allen Pledges Millions for Cell Science

SEATTLE, Dec. 9 (UPI) -- Microsoft billionaire Paul Allen donated $100 million to study the human cell in an effort to better understand human building blocks and their diseases.

The money will specifically go to the Seattle-based Allen Institute for Cell Science. Their first project will be creating computational models of induced pluripotent stem cells, or IPS cells, that can transform into epithelial cells that form the inner linings of organs as well as skin. This project, called the Allen Cell Observatory, is intended to find how these cells can be diseased and how to possibly form replacement tissue.

"Cells are the fundamental units of life, with every disease we know of affecting particular types of cells," Allen said in a statement. "Scientists have learned a great deal about many of the 50 trillion cells in our bodies over the last decades, but creating a comprehensive, predictive model of the cell will require a different approach."

About 90 percent of cancers are related to epithelial cells. Cancer is caused by a mutation in cells that causes cells to replicate uncontrollably without dying as a healthy cell would. Studying the epithelial cells is potentially a way to see that process in a different light and understand the root cause, thereby putting scientists one step closer to finding a cure.

"If you look at cancer, there are a tremendous number of genes turned on or off or mutated. This is also true for autism. What we don't know is which ones are important and which ones are not. The important ones are the ones that actually change how the cell grows, and once we have a better understanding of how this works we'll have a much better idea of which potential targets for new drugs," said Rick Horwitz, executive director of the institute.

Horwitz said the research and observations of the project will be made publicly available online in an effort to "empower research by our colleagues around the world."

"The cell is so complex, there is no one that I know ... who actually could do this by themselves," he said.

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Paul Allen donates $100 million for research on the human cell

Released: 1-Dec-2014 1:00 PM EST Embargo expired: 3-Dec-2014 5:00 AM EST Source Newsroom: McMaster University Contact Information

Available for logged-in reporters only

Newswise Hamilton, ON (Dec. 3, 2014) Scientists at McMaster University have discovered that human stem cells made from adult donor cells remember where they came from and thats what they prefer to become again.

This means the type of cell obtained from an individual patient to make pluripotent stem cells, determines what can be best done with them. For example, to repair the lung of a patient with lung disease, it is best to start off with a lung cell to make the therapeutic stem cells to treat the disease, or a breast cell for the regeneration of tissue for breast cancer patients.

Pluripotency is the ability stem cells have to turn into any one of the 226 cell types that make up the human body.The work challenges the previously accepted thought that any pluripotent human stem cell could be used to similarly to generate the same amount of mature tissue cells.

This finding, published today in the prestigious science journal Nature Communications, will be used to further drug development at McMaster, and potentially improve transplants using human stem cell sources.

The study was led by Mick Bhatia, director of the McMaster Stem Cell and Cancer Research Institute. He holds the Canada Research Chair in Human Stem Cell Biology and he is a professor in the Department of Biochemistry and Biomedical Sciences of the Michael G. DeGroote School of Medicine.

Its like the stem cell we make wants to become a doctor like its grandpa or an artist like its great-grandma, said Bhatia.

Weve shown that human induced pluripotent stem cells, called iPSCs, have a memory that is engraved at the molecular/genetic level of the cell type used to make them, which increases their ability to differentiate to the parent tissue type after being put in various stem cell states.

So, not all human iPSCs are made equal, Bhatia added. Moving forward, this means that iPSC generation from a specific tissue requiring regeneration is a better approach for future cellular therapies. Besides being faster and more cost-efficient in the development of stem cell therapy treatments, this provides a new opportunity for use of iPSCs in disease modeling and personalized drug discovery that was not appreciated before.

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Not All Induced Pluripotent Stem Cells Are Made Equal

PUBLIC RELEASE DATE:

3-Dec-2014

Contact: Veronica McGuire vmcguir@mcmaster.ca 90-552-591-402-2169 McMaster University @mcmasteru

Hamilton, ON (Dec. 3, 2014) - Scientists at McMaster University have discovered that human stem cells made from adult donor cells "remember" where they came from and that's what they prefer to become again.

This means the type of cell obtained from an individual patient to make pluripotent stem cells, determines what can be best done with them. For example, to repair the lung of a patient with lung disease, it is best to start off with a lung cell to make the therapeutic stem cells to treat the disease, or a breast cell for the regeneration of tissue for breast cancer patients.

Pluripotency is the ability stem cells have to turn into any one of the 226 cell types that make up the human body.The work challenges the previously accepted thought that any pluripotent human stem cell could be used to similarly to generate the same amount of mature tissue cells.

This finding, published today in the prestigious science journal Nature Communications, will be used to further drug development at McMaster, and potentially improve transplants using human stem cell sources.

The study was led by Mick Bhatia, director of the McMaster Stem Cell and Cancer Research Institute. He holds the Canada Research Chair in Human Stem Cell Biology and he is a professor in the Department of Biochemistry and Biomedical Sciences of the Michael G. DeGroote School of Medicine.

"It's like the stem cell we make wants to become a doctor like its grandpa or an artist like its great-grandma," said Bhatia.

"We've shown that human induced pluripotent stem cells, called iPSCs, have a memory that is engraved at the molecular/genetic level of the cell type used to make them, which increases their ability to differentiate to the parent tissue type after being put in various stem cell states.

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Not all induced pluripotent stem cells are made equal: McMaster researchers

NEWS

1200+ scientists, patient advocates from 40 countries in town for summit

Posted TODAY, 6:04 PM Updated TODAY, 6:33 PM

SAN ANTONIO - More than a thousand scientists, industry leaders and patient advocates from 40 countries are headed to San Antonio for the World Stem Cell Summit.

Organizers are calling it the center of the universe when it comes to stem cells and regenerative medicine.

On Tuesday the summit kicked off with Public Education Day, where some of the smartest scientists in the field broke the topic down into bite-sized pieces.

"To be able to replenish our cells that die within a tissue on a daily basis, in order for us to be able to heal wounds, we have to have stem cells," said Elaine Fuchs, an investigator for the Howard Hughes Medical Institute.

She started her research in the field in the 1970s with work on skin stem cells, and said she was fascinated with creating skin in a petri dish that could then be used for burn therapy.

Fuchs spoke at Public Education Day about the most basic biology of stem cells and said that knowledge is leading to a new world in medicine.

"The biology of stem cells is gong to be and is being extremely valuable in terms of developing new therapies and coming up with new drugs to treat various different devastating diseases," Fuchs said.

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World Stem Cell Summit kicks off in SA with Public Education Day

This active ingredient won the prize in European Innovation Best Active Ingredient in 2008. It is a revolutionary technology designed to protect human skin stem cells with the help of stem cells from a rare Swiss apple. The clinical trials conducted by the company who discovered this ingredient showed that 100% of the participants saw a reduction in fine lines and wrinkles after using a solution containing 2% PhytoCellTech Malus Domestica.

According to the Bible, Adam bit into an apple (coaxed on by us femme fatales) and deprived Earth of Heaven...was he attracted by the delicious taste or did he already know of the amazing youth-boosting properties of this fruit?

PhytoCellTec Malus Domestica is an award-winning patented liposomal preparation, so containing tiny bubbles made out of the same material as cell membranes, based on the stem cells of a rare Swiss apple called Uttwiler Sptlauber that derives from a seedling planted in the middle of the18th century. Uttwiler Sptlauber is an endangered apple variety that is well-known for its ability to be stored for long periods without shrivelling and thus its longevity potential. The apples are rich in phytonutrients, proteins and long-living cells. A novel technology has now been developed enabling the cultivation of rare and endangered species like Uttwiler Sptlauber. Thanks to this technology, plant stem cells can be obtained and incorporated into skin care products to enhance the longevity of skin cells. Not only does it protect the skins own stem cells but has been shown to have excellent age-delaying and anti-wrinkle properties, and is currently one of the most pioneering and exciting ingredients in skin care.

Stem Cells and Longevity

Longevity is related to specific cells called stem cells which have a unique growth characteristic. These cells can make identical copies of themselves as well as differentiate (in other words, split) to become separate, specialised cells. Two basic types of stem cells are present in the human body:

Embryonic stem cells found in blastocysts (structures found in the human pre-embryonic stage) can grow and differentiate into one of the more than 220 different cell types which make up the human body;

Adult stem cells located in some adult tissues can only differentiate into their own or related cell types. These cells act as a repair system for the body but also maintain the normal turnover of regenerative organs such as blood, skin or intestinal tissues.

Research on Stem Cells and Applications

Currently in medicine, adult stem cells are already used particularly in transplant medicine to treat leukemia and severe burns. In the cosmetic field, scientists are focusing their research on adult stem cells located in the skin. They are studying the potential of this type of cells, their functioning and aging. This research is helping us understand how to protect skin stem cells.

Stem Cells in the Human Skin

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Swiss Apple Stem Cells for perfect skin. What do plant ...

New research has found evidence that stem cells could be used to correct genetic defects in skin and to treat certain rare diseases.

Three separate studies by scientists in the US, Europe and Japan have raised hopes that the methods could be used to develop treatments for a range of problems, including epidermolysis bullosa.

It is a disorder wheresufferers are born with extensive blistering and patches of missing skin.

They areleft with extremely fragile skin for all of their lives.

In the first study, the researchers used Induced Pluripotent Stem Cells (iPSCs) - adult cells that are reprogrammed to an embryonic stem cell-like state.

The scientists took diseased cells from three adult patients withepidermolysis bullosa.

The researchers converted the cells into iPSCs and used specialist tools to edit and fix the mutation in the genetic code responsible for defective collagen protein production, which causes the condition.

They then grew pieces of human skin that produced the correct collagen, and grafted them into mice where they lasted for three weeks.

It i's hoped the risk of rejection in humans will be minimal because the skin is made from the patient's own cells.

A second study confirmed these findings in the lab, showing that it is possible to genetically correct iPSCs from mice with epidermolysis bullosa and use the repaired cells to heal blistered skin.

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Scientists use stem cells to correct skin defects

Irvine, California (PRWEB) November 27, 2014

The Ageless Derma skin care company has just released their latest development in the form of a facial mask that exfoliates skin with ingredients such as apple stem cells to renew the complexion and correct texture and tone. The companys Swiss Apple Stem Cell Mask incorporates the cells of a long-living rare apple with other revitalizing ingredients from nature to result in a gentle mask that is effective and calming.

The Swiss apple, Malus Domestica, has its beginnings that go as far back as 18th century Switzerland. Ageless Derma recognized the importance of this plants stem cell extract for its ability to keep the fruit fresh for extended periods of time without wrinkling or shriveling. The Swiss Apple Stem Cell Mask contains the scientific advances that come from the cultivation of these stem cells, having incorporated it into a powerful and effective facial mask to rejuvenate skin and keep wrinkles at bay.

The Swiss Apple Stem Cell Mask contains other natural ingredients that work together to keep skin at its purest and return youthful life to the complexion. Kaolin Clay from the earth absorbs toxins that can enter the skins surface due to environmental pollutants in the air. The clay helps draw out grime and purify skin. Sweet Almond Oil nourishes skin, and adds much needed moisture and smoothness. Safflower Oil improves the texture of skin; especially skin that has become roughened with time and sun exposure. The Safflower Oil in Swiss Apple Stem Cell Mask also locks in moisture and tones skin for a flawless and radiant complexion.

Ageless Derma added fruit extracts to the Swiss Apple Stem Cell Mask for added health and radiance. Pumpkin Fruit Ferment, Pineapple Enzyme, and Papaya Enzyme make this mask luscious and plush. Age-defying antioxidants are also included, with Green Tea Extract and Aloe Leaf Extract added for soothing and fighting free radicals.

The developers at Ageless Derma Skin Care know they are making something extraordinary happen. Their line of physician-grade skin care items incorporates an important philosophy: promoting overall skin health by delivering the most cutting-edge biotechnology and pure, natural ingredients to all of the skin's layers. This attitude continues to resonate to this day with the companys founder, Dr. Farid Mostamand, who nearly a decade ago began his journey to deliver the best skin care alternatives for people who want to have healthy and beautiful looking skin at any age. About this latest Ageless Derma product, Dr. Mostamand says, This natural enzymatic Swiss Apple Stem Cell Mask gently exfoliates dead skin cells that are blocking new cell turnover for a renewed and radiant complexion. This is accomplished without the use of unnatural chemicals that can harm your skins delicate balance.

Ageless Derma products are formulated in FDA-approved Labs. All ingredients are inspired by nature and enhanced by science. Ageless Derma products do not contain parabens or any other harsh additives, and they are never tested on animals. The company has developed five unique lines of products to address any skin type or condition.

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Ageless Derma Introduces Their Latest Innovation: Swiss Apple Stem Cell Mask

27.11.2014 - (idw) IMBA - Institut fr Molekulare Biotechnologie der sterreichischen Akademie der Wissenschaften GmbH

Scientists at IMBA Institute of Molecular Biotechnology of the Austrian Academy of Sciences in Vienna have made a major advancement towards a future therapy for butterfly children. A treatment with fibroblasts generated from induced pluripotent stem cells has been highly successful in mice. The next step is to establish this method in humans. Butterfly children suffer from Epidermolysis Bullosa (EB), a debilitating skin disease. It is caused by a genetic defect that leads to a deficiency or complete lack of various structural proteins. In one particularly severe form, the protein collagen 7 is either missing or present only in insufficient amounts. If that bond is missing, the skin forms blisters or tears at the slightest mechanical pressure, leading to wounds and inflammation that require extensive treatment with creams and bandages. Often these constant lesions also lead to aggressive forms of skin cancer.

Presently there is no cure for this disease. But there are promising approaches that could lead to successful treatments in the future. One of them is a method called fibroblast injection. In this procedure, fibroblasts are injected between the layers of the skin, where they can produce the necessary collagen 7.

Researchers at IMBA under the leadership of Arabella Meixner have now been successful in developing this method to treat mice affected by EB. The individual steps of this treatment have been worked out and carefully tested in many years of laboratory work, and the results have now been published in the scientific journal Science Translational Medicine.

First the scientists returned skin cells of the diseased mice to the stem cell stage and then repaired the genetic defect, the root cause of the disease. Then the researchers transformed stem cells back into fibroblasts.

Before the repaired fibroblasts could be reintroduced into the organism, measures to prevent inflammation or rejection were necessary. In this study the researchers conducted a type of toxicity test, and the results were very promising. After several months of observation, no adverse immune reactions occurred, and the risk of skin cancer did not increase. That is an important consideration because butterfly children already have a greatly increased risk of skin cancer.

The next step is to establish this skin stem cell treatment in humans. To achieve that, the IMBA scientists intend to look for partners with clinical experience. For severe forms of Epidermolysis Bullosa, a systemic application needs to be developed to spread the cells throughout the entire body via the bloodstream to reach epithelial tissues that are more difficult to access, for example the mucous membranes in the mouth or bowels. Often in butterfly children with milder forms of the disease, only certain areas of the skin are affected. The skin stem cell therapy with local injections successfully tested on mice could lead to a valuable treatment method in the very near future.

The project conducted by IMBA scientists was initiated by the patient organization DEBRA Austria, and has had the financial support of the association and of other generous supporters since 2009. DEBRA's mission is to ensure that butterfly children receive competent specialized medical care and to promote research into options to relieve and cure EB. Further thanks also go to our funding and cooperation partners sterreichische Lotterien and FK Austria Wien.

Original publication: Wenzel et. al., iPSC-based cell therapy for Recessive Dystrophic Epidermolysis Bullosa. Science Translational Medicine. 2014.

Scientific Contact: Dr. Arabella Meixner, Research Lead Tel. +43 664 2018084 arabella.meixner@imba.oeaw.ac.at Weitere Informationen:http://www.imba.oeaw.ac.at

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Tremendous progress in the development of skin stem cell treatments for butterfly children

A team led by scientists from The Scripps Research Institute (TSRI) has found a simple method to convert human skin cells into the specialized neurons that detect pain, itch, touch and other bodily sensations. These neurons are also affected by spinal cord injury and involved in Friedreich's ataxia, a devastating and currently incurable neurodegenerative disease that largely strikes children.

The discovery allows this broad class of human neurons and their sensory mechanisms to be studied relatively easily in the laboratory. The "induced sensory neurons" generated by this method should also be useful in the testing of potential new therapies for pain, itch and related conditions.

"Following on the work of TSRI Professor Ardem Patapoutian, who has identified many of the genes that endow these neurons with selective responses to temperature, pain and pressure, we have found a way to produce induced sensory neurons from humans where these genes can be expressed in their 'normal' cellular environment," said Associate Professor Kristin K. Baldwin, an investigator in TSRI's Dorris Neuroscience Center. "This method is rapid, robust and scalable. Therefore we hope that these induced sensory neurons will allow our group and others to identify new compounds that block pain and itch and to better understand and treat neurodegenerative disease and spinal cord injury."

The report by Baldwin's team appears as an advance online publication in Nature Neuroscience on November 24, 2014.

In Search of a Better Model

The neurons that can be made with the new technique normally reside in clusters called dorsal root ganglia (DRG) along the outer spine. DRG sensory neurons extend their nerve fibers into the skin, muscle and joints all over the body, where they variously detect gentle touch, painful touch, heat, cold, wounds and inflammation, itch-inducing substances, chemical irritants, vibrations, the fullness of the bladder and colon, and even information about how the body and its limbs are positioned. Recently these neurons have also been linked to aging and to autoimmune disease.

Because of the difficulties involved in harvesting and culturing adult human neurons, most research on DRG neurons has been done in mice. But mice are of limited use in understanding the human version of this broad "somatosensory" system.

"Mouse models don't represent the full diversity of the human response," said Joel W. Blanchard, a PhD candidate in the Baldwin laboratory who was co-lead author of the study with Research Associate Kevin T. Eade.

A New Identity

For the new study, the team used a cell-reprogramming technique (similar to those used to reprogram skin cells into stem cells) to generate human DRG-type sensory neurons from ordinary skin cells called fibroblasts.

Excerpt from:
Pain and itch in a dish: Scientists convert human skin cells into sensory neurons

Previous studieshaveunsuccessfullytried to producenerve cells from embryonic stem cells For the recent study, a team of USresearchers used adult tissue instead They were able to reprogram ordinary skin cells into induced stem cells Scientistsat Harvard Medical School in Massachusetts used a cocktail of proteins called transcription factors that control the activity of genes Study could help reveal the origins of pain and develop better drugs

By Sarah Griffiths for MailOnline

Published: 13:04 EST, 24 November 2014 | Updated: 13:16 EST, 24 November 2014

Pain is a complex and unpleasant sensation, which some people feel more acutely than others - and its origins remain largely a mystery.

Now, scientists have created pain in a dish by converting skin cells into sensitive neurons in a bid to learn more about these sensations.

The lab-created nerve cells respond to a range of different kinds of pain stimulation, including physical injury, chronic inflammation and cancer chemotherapy.

Scientists have created pain in a dish by converting skin cells into sensitive neurons (illustrated) in a bid to learn more about its origins.In the future, the research could be used to develop better pain-relieving drugs

And in the future, the custom-made neurons could be used to investigate the origins of pain and develop better pain-relieving drugs.

The work follows years of unsuccessful attempts to produce nerve cells from embryonic stem cells, which are immature blank slate cells with the potential to become any tissue in the body.

A nociceptor is a receptor of a nerve cell that responds to potentially damaging stimuli by sending signals to the spinal cord and brain.

See the article here:
Nerve cells 'grown' in a lab could reveal more about how injury affects the body

London: Scientists have created "pain in a dish" by converting skin cells into sensitive neurons.

The laboratory-generated nerve cells respond to a range of different kinds of pain stimulation, including physical injury, chronic inflammation and cancer chemotherapy.

In future they could be used to investigate the origins of pain and develop better pain-relieving drugs.

The work followed years of unsuccessful attempts to produce nerve cells from embryonic stem cells, immature "blank slate" cells with the potential to become any tissue in the body.

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A turning point came with the development of technology that allowed ordinary skin cells to be reprogrammed into "induced" stem cells.

A team led by Dr Clifford Woolf at Harvard Medical School used a cocktail of "transcription factors" - proteins that control the activity of genes - to transform mouse and human skin cells directly into pain-sensing neurons.

The researchers, whose findings are reported in the journal Nature Neuroscience, were able to model pain hypersensitivity experienced by patients who donated skin cells to the study.

Dr Woolf said: "I think the ability to make human pain neurons for the pain field is going to be very important. Furthermore, our failure with embryonic stem cells led us to work with adult tissue samples, making the technology much more clinically relevant since these are easy to collect from patients suffering from different kinds of pain."

The researchers produced "nociceptors", sensory nerve endings that respond to potentially damaging stimuli by sending pain signals to the spinal cord and brain.

Original post:
Scientists create 'pain in a dish'

Young guys in large vehicles most likely to survive crash Young guys in large vehicles most likely to survive crash

Driving a large vehicle and being a young male are among the factors that improve a person's chances of surviving a car crash, a new study finds.

Driving a large vehicle and being a young male are among the factors that improve a person's chances of surviving a car crash, a new study finds.

Jogging helps seniors maintain their ability to walk, a new study finds.

Jogging helps seniors maintain their ability to walk, a new study finds.

Researchers have discovered the stem cells that allow your nails to grow back after you lose them.

Researchers have discovered the stem cells that allow your nails to grow back after you lose them.

The holidays can be a challenge for families of children with autism because sensory overload can trigger major meltdowns, an expert says.

The holidays can be a challenge for families of children with autism because sensory overload can trigger major meltdowns, an expert says.

A brain abnormality may be responsible for more than 40 percent of deaths from sudden infant death syndrome (SIDS), a new study suggests.

See original here:
Researchers find stem cells that help nails regenerate

Scientists have created pain in a dish by converting skin cells into sensitive neurons.

The laboratory-generated nerve cells respond to a range of different kinds of pain stimulation, including physical injury, chronic inflammation, and cancer chemotherapy.

In future they could be used to investigate the origins of pain and develop better pain-relieving drugs.

The work followed years of unsuccessful attempts to produce nerve cells from embryonic stem cells, immature blank slate cells with the potential to become any tissue in the body.

A turning point came with the development of technology that allowed ordinary skin cells to be re-programmed into induced stem cells.

A team led by Dr Clifford Woolf at Harvard Medical School used a cocktail of transcription factors proteins that control the activity of genes to transform mouse and human skin cells directly into pain-sensing neurons.

The researchers, whose findings are reported in the journal Nature Neuroscience, were able to model pain hypersensitivity experienced by patients who donated skin cells to the study.

Read the original post:
Scientists have created 'pain in a dish'

Researchers found stem cells in mouse nails that performed two roles They cause nails to grow, and focus on repair when it is lost or injured The experts tracked how stem cells in the nails of mice split and grow It is hoped the same cells could be manipulated to grow tissue in other body parts

By Ellie Zolfagharifard for MailOnline

Published: 10:23 EST, 24 November 2014 | Updated: 10:23 EST, 24 November 2014

The blue-tailed skink has the remarkable ability to lose its tail to distract predators, and then grow a new one.

And someday, thanks to cells found in our nails, humans could have similar lizard-like abilities that will help us regrow lost limbs.

Researchers in the US recently found unique stem cells in nails that perform two roles - they cause nails to grow, and they focus on nail repair when it is lost or injured.

Researchers in the US recently found unique stem cells (shown in the above animation) in nails that perform two roles; they cause nails to grow, and focus on nail repair when it is lost or injured

The researchers claim these stem cells could be manipulated to grow tissue for other body parts, helping to someday recover lost limbs or organs.

The elusive stem cells were found at the University of Southern California by attaching dyes as 'labels' on mouse nail cells.

Many of these cells repeatedly divided, diluting the dyes and labels in the process.

Originally posted here:
Could nails help us regrow LIMBS? Stem cells found on fingers and toes could someday give humans lizard-like abilities

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Newswise LA JOLLA, CANovember 24, 2014A team led by scientists from The Scripps Research Institute (TSRI) has found a simple method to convert human skin cells into the specialized neurons that detect pain, itch, touch and other bodily sensations. These neurons are also affected by spinal cord injury and involved in Friedreichs ataxia, a devastating and currently incurable neurodegenerative disease that largely strikes children.

The discovery allows this broad class of human neurons and their sensory mechanisms to be studied relatively easily in the laboratory. The induced sensory neurons generated by this method should also be useful in the testing of potential new therapies for pain, itch and related conditions.

Following on the work of TSRI Professor Ardem Patapoutian, who has identified many of the genes that endow these neurons with selective responses to temperature, pain and pressure, we have found a way to produce induced sensory neurons from humans where these genes can be expressed in their normal cellular environment, said Associate Professor Kristin K. Baldwin, an investigator in TSRIs Dorris Neuroscience Center. This method is rapid, robust and scalable. Therefore we hope that these induced sensory neurons will allow our group and others to identify new compounds that block pain and itch and to better understand and treat neurodegenerative disease and spinal cord injury.

The report by Baldwins team appears as an advance online publication in Nature Neuroscience on November 24, 2014.

In Search of a Better Model

The neurons that can be made with the new technique normally reside in clusters called dorsal root ganglia (DRG) along the outer spine. DRG sensory neurons extend their nerve fibers into the skin, muscle and joints all over the body, where they variously detect gentle touch, painful touch, heat, cold, wounds and inflammation, itch-inducing substances, chemical irritants, vibrations, the fullness of the bladder and colon, and even information about how the body and its limbs are positioned. Recently these neurons have also been linked to aging and to autoimmune disease.

Because of the difficulties involved in harvesting and culturing adult human neurons, most research on DRG neurons has been done in mice. But mice are of limited use in understanding the human version of this broad somatosensory system.

Mouse models dont represent the full diversity of the human response, said Joel W. Blanchard, a PhD candidate in the Baldwin laboratory who was co-lead author of the study with Research Associate Kevin T. Eade.

See more here:
Pain and Itch in a Dish

November 25, 2014

Chuck Bednar for redOrbit.com Your Universe Online

Two different teams of researchers, one led by scientists from The Scripps Research Institute (TSRI) and the other involving members of the Harvard Stem Cell Institute (HSCI) have discovered ways to create the neurons that detect pain, itch and other sensations in laboratory conditions out of human and mouse skin cells.

The TSRI study, which was published online Monday in the journal Nature Neuroscience, used what the authors referred to as a simple technique to create neurons that normally reside in clusters called dorsal root ganglia (DRG) along the outer spine. Those neurons are often affected by spinal cord injuries and a neurodegenerative condition known as Friedreichs ataxia.

According to the researchers, DRG sensory neurons extend their nerve fibers into skin, muscle and joints located throughout the body. The neurons are capable of alternately detecting gentle touch, painful contact, heat, cold, wounds, inflammation, chemical irritants, itch-inducing agents and fullness of the bowels and bladder. They also relay information about the position of the body and limbs, and have been linked to aging and autoimmune disease.

Due to the difficulties involved in culturing adult human neurons, most research relating to DRG neurons has been done in mice. However, the rodents are of limited use in understanding the human version of this somatosensory system, TSRI explained. The new discovery will allow this type of human neurons and their associated sensory mechanisms to be studied with relative ease in laboratory conditions, according to the study authors.

We have found a way to produce induced sensory neurons from humans where these genes can be expressed in their normal cellular environment, associate professor Kristin K. Baldwin, an investigator in TSRIs Dorris Neuroscience Center, said in a statement. This method is rapid, robust and scalable. Therefore we hope that these induced sensory neurons will allow our group and others to identify new compounds that block pain and itch and to better understand and treat neurodegenerative disease and spinal cord injury.

Similarly, the HSCI-led study, which included experts from Boston Childrens Hospital (BCH) and Harvards Department of Stem Cell and Regenerative Biology (HSCRB), was able to successfully convert mouse and human skin cells into pain-sensing neurons that responded to several different types of stimuli responsible for causing both acute and inflammatory pain.

The authors of this study, which also appeared in Wednesdays online edition of Nature Neuroscience, said that their research could help scientists better understand the different types of pain that we experience, as well as better identify why people respond to pain in different ways and why some individuals are more or less likely to develop chronic pain. It could also result in the development of improved pain-relieving medications.

The six-year project resulted in the creation of neuronal pain receptors that respond to both the types of intense stimuli triggered by a physical injury, and the more subtle stimuli triggered by inflammation which results in pain tenderness. The researchers report that the fact the neurons can respond to both the gross and fine forms of stimulation which produce separate types of pain in humans confirm that they are functionally normal.

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Pain-Sensing Neurons Created From Human, Mouse Skin Cells

1. Keratinocytes

There are two approaches to commit ES cells and adult stem cells (of non-epidermal origin) to the keratinocyte lineage in vitro. One approach would be to expose the cells to a cocktail of exogenous cytokines, growth factors, chemicals, and extracellular matrix (ECM) substrata over a prolonged duration of in vitro culture. Only a fraction of the stem cells would be expected to undergo commitment to the keratinocyte lineage, because many of these cytokines, growth factors, chemicals, and ECM substrata would exert non-specific pleitropic effects on stem cell differentiation into multiple lineages. At best, the cocktail combination of various cytokines, growth factors, chemicals, and ECM substrata can be optimized by trial and error, to maximize the proportion of stem cells committing to the keratinocyte lineage, while at the same time yielding a large number of other undesired lineages. Hence, extensive selection/purification and proliferation of the commited keratinocyte progenitors is likely to be required.

By using such an approach, Coraux et al.54 managed to achieve commitment and subsequent differentiation of murine ES cells into the keratinocyte lineage, in the presence of a cocktail combination of bone morphogenetic protein-4 (BMP-4), ascorbate, and ECM derived from human normal fibroblasts (HNFs) and murine NIH-3T3 fibroblasts. Nevertheless, it must be noted that the study of Coraux et al.54 also reported a high degree (approximately 80%) of non-specific differentiation into multiple uncharacterized lineages, and no attempt was made to purify differentiated keratinocytes or keratinocyte progenitors from the mixture of lineages derived from murine ES cells. Bagutti et al.61 reported that coculture with human dermal fibroblasts (HDFs) as well as HDF-conditioned media could induce beta integrin- deficient murine ES cells to commit and differentiate into the keratinocyte lineage. However, as with the study of Coraux et al.,54 the keratinocytes were interspersed with differentiated cells of other lineages. Recently, differentiation of human ES cells into the keratinocyte lineage was also reported by Green et al.62 However, this study was based on in vivo teratoma formation within a SCID mouse model, and to date, there are no parallel in vitro studies that have been reported.

With adult stem cells of non-epidermal origin, there are also few studies 63, 64 which have successfully achieved re-commitment and trans-differentiation to the keratinocyte lineage. Even so, these studies were based primarily on the transplantation of undifferentiated stem cells in vivo, with the observed trans-differentiation occurring sporadically and at extremely low frequencies. Moreover, the validity of the experimental data may be clouded by controversy over the artifact of stem cell fusion in vivo.65 To date, there are no parallel in vitro studies that have achieved recommitment and trans-differentiation of non-epidermal adult stem cells to the keratinocyte lineage. It can therefore be surmised that the use of exogenous cytokines, growth factors, chemicals, and ECM substrata to induce ES cell and nonepidermal adult stem cell commitment to the keratinocyte lineage is a relatively inefficient, time-consuming, and labor-intensive process that would require extensive selection and purification of the committed keratinocyte progenitors. Hence, it would be technically challenging to apply this to the clinical situation.

The other approach for inducing ES cell and non-epidermal adult stem cell commitment to the keratinocyte lineage is through genetic modulation. This may be achieved by transfecting stem cells with recombinant DNA constructs encoding for the expression of signaling proteins that promote commitment to the keratinocyte lineage. Of particular interest are the Lef-1/Tcf family of Wnt regulated transcription factors that act in concert with b-catenin,66, 67 c-myc which is a downstream target of the Wnt-signaling pathway,68, 69 and the transactivation domain containing isoform of transcription factor p63 (Tap63).70, 71 Interestingly, the transcription factor GATA-3, which is well known to be a key regulator of T-cell lineage determination, has also been shown to be essential for stem cell lineage determination in skin, where it is expressed at the onset of epidermal stratification and Inner Root Sheath (IRS) specification in follicles.72 Recombinant overexpression of p6373 and c-Myc74 has been reported to promote commitment and differentiation to the keratinocyte lineage.

The disadvantage of directing differentiation through genetic modulation is the potential risks associated with utilizing recombinant DNA technology in human clinical therapy. For example, the overexpression of any one particular protein within transfected stem cells would certainly have unpredictable physiological effects upon transplantation in vivo. This problem may be overcome by placing the recombinant expression of the particular protein under the control of switchable promoters, several of which have been developed for expression in eukaryotic systems. Such switchable promoters could be responsive to exogenous chemicals,75 heat shock,76 or even light.77 Genetically modified stem cells may also run the risk of becoming malignant within the transplanted recipient. Moreover, there are overriding safety concerns with regard to the use of recombinant viral based vectors in the genetic manipulation of stem cells.78 It remains uncertain as to whether legislation would ultimately permit the use of genetically modified stem cells for human clinical therapy. At present, the potential detrimental effects of transplanting genetically modified stem cells in vivo are not well studied. More research needs to be carried out on animal models to address the safety aspects of such an approach.

More recently, there is emerging evidence that some transcription factors (which are commonly thought of as cytosolic proteins) have the ability to function as paracrine cell to cell signaling molecules.79 This is based on intercellular transfer of transcription factors through atypical secretion and internalization pathways.79 Hence, there is an exciting possibility that transcription factors implicated in commitment to the keratinocyte lineage may in the future be genetically engineered to incorporate domains that enable them to participate in novel paracrine signaling mechanisms. This in turn would have tremendous potential for inducing the commitment of ES cells and non-epidermal adult stem cells to the keratinocyte lineage.

Skin appendages, including hair follicles, sebaceous glands and sweat glands, are linked to the epidermis but project deep into the dermal layer. The skin epidermis and its appendages provide a protective barrier that is impermeable to harmful microbes and also prevents dehydration. To perform their functions while being confronted with the physicochemical traumas of the environment, these tissues undergo continual rejuvenation through homeostasis, and, in addition, they must be primed to undergo wound repair in response to injury. The skins elixir for maintaining tissue homeostasis, regenerating hair, and repairing the epidermis after injury is its stem cells.

The hair follicle is composed of an outer root sheath that is contiguous with the epidermis, an inner root sheath and the hair shaft. The matrix surrounding the dermal papilla, in the hair root, contains actively dividing, relatively undifferentiated cells and is therefore a pocket of MSCs that are essential for follicle formation. The lower segment of each hair follicle cycles through periods of active growth (anagen), destruction (catagen) and quiescence (telogen).80 A specialized region of the outer root sheath of the hair follicle, known as the bulge, is located below the sebaceous gland, which is also the attachment site of the arrector pili muscle, receiving inputs from sensory nerve endings and blood vessels. Furthermore, the hair follicle bulge is a reservoir of slow-cycling multipotent stem cells.81, 82 Subsets of these follicle-derived multipotent stem cells can be activated and migrate out of hair follicles to the site of a wound to repair the damaged epithelium; however, they contribute little to the intact epidermis. These hair follicle stem cells can also contribute to the growth of follicles themselves and the sebaceous gland. For example, in the absence of hair follicle stem cells, hair follicle and sebaceous gland morphogenesis is blocked, and epidermal wound repair is compromised.83 In addition to containing follicle epidermal stem cells, the bulge contains melanocyte stem cells.84 Recent studies show that nestin, a marker for neural progenitor cells, is selectively expressed in cells of the hair follicle bulge and that these stem cells can differentiate into neurons,85 glia, keratinocytes, smooth muscle cells, melanocytes and even blood vessels.86, 87 Examination of close developmental and anatomical parallels between epithelial tissue and dermal tissue in skin and hair follicles has revealed dermal tissue to have stem cells. Paus et al. indicated that hair follicle dermal sheath cells might represent a source of dermal stem cells that not only incorporate into the hair-supporting papilla, low down in the follicle, but also move up and out from the follicle dermal sheath into the dermis of adjoining skin.88 Hair follicle dermal sheath cells taken from the human scalp can form new dermal papilla, induce the formation of hair follicles, and produce hair shafts when transplanted onto skin.89 There is also a clear transition from dermal sheath to dermal papilla cells.90 When the follicle dermal cells are implanted into skin wounds, they can be incorporated into the new dermis in a manner similar to that of skin wound-healing fibroblasts.91 However, these cell populations still lack specific markers for purifying and distinguishing the stem cells from their progeny. Furthermore, of prime importance is improving our understanding of the relation between bulge cells and interfollicular epidermal stem cells and between bulge cells and other stem cells inhabiting the skin and the mechanisms of hair growth.

Recently, cell replacement therapy has offered a novel and powerful medical technology for skin repair and regeneration: a new population of stem cell, called a neural crest stem cell, from adult hair follicles, was discovered to have the ability to differentiate in vitro to keratinocytes, neurons, cartilage/bone cells, smooth muscle cells, melanocytes, glial cells, and adipocytes.9296 In mammalian skin, skin-derived neural progenitors were isolated and expanded from the dermis of rodent skin and adult human scalp and could differentiate into both neural and mesodermal progeny.97, 98 Skin-derived neural progenitor cells were isolated based on the sphere formation of floating cells after 37 days of culture in uncoated flasks with epidermal growth factor and fibroblast growth factor, and characterized by the production of nestin and fibronectin, markers of neural precursors. In addition, skin-derived neural progenitor cells were identified as neural crest derived by the use of Wnt1 promoter driving LacZ expression in the mouse. Some of the LacZ-positive cells were found in the skin of the face, as well as in the dermis and dermal papilla of murine whisker.99 These skin derived neural crest cells have already shown promising results in regenerative medicine such as the promotion of regenerative axonal growth after transplantation into injured adult mouse sciatic nerves 95 or spinal cord repair,100 resulting in the recovery of peripheral nerve function. This new study marks an important first step in the development of real stem-cell-based therapies and skin tissue regeneration.

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Stem Cells for Skin Tissue Engineering and Wound Healing