Researchers at Columbia University Medical Center (CUMC) say they have come up with a hair restoration method that can generate new human hair growth, rather than simply redistribute hair from one part of the scalp to another. The approach could significantly expand the use of hair transplantation to women with hair loss, who tend to have insufficient donor hair, as well as to men in early stages of baldness, according to the investigators.
The study (“Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth”) was published today in the online edition of the Proceedings of the National Academy of Sciences (PNAS).
“This method offers the possibility of inducing large numbers of hair follicles or rejuvenating existing hair follicles, starting with cells grown from just a few hundred donor hairs. It could make hair transplantation available to individuals with a limited number of follicles including those with female-pattern hair loss, scarring alopecia, and hair loss due to burns,” explained co-study leader Angela M. Christiano, Ph.D., the Richard and Mildred Rhodebeck Professor of Dermatology and professor of genetics & development.
“Dermal papilla cells give rise to hair follicles, and the notion of cloning hair follicles using inductive dermal papilla cells has been around for 40 years or so,” added co-study leader Colin Jahoda, Ph.D., professor of stem cell sciences at Durham University in the U.K., and co-director of North East England Stem Cell Institute. “However, once the dermal papilla cells are put into conventional, two-dimensional tissue culture, they revert to basic skin cells and lose their ability to produce hair follicles. So we were faced with a Catch-22: how to expand a sufficiently large number of cells for hair regeneration while retaining their inductive properties.”
The researchers found a clue to overcoming this barrier in their observations of rodent hair. Rodent papillae can be easily harvested, expanded, and successfully transplanted back into rodent skin. The main reason that rodent hair is readily transplantable, the researchers suspected, is that their dermal papillae (unlike human papillae) tend to spontaneously aggregate, or form clumps, in tissue culture. The team reasoned that these aggregations must create their own extracellular environment, which allows the papillae to interact and release signals that ultimately reprogram the recipient skin to grow new follicles.
“This suggested that if we cultured human papillae in such a way as to encourage them to aggregate the way rodent cells do spontaneously, it could create the conditions needed to induce hair growth in human skin," said first author Claire A. Higgins, Ph.D., associate research scientist.
To test their hypothesis, the researchers harvested dermal papillae from seven human donors and cloned the cells in tissue culture; no additional growth factors were added to the cultures. After a few days, the cultured papillae were transplanted between the dermis and epidermis of human skin that had been grafted onto the backs of mice. In five of the seven tests, the transplants resulted in new hair growth that lasted at least six weeks. DNA analysis confirmed that the new hair follicles were human and genetically matched the donors.
“In this paper, we demonstrate that by manipulating cell culture conditions to establish three-dimensional papilla spheroids, we restore dermal papilla inductivity,” wrote the research team in PNAS. “We also use several systems biology approaches to gain a comprehensive understanding of the molecular mechanisms that underlie this regenerative process.”
The researchers relied on gene expression analyses to determine that the 3D cultures restored 22% of the gene expression seen in normal hair follicles. “That's less than we expected, but it was sufficient for inducing the growth of new hair follicles,” noted Dr. Christiano, who emphasized that more work needs to be done before the method can be tested in humans.