Epithelial Cells - Bernstein Medical - Center for Hair Restoration
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Progress towards hair cloning may have just have shifted up another gear thanks to scientists at the University of Pennsylvania and the New Jersey Institute of Technology. The breakthrough study published January 28th, 2014 is the first to show the successful transformation of adult human skin cells into quantities of epithelial stem cells necessary for hair regeneration.

The researchers, led by Dr. Xiaowei “George” Xu, started with human skin cells called dermal fibroblasts, then transformed those into a type of stem cell called induced pluripotent stem cells (iPSCs). These were then transformed into epithelial stem cells (EpSCs). This important step had never been achieved before in either humans or mice. The epithelial stem cells were combined with mouse dermal cells, that can be induced to form hair follicles, and then grafted on a mouse host. The epithelial cells and dermal cells then grew to form a functional human epidermis and follicles structurally similar to human hair follicles. The exhibits that accompany the study include photographic evidence of human hairs.

Figure 5 - Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cellsHair shafts (arrowheads) formed by induced pluripotent stem cell-derived epithelial stem cells compared to mouse hair (arrows). — Credit: Ruifeng Yang, Perelman School of Medicine, University of Pennsylvania

The main breakthrough in the study came when the research team carefully timed the addition of growth factors to the iPSCs. Previous research showed the ability for iPSCs to be transformed into a common type of cell found in the skin called keratinocytes. By timing the addition of the growth factors, they were able to turn over 25% of the iPSCs into epithelial stem cells in a little more than two weeks. This “mass production” of epithelial stem cells holds tremendous promise for the development of a hair regeneration treatment. On this development, Dr. Xu said, “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.”

As noted in a University of Pennsylvania press release on the news, there are two types of stem cell that are critical in hair follicles: epithelial stem cells and dermal papillae. While this study only achieved success in the creation of epithelial stem cells, we have extensively covered Dr. Angela Christiano’s ground-breaking research into the induction of dermal papillae into hair follicles (a process she calls hair follicle neogenesis).

“When a person loses hair, they lose both types of cells. 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,” said Dr. Xu.

Once that it is done, we must also find a way to have the epithelial and dermal components of the follicle interact before one will be able to produce cosmetically useful hair. But with each successive breakthrough, the time when a scientist can use hair cloning techniques to regenerate human hair, and the surgeon can implant them into a person’s scalp, draws ever closer.

Reference
Yang R, Zheng Y, Xu X. Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cells. Nature Communications. 2014.

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Japanese Researchers Bioengineer Hair Follicles from Stem Cells, Dermal PapillaeCredit: Tokyo University of Science

Japanese researchers have demonstrated that scientists can bioengineer viable, hair-producing follicles from epithelial stem cells and dermal papilla cells. Using these components, the team produced follicles that exhibit both the normal hair cycle and piloerection (the reflex contraction of a tiny muscle in the hair follicles which creates what is commonly referred to as “goose bumps”). The bioengineered follicles also developed the normal structures found within follicles and formed natural connections with skin tissues, muscle cells, and nerve cells.

The scientists used a breakthrough type of hair multiplication to achieve a functional bioengineered hair follicle. In hair multiplication, germinative cells are harvested non-surgically and then multiplied outside the body in a laboratory. These cells are then injected into the skin where they, ideally, grow into hair follicles. The Japanese research team takes this concept one step further by first combining the stem cells and dermal papillae in the laboratory to create a germ of the hair follicle. This germ is then implanted into the scalp where it grows into a viable hair follicle.

The study opens the door to treat common baldness (androgenetic alopecia) and a host of other medical conditions that can cause hair loss.

View the Hair Cloning section to read more on hair multiplication and hair cloning methods.

Reference:

Koh-ei Toyoshima, Kyosuke Asakawa, Naoko Ishibashi, Hiroshi Toki, Miho Ogawa, Tomoko Hasegawa, Tarou Irié, Tetsuhiko Tachikawa, Akio Sato, Akira Takeda, Takashi Tsuji. Fully functional hair follicle regeneration through the rearrangement of stem cells and their niches. Nature Communications, 2012; 3: 784 DOI: 10.1038/ncomms1784

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Q: Like many people who are eagerly awaiting hair cloning, I read about ACell’s new technology, but what is an “extracellular matrix”? — S.B., Chicago, IL

A: An extracellular matrix, or ECM, is the substance between the cells in all animal tissues. It provides support to the cells and a number of other important functions. ECM is made up of fibrous proteins that form a web or mesh filled with a substance called glycosaminoglycans (GAG). One type of GAG, called hyaluronic acid, functions to hold water in the tissues. Another important part of the extracellular matrix is the basement membrane on which the epithelial cells of the skin and other tissues lie. Elastin in the ECM allows blood vessels, skin, and other tissues to stretch.

ECM has many functions including providing support for cells, regulating intercellular communication, and providing growth factors for wound healing and tissue regeneration.

Read more about ACell’s MatriStem ECM on our ACell for Hair Cloning page.

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Q: Considering cell cultivation is made possible how could their injection create a normal formation of hair on the scalp and can they induce hair growth also in scarred areas where previously hair stopped growing?

A: That is the question. It is not known if these induced follicles will resemble normal hairs, and be cosmetically acceptable on their own, or if they will grow unruly and must be used as a filler behind more aesthetically pleasing transplanted hair.

Hair growth is an interaction between the dermal components (fibroblasts in the dermal sheath and dermal papillae) and the epidermal structures.

It is possible that the injected dermal fibroblasts will interact with resident epithelial cells to produce a properly oriented hair. A tunnel of epithelial cells can also be created to facilitate this process and some researchers are using cultures of both dermal and epithelial cells.

As you suggest, part of the challenge is not just to multiply the hair but to find a way for the hair to grow in its proper orientation. With scar tissue, the task will obviously be much more difficult.

Another issue is that the induced follicles are just that, they are single hair follicles rather than complete follicular units. Because of this they wouldn’t have the cosmetic elegance of one’s own natural hair, unlike that which is possible in follicular unit hair transplantation.

That said, much work still needs to be done and it is not clear at this time what might be the solution.

Read more on the Hair Cloning page on the Bernstein Medical – Center for Hair Restoration website.

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