January 28, 2014

Brett Smith for redOrbit.com Your Universe Online

While a Chinese cream may not have cured George Costanzas baldness in a classic Seinfeld episode, stem cell research from scientists at the University of Pennsylvania has shown the potential for regenerating hair follicles which could lead to relief for hair-challenged men everywhere.

According to a new report published in the journal Nature Communications, the Pennsylvania researchers have developed a groundbreaking method for converting adult cells into epithelial stem cells (EpSCs). Similar previous efforts have failed to generate an adequate number of hair-follicle-generating stem cells.

In the study, epithelial stem cells were inserted into immunocompromised mice. The stem cells regenerated the various cell types for human skin and hair follicles, and provided structurally identifiable hair shafts, raising the possibility of hair regeneration in humans.

The study team began with human skin cells referred to as dermal fibroblasts. By incorporating three genes, they modified those cells into induced pluripotent stem cells (iPSCs), which have the capacity to differentiate into any cell types in the human body. Next, they modified the iPS cells into epithelial stem cells, commonly located at the base of hair follicles.

Starting with procedures other research groups had worked out to transfer iPSCs into skin cells, Xus team figured out that by carefully manipulating the timing of the cell growth factors, they could drive the iPSCs to produce large quantities of epithelial stem cells. This method was able to turn more than 25 percent of the iPSCs into epithelial stem cells within 18 days. Those cells were then purified based on the proteins they showed on their surfaces.

Comparison of the engineered cells with epithelial stem tissue obtained from hair follicles revealed the team succeeded in making the cells they set out to produce. After mixing all those cells with mouse follicular inductive dermal cells and attaching them onto the pores and skin of immunodeficient mice, the team was able to produce efficient outer layers of human skin tissue and follicles structurally similar to those generated by human hair.

This is the first time anyone has made scalable amounts of epithelial stem cells that are capable of generating the epithelial component of hair follicles, said study author Dr. Xiaowei George Xu, associate professor of pathology and laboratory medicine and dermatology at the university. He added that these cells could be used for healing, cosmetics and hair regeneration.

Xu cautioned that iPSC-derived epithelial stem cells are not yet ready for human subjects.

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Are Stem Cells The Cure To Baldness?

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Newswise PHILADELPHIA - If the content of many a situation comedy, not to mention late-night TV advertisements, is to be believed, theres an epidemic of balding men, and an intense desire to fix their follicular deficiencies.

One potential approach to reversing hair loss uses stem cells to regenerate the missing or dying hair follicles. But it hasnt been possible to generate sufficient number of hair-follicle-generating stem cells until now.

Xiaowei George Xu, MD, PhD, associate professor of Pathology and Laboratory Medicine and Dermatology at the Perelman School of Medicine, University of Pennsylvania, and colleagues published in Nature Communications a method for converting adult cells into epithelial stem cells (EpSCs), the first time anyone has achieved this in either humans or mice.

The epithelial stem cells, when implanted into immunocompromised mice, regenerated the different cell types of human skin and hair follicles, and even produced structurally recognizable hair shaft, raising the possibility that they may eventually enable hair regeneration in people.

Xu and his team, which includes researchers from Penns departments of Dermatology and Biology, as well as the New Jersey Institute of Technology, started with human skin cells called dermal fibroblasts. By adding three genes, they converted those cells into induced pluripotent stem cells (iPSCs), which have the capability to differentiate into any cell types in the body. They then converted the iPS cells into epithelial stem cells, normally found at the bulge of hair follicles.

Starting with procedures other research teams had previously worked out to convert iPSCs into keratinocytes, Xus team demonstrated that by carefully controlling the timing of the growth factors the cells received, they could force the iPSCs to generate large numbers of epithelial stem cells. In the Xu study, the teams protocol succeeded in turning over 25% of the iPSCs into epithelial stem cells in 18 days. Those cells were then purified using the proteins they expressed on their surfaces.

Comparison of the gene expression patterns of the human iPSC-derived epithelial stem cells with epithelial stem cells obtained from human hair follicles showed that the team had succeeded in producing the cells they set out to make in the first place. When they mixed those cells with mouse follicular inductive dermal cells and grafted them onto the skin of immunodeficient mice, they produced functional human epidermis (the outermost layers of skin cells) and follicles structurally similar to human hair follicles.

This is the first time anyone has made scalable amounts of epithelial stem cells that are capable of generating the epithelial component of hair follicles, Xu says. And those cells have many potential applications, he adds, including wound healing, cosmetics, and hair regeneration.

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Converting Adult Human Cells to Hair-Follicle-Generating Stem Cells

Could the cure for baldness be found within our own skin?

For the first time, researchers from the Perelman School of Medicine at the University of Pennsylvania were successfully able to take human skin cells and transform them into hair-follicle-generating stem cells. These cells were then transplanted onto mice, and turned into human-like skin and hair follicles. The mice eventually grew tiny hair shafts.

The study was published Jan. 28 in Nature Communications.

The researchers began by using a type of skin cell known as dermal fibroblasts. They added three genes in order to transform them into induced pluripotent stem cells (iPSCs). These stem cells have the ability to transform into other cells found throughout the body.

Specifically, the iPSCs in this study were made into epithelial cells, which make up connective, muscle and nerve tissue. These cells are normally found at the bulb-like ends of hair follicles. The team was able to accomplish this by controlling the cells' growth time, and were able to turn 25 percent of the iPSCs into epithelial stem cells in about 18 days.

The epithelial stem cells were then mixed with mice hair follicle skin cells. They were then transplanted onto mice who had their immune systems suppressed. The cells produced human outer skin layer cells and follicles that were close to actual human hair follicles, which then grew the beginning of the hair shafts.

Dr. Xiaowei George Xu, associate professor of pathology, laboratory medicine and dermatology at the Perelman School of Medicine, said in a press release that these cells may be able to do more than generate hair. They could also be used in wound care and in cosmetics.

This is the first time anyone has made scalable amounts of epithelial stem cells that are capable of generating the epithelial component of hair follicles, Xu explained.

But, the research is still far from practical use. The next step is to create the other type of cell found in hair, dermal papillae, which are small bumps of cells found in the second layer of skin that poke into the top layer of skin. These dermal papillae create our fingerprints, among other things. For the experiments, the researchers used mice cells to make up for the lack of human ones.

When a person loses hair, they lose both types of cells, Xu said. We have solved one major problem, the epithelial component of the hair follicle. We need to figure out a way to also make new dermal papillae cells, and no one has figured that part out yet.

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Bye bye baldness? Researchers regrow hair using skin cells