Dermal Papilla

Columbia University Study on 3-D Cultures is ‘Substantial Step Forward’ Towards Cloning Human Hair

For four decades, scientists have known about the possibility of using cells derived from the base of hair follicles (dermal papilla cells) to stimulate the growth of new hair. More recently, researchers have been able to harvest dermal papillae, multiply them, and induce the creation of new hair follicles – but only in rats. Now, for the first time, scientists at Columbia University have shown in a new study that they can induce new human hair growth from cloned human papillae. This procedure, called “hair follicle neogenesis,” has the potential to solve one of the primary limitations in today’s surgical hair restoration techniques; namely, the patient’s finite donor hair supply that is available for transplantation.

A significant number of hair loss patients do not have enough donor hair to be candidates for a hair transplant procedure with the percentage of women lacking stable donor hair greater than in men. This technique would enable both men and women with limited donor reserves to benefit from hair transplant procedures and enable current candidates to achieve even better results.

According to co-study leader Angela M. Christiano, Ph.D., of Columbia University in New York, the ground-breaking publication is a “substantial step forward” in hair follicle neogenesis. While the technology still needs further development to be clinically useful, the implications of successfully inducing new hair follicles to grow from cloned hair cells could be a game-changer in the arena of hair restoration. Instead of moving hair follicles from the donor area to the recipient area, as in a hair transplant, follicular neogenesis involves the creation of new follicles, literally adding more follicles to the scalp rather than merely transplanting them from one part of the scalp to another. Regarding the new technique’s possible use as a hair restoration treatment, Dr. Christiano said:

“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.”

In hair follicle neogenesis, the physician would harvest a sample of healthy, hair-producing scalp tissue from a patient. The dermal papilla cells in the samples would be isolated and allowed to multiply in a laboratory culture, and then the lab-grown papillae would be injected back into balding areas of the person’s scalp where they would induce skin cells to form into hair follicles that would grow normal adult hairs.

The main hurdle that researchers had to overcome was getting human papillae to aggregate — or clump together — so that it could then develop into a follicle. Cells that are cultured on a flat surface seem to lose their ability to produce hair. Prior studies have shown that rat papillae, unlike human papillae, tend to aggregate spontaneously; a process that makes the next, critical step of forming the hair follicle possible. The research team reasoned that if they could create an extracellular environment in which human cells could aggregate, they could induce the growth of human hair follicles.

The breakthrough came as a result of encouraging human dermal papillae cells to grow in a three-dimensional culture — a spherical mass of cells — rather than in a conventional two-dimensional tissue culture. The 3-D configuration allows the cells to signal one another and direct the formation of a new hair. Normally, a culture is grown in a one-cell layer in a petri dish, however, in order to coax the papillae to aggregate, the researchers used a technique called a “hanging drop culture.” Here, droplets of culture, each containing the requisite number of papilla cells (about 3,000 cells) to form a hair follicle, are placed on the lid of a petri dish. When the lid is flipped upside-down, the force of gravity pulls the papillae into the bottom of the suspended droplet, causing the cells to ‘clump.’ This is similar to what the rat papillae do naturally.

In the study, Christiano and colleagues took dermal papillae from seven donors and cloned the cells in tissue culture. After a few days, the cells were transplanted into human skin that had been grafted onto the backs of mice. In implanting these cultured ‘clumps’ of dermal papillae, the research team induced hair follicle production in five out of seven test samples. Using a technique called gene expression analysis, the researchers were able to determine that the three-dimensional cultures restored 22% of the gene expression found in normal hair follicles, enough to induce the formation of new hairs that genetically matched the human donor’s DNA (rather than the mouse).

While hair cloning and multiplication techniques have been discussed and studied for years, the progress made by Dr. Christiano and her colleagues Colin Jahoda, Ph.D., and Claire Higgins, Ph.D. (the first author on the study), is unprecedented. In identifying the key benefit their procedure might have over current hair restoration practices, Dr. Christiano said:

“Current hair-loss medications tend to slow the loss of hair follicles or potentially stimulate the growth of existing hairs, but they do not create new hair follicles. Neither do conventional hair transplants, which relocate a set number of hairs from the back of the scalp to the front. Our method, in contrast, has the potential to actually grow new follicles using a patient’s own cells.”

In addition to combating male and female pattern genetic hair loss (androgenetic alopecia), the technique has the potential for use as a treatment for patients with severe skin injuries, such as burn victims, or sufferers of chronic conditions like scarring alopecias. In these cases, the absence of hair follicles had limited the usefulness of transplanted skin. With the ability to clone follicles, this problem can potentially be overcome.

Dr. Christiano, a colleague of Dr. Bernstein’s at Columbia University, is a world-renowned hair geneticist and a sufferer of alopecia areata, an autoimmune disease that creates bald spots on the scalp. In investigating the causes of her own balding, Dr. Christiano embarked on a career that led to she and her team identifying multiple genes associated with the disease. Her co-study leader, Dr. Jahoda, is a professor of stem cell sciences at Durham University and co-director of the North East England Stem Cell Institute. The lead author of the study, Dr. Higgins, is an associate research scientist in the dermatology department at Columbia University.

The study called, “Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth,” and published in the Proceedings of the National Academy of Sciences (PNAS). The human hair follicles in this study were donated by volunteer hair transplant patients at Bernstein Medical – Center for Hair Restoration in New York City. We are appreciative of our patients who participated in this research.

Reference
Higgins, C.A., Chen, J.C., Cerise, J.E., Jahoda, C.A., Christiano, A.M.: Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth. PNAS, 2013; doi: 10.1073/pnas.1309970110.