Stem Cell-based Baldness Cure One Step Closer


Scientists might be able to offer people with less that optimal amounts of hair new hope when it comes to reversing baldness. Researchers from the University of Pennsylvania say they’ve moved closer to using stem cells to treat thinning hair — at least in mice.

This group said that the use of stem cells to regenerate missing or dying hair follicles is considered a potential way to reverse hair loss. However, the technology did not exist to generate adequate numbers of hair-follicle-generating stem cells.

But new findings indicate that this may now be achievable. “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,” Dr. Xiaowei Xu, an associate professor of dermatology at Penn’s Perelman School of Medicine, said in a university news release.

According to Xu, those cells have many potential applications that extend to wound healing, cosmetics and hair regeneration.

In their new study, Xu’s team converted induced pluripotent stem cells (iPSCs) – reprogrammed adult stem cells with many of the characteristics of embryonic stem cells – into epithelial stem cells. This is the first time this has been done in either mice or people.

The epithelial stem cells were mixed with certain other cells and implanted into mice. They produced the outermost layers of the skin and hair follicles that are similar to human hair follicles. This study was published in the Jan. 28 edition of the journal Nature Communications.

This suggests that these cells might eventually help regenerate hair in people.

Xu said this achievement with iPSC-derived epithelial stem cells does not mean that a treatment for baldness is around the corner. Hair follicles contain both epithelial cells and a second type of adult cells called dermal papillae.

“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.”

Experts also note that studies conducted in animals often fail when tested in humans.

Adult Stem Cells Suppress Cancerous Growth While Dormant


William Lowry and his postdoctoral fellow Andrew White at UCLA’s Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have discovered the means by which particular adult stem cells suppress their ability to trigger skin cancer during their dormant phase. A better understanding of this mechanism could provide the foundation to better cancer-prevention strategies.

This study was published online Dec. 15 in the journal Nature Cell Biology. William Lowry, Ph.D. is an associate professor of molecular, cell and developmental biology in the UCLA College of Letters and Science.

Hair follicle stem cells are those tissue-specific adult stem cells that generate the hair follicles. Unfortunately, they also are the cell population from which cutaneous squamous cell carcinoma, a common skin cancer, begins. However, these stem cells cycle between active periods, when they grow, and dormant periods, when they do not grow.

Diagram of the hair follicle and cell lineages supplied by epidermal stem cells. A compartment of multipotent stem cells is located in the bulge, which lies in the outer root sheath (ORS) just below the sebaceous gland. Contiguous with the basal layer of the epidermis, the ORS forms the external sheath of the hair follicle. The interior or the inner root sheath (IRS) forms the channel for the hair; as the hair shaft nears the skin surface, the IRS degenerates, liberating its attachments to the hair. The hair shaft and IRS are derived from the matrix, the transiently amplifying cells of the hair follicle. The matrix surrounds the dermal papilla, a cluster of specialized mesenchymal cells in the hair bulb. The multipotent stem cells found in the bulge are thought to contribute to the lineages of the hair follicle, sebaceous gland, and the epidermis (see red dashed lines). Transiently amplifying progeny of bulge stem cells in each of these regions differentiates as shown (see green dashed lines).
Diagram of the hair follicle and cell lineages supplied by epidermal stem cells. A compartment of multipotent stem cells is located in the bulge, which lies in the outer root sheath (ORS) just below the sebaceous gland. Contiguous with the basal layer of the epidermis, the ORS forms the external sheath of the hair follicle. The interior or the inner root sheath (IRS) forms the channel for the hair; as the hair shaft nears the skin surface, the IRS degenerates, liberating its attachments to the hair. The hair shaft and IRS are derived from the matrix, the transiently amplifying cells of the hair follicle. The matrix surrounds the dermal papilla, a cluster of specialized mesenchymal cells in the hair bulb. The multipotent stem cells found in the bulge are thought to contribute to the lineages of the hair follicle, sebaceous gland, and the epidermis (see red dashed lines). Transiently amplifying progeny of bulge stem cells in each of these regions differentiates as shown (see green dashed lines).

White and Lowry used transgenic mouse models for their work, and they inserted cancer-causing genes into these mice that were only expressed in their hair follicle stem cells. During the dormant phase, the hair follicle stem cells were not able to initiate skin cancer, but once they transitioned into their active period, they began growing cancer.

Dr. White explained it this way: “We found that this tumor suppression via adult stem cell quiescence was mediated by PTEN (phosphatase and tensin homolog), a gene important in regulating the cell’s response to signaling pathways. Therefore, stem cell quiescence is a novel form of tumor suppression in hair follicle stem cells, and PTEN must be present for the suppression to work.”

Retinoids are used to treat certain types of leukemias because they drive the cancer cells to differentiate and cease dividing. Likewise, understanding cancer suppression by inducing quiescence could, potentially, better inform preventative strategies for certain patients who are at higher risk for cancers. For example, organ transplant recipients are particularly susceptible to squamous cell carcinoma, as are those patients who are taking the drug vemurafenib (Zelboraf) for melanoma (another type of skin cancer). This study also might reveal parallels between squamous cell carcinoma and other cancers in which stem cells have a quiescent phase.

Reactivation of Hair Follicle Stem Cells Restarts Hair Growth


Sarah Millar and her team at the Perelman School of Medicine at the University of Pennsylvania have exploited a known property of hair follicle stem cells to restart hair growth in laboratory animals.

The Wnt signaling pathway is an important regulator of hair follicle proliferation, but does not seem to be required for hair follicle survival. Wnt signaling in cells culminated in the activation of a protein called beta-catenin, which goes to the nucleus of the cell and causes changes in gene expression.

wnt signaling

Millar and her colleagues disrupted Wnt signaling in laboratory animals by expressed an inhibitor called Dkk1 in hair follicles. Dkk1 expression prevented hair growth, and when the hair follicles were examined, they still had their stem cell populations, but these stem cells were dormant. Removal of Dkk1 resumed Wnt/beta-catenin signaling, and restored hair growth.

Dkk1 activity

Interestingly, Millar’s group found Wnt activity in non-hairy regions of the skin, such as palms, soles of feet, and so on. Therefore, in order for Wnt signaling to induce hair growth, it must occur within specific cell types.

This work also has additional applications: skin tumors often show over-active beta-catenin. Removing beta-catenin could prevent the growth of skin tumors, just as removing beta-catenin in the skin of these mice prevented proliferation of any hair follicles. However, agents that can activate beta-cateinin in hair follicles could reactivate dormant hair follicles and induce new hair growth.

Finding ways to safely reactivating the Wnt pathway in particular cells in the skin is a major focus of Millar’s research group.  Such work may lead to treatments for male pattern baldness.