Dermal stem cell precursors show promise for therapeutic applications

Key Points

Freda Miller, Ph.D., professor, molecular and medical genetics, University of Toronto, says she and co-investigators have discovered cells in hair follicles that appear to function like dermal stem cells and will likely have potential applications in various areas of medicine.

"We were very interested in finding an accessible source for human nervous system therapies," says Dr. Miller, who reviewed her current and prior research at the recent meeting of the International Society for Stem Cell Research here.

"The dream is that you can take advantage of the stem cells that we now know live in many of your tissues and somehow activate them or wake them up to repair and regenerate tissues," she says.

Dr. Miller and co-investigators have conducted research that demonstrated that cultures of multipotent precursors can be grown from the dermis of neonatal and adult mammalian skin.

The SKPs represent a novel precursor cell type, distinguishable from other known precursors within the skin (Toma JG, et al. Nat Cell Biol. 2001;3(9):778-784; Toma JG, et al. Stem Cells. 2005;23(6):727-737; Fernandes K, et al. Nat Cell Biol. 2004;6(11):1082-1093).

Researchers also have shown that Sox2+ precursors are endogenous dermal stem cells, and can induce hair morphogenesis as well as maintaining the dermis (Biernaskie J, et al. Cell Stem Cell. 2009;5(6):610-623).

"We have shown this in mice and rats," Dr. Miller says, referring to the induction of hair morphogenesis. "We don't know if it will be the case in humans or not. If so, it could be used for alopecia or chemotherapy-induced hair loss."

Dr. Miller and colleagues are currently screening different compounds to determine which ones might activate the SKPs to have bioactivity. Dr. Miller envisions a compound or lotion that would be applied to the scalp in terms of a possible therapy to treat alopecia.

"It could penetrate to the precursors, kick them into gear, and help them grow a bit more," she says.

In terms of wound healing, Dr. Miller says SKPs may play a role in the development of adjuncts to skin grafts for various injuries.

"There may be a topical compound that would encourage the reparative process," she says. "We could use our cells to help make dermal portions of artificial skin."

The understanding of SKPs and how to promote their activity may present opportunities for therapies targeting anti-fragility of skin as skin ages, according to Dr. Miller.

Dr. Miller and colleagues transplanted SKPs, purified SKP-derived Schwann Cells (SCs) and CNS SVZ neurospheres into the contused rat spinal cord in order to compare neuroanatomical and functional outcomes. They found that the SKP-SCs demonstrate improved survival related to CNS neural stem cells. In addition, transplanted naive SKPs also respond to endogenous cues in the injured peripheral nerve and differentiate into SCs that myelinate spared and/or regeneration axons (Biernaskie J, et al. J Neurosci. 2007;27(36):9545-9559. McKenzie IA, Biernaskie J, Toma JG, et al. J Neurosci. 2006;26(24):6651-6660).