Molecular Manipulation Induces Skin Cells to Produce Hair

Working with mouse skin cells, researchers have generated hair-producing follicles from newborn and adult cells and traced the molecular pathways that control their development.

Investigators at the University of Southern California (Los Angeles, USA) were particularly interested in determining whether adult skin cells could be transformed into hair-producing follicles. Towards this end, they began with an in depth imaging analysis of skin cells from newborn mice during the process of forming three-dimensional, hair-producing organoids.

Observations described in the August 10, 2017, online edition of the journal Proceedings of the [U.S.] National Academy of Sciences revealed that skin cells from newborn mice formed organoids by transitioning through six distinct phases: 1) dissociated cells; 2) aggregated cells; 3) cysts; 4) coalesced cysts; 5) layered skin; and 6) skin with follicles, which robustly produced hair after being transplanted onto the back of a host mouse. These physical manifestations were driven at the molecular level by the sequential expression of adhesion molecules, growth factors, Wnt signaling proteins, and matrix metalloproteinases (MMPs).

In contrast, skin cells from adult mice formed small aggregates, but then development stalled when grown in vitro cultures. Findings from the newborn cells study enabled the investigators to develop a strategy to restore morphological transitions and rescue the hair-forming ability of adult organoids: (i) continuous PKC (Protein kinase C) inhibition and (ii) timely supply of the growth factors IGF (Insulin-like growth factor) and VEGF (Vascular endothelial growth factor), Wnts, and MMPs.

By providing the correct molecular and genetic cues in the proper sequence, the investigators were able to stimulate adult organoids to continue their development and eventually produce hair. Ultimately, adult organoids produced about 40% as much hair as the newborn organoids.

"Normally, many aging individuals do not grow hair well, because adult cells gradually lose their regenerative ability," said senior author Dr. Cheng-Ming Chuong, professor of pathology at the University of Southern California. "With our new findings, we are able to make adult mouse cells produce hair again. In the future, this work can inspire a strategy for stimulating hair growth in patients with conditions ranging from alopecia to baldness."

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