Currently, the standard approach for treating male pattern baldness is follicular unit hair transplantation, commonly referred to as FUT or “hair transplant.” This approach involves a surgical procedure in which healthy hair follicles are taken from a donor site and relocated to an affected area. While effective, this technique is not a cure for hair loss, as hair growth is not restored. Rather, existing hair follicles are redistributed in order to minimize the appearance of thinning hair. Additionally, not everyone is a good candidate for this procedure. Women, for example, tend to undergo a diffuse type of hair loss and suffer from a lack of stable donor sites from which grafts for transplantation can be obtained. Patients in the early stages or with excessive hair loss, patients suffering from scarring alopecia, and patients with hair loss due to burn wounds are also not good candidates for the procedure.
Recently, a research team has reported success in stimulating hair growth using cloned dermal papilla (DP) cells.1 These results have exciting implications for hair loss treatment practices. Rather than having to rely on surgical redistribution of existing hair follicles, treatment in the near future could make use of a patient’s own DP cells to stimulate the production of new hair, as well as rejuvenate hair follicles already in place.
A New Way to Trick Hair Follicles Into Producing More Hair
DP cells are specialized cells that reside within the hair follicle bulb. Among other important functions, DP cells send signals to epithelial stem cells to initiate and promote hair growth, making these cells ideal candidates for use in treating hair loss. The idea of cloning DP cells and using them to initiate hair growth is not new. Until recently, however, attempts to retrieve functional DP cells using standard cloning practices have been unsuccessful. One of the main setbacks encountered was trying to keep cloned cells from reverting back to basic skin cells. Angela Christiano, Ph.D., a professor at Columbia University and one of lead investigators in the current study, explained in an interview with “Men’s Health Online” that shortly after removal from the follicle, the cells could no longer recall that they were DP cells. Their cellular identity had basically been erased.2 DP cells require a number of chemical signals from neighboring cells in order to maintain their ability to stimulate hair growth. 3 Cells that have been removed from their natural environment and grown in culture – a procedural step required in order to increase the number of donor cells – no longer seem to receive these signals. As a result, DP cells revert back to basic skin cells and lose the critical ability to stimulate hair growth.
To solve this problem, the research team headed by Christiano in the United States and Colin Jahoda, M.D., Ph.D. at Durham University in the United Kingdom, took a closer look at what was happening during the cloning procedure. Specifically, they looked at how DP cells behave in culture. Traditional culture conditions yield a 2D matrix of cells that is very different from the natural, 3D environment from which the cells are derived. Previously, it had been shown that DP cells extracted from mice, which aggregate in culture to form 3D clumps or spheres, retain their cellular identity and are able to stimulate hair growth when transplanted back.4 Researchers hypothesized that, by forming aggregates, the cultured mouse cells are creating a microenvironment for themselves that mimicks the conditions from which they were originally obtained.
Hair Cloning May Arrive in 2014 After All!
Taking their cue from this observed behavior, the research team turned their attention to the growth pattern of human DP cells in culture. Unlike the mouse cells, human DP cells grow to form a 2D matrix when cloned. Researchers found a significant difference in the genes that are expressed in these cloned cells and those expressed in the original cells. Armed with this knowledge, they took the DP cells and grew them under conditions that promote 3D spheroid formation, rather than the traditional 2D matrix. By reprogramming the cells’ microenvironment in this way, researchers were now able to grow cells with a gene expression pattern similar to that of the original DP cells. In other words, the cells that grew in spheroids didn’t revert, but retained several of their original features.
Researchers examined the ability of these cultured cells to induce hair follicle growth. Remarkably, they discovered that the human DP cells that grew in spheroids were capable of initiating de novo hair follicle growth. What does this mean? It means that human DP cells can indeed stimulate new hair to grow if they are cloned under the appropriate growth conditions – in 3D spheroids.
The results are compelling and clear. When DP cells were transplanted between the dermal and epidermal layers of human skin grafted onto the backs of mice, five out of the seven DP cell populations were able to induce hair follicle growth. As much as six weeks after induction, hair follicles containing inner root sheaths and hair shafts could be seen growing on the human skin grafts.
Researchers verified their findings by analyzing the DNA of the new follicles. Test results showed that the follicles were, indeed, human and a genetic match with the donor cells, proving that the induced follicle growth was undoubtedly a product of the transplanted DP cells.
Previous studies have shown that human DP cells grown in a 3D environment can retain their growth-induction properties when introduced into mouse epidermal cells.5 This is the first time, however, that it has been demonstrated that cultured DP cells grown in such a way can induce hair follicle growth de novo when transplanted into human dermal layers (albeit human dermal layers that have been grafted onto a mouse.) To be clear, the spheroid-derived cells in this latest study were not implanted into existing hair follicles, mouse or human. All of the resulting hair growth occurred from de novo follicles, and was directed entirely by transplanted DP cells.
The significance of these results is astounding to those with a vested interest in finding a better way to treat or reverse hair loss. This is the first time it has been shown that hair follicle growth can, indeed, be restored. Donor DP cells for procedures based on this technique could come from as little as a few hundred hairs, a vast improvement over the thousands of follicles currently needed for follicular unit hair transplantation. Such an advance would make treatment available to the previously mentioned groups of hair loss sufferers who don’t qualify for hair transplant surgery because they don’t have sufficient donor follicles.
The results of the study were announced in an advanced online communication and will appear in the latest issue of Proceedings of the National Academy of Science. While the findings indicate an important advance in the field of hair loss treatment, researchers caution that there is still some work to be done before human clinical trials can begin. Specifically, the source of certain physical properties of the newly induced hair, such as rate of growth, texture, and color are still unclear. Researchers are confident, however, that answers to these questions aren’t too far off. The announcement is a welcome and exciting one, not just for hair loss sufferers, but for the medical and scientific fields at large.
1. Higgins, C.A., et al. (2013) Proc Natl Acad Sci USA (epub ahead of print)
2. Behar, M. (n.d.) Men’s Health. MH Spoghtlight. Web. 26 Oct 2013
3. Rendl, M., et al. (2008) Genes & Dev 22:543-57
4. Inamatsu, M., et al. (1998) J Invest Dermatol 111:767-75
5. Kang, B.M., et al. (2011) J Invest Dermatol 137:232-39
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