A team led by scientists at the University of Southern California (USC) published a study (“Self-Organization Process in Newborn Skin Organoid Formation Inspires Strategy to Restore Hair Regeneration of Adult Cells”) in Proceedings of the National Academy of Sciences that describes how the skin develops hair follicles that subsequently grow hair. The researchers carried out their work with 3D organoids.
Mingxing Lei, Ph.D., a post scholar in the stem cell lab of Cheng-Ming Chuong, M.D., Ph.D., and an international group of colleagues took dissociated skin cells from a newborn mouse and used time-lapse movies to study cell behavior. The cells formed organoids by going through six phases, i.e., dissociated cells, aggregated cells, cysts, coalesced cysts, layered skin, and skin with follicles that grew hair when transplanted to the back of a host mouse.
On the other hand, dissociated skin cells from an adult mouse only made it to the phase aggregation stage before stalling in development.
The researchers studied the molecular events and physical processes that led to successful organoid formation with newborn mouse cells by using a “a combination of bioinformatics and molecular screenings, and the core facilities at the Health Sciences Campus,” said Dr. Lei.
The team found increased activity in genes related to collagen, insulin, the formation of cellular sheets, the adhesion, death, or differentiation of cells, and other processes. They also discovered where in the organoid this activity took place. Finally, they blocked the activity of specific genes to certify their roles in organoid development.
The researchers said they created a molecular “how to” guide for making individual skin cells self-organize into organoids that can produce hair. Using this knowledge, they then focused on the stalled organoids derived from adult mouse skin cells. By providing the right molecular and genetic cues in the proper sequence, they were able to stimulate these adult organoids to continue their development and eventually produce hair, explained Dr. Chuong, adding that the adult organoids produced 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 Dr. Chuong, senior author, principal investigator, and professor of pathology at the Keck School of Medicine of USC. “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.”