SUMMARY OF THE ARTICLE PUBLISHED IN THE INTERNATIONAL HAIR FORUM MARCH/APRIL 2004 VOLUME 14, NUMBER 2
FOLLICULAR CELL IMPLANTATION: AN UPDATE ON “HAIR FOLLICLE CLONING”
Jerry Cooley, MD Charlotte, North CarolinaDisclosure: Dr. Cooley is a consultant for Intercytex, Ltd., a Manchester, U.K. based company which is developing a follicular cell.
The concept of culturing hair follicle cells in vitro and re-implanting them falls within the realm of cell therapy or tissue engineering. Use of the term “cloning” is actually not appropriate. “Cloning”, from the Greek word “twig,” means to create an exact genetic replica by asexual means. The use of fetal or embryonic tissue is often an integral part of this technology. Scientists may refer to cloning a gene, cell, or whole organism, but tissue-engineered organs and tissues, such as hair follicles, are not generally referred to as clones.
Hair growth results from a dynamic interaction of epidermal and dermal components in the fetus and for normal hair shaft production during the anagen phase of the hair growth cycle.
Colin Jahoda and his colleagues showed that the cells of the rat whisker dermal papilla could be grown in vitro and that the cultured cells could induce hair growth when implanted into incisional skin wounds of the rat. Presumably the implanted cells were interacting with native epithelial cells to re-create hair follicles and produce a hair shaft. The process by which implanted cultured dermal papilla cells would induce hair growth is conceptually similar to what happens during fetal development of the hair follicle and the normal anagen phase of the growth cycle.
OBSTACLES AND CHALLENGES:
Research describing follicle induction using implanted follicular cells is almost 25 years old, and yet only inconsistent success in replicating this in humans has been achieved, highlights the complexity and challenges ahead.
WHICH FOLLICULAR CELLS MUST BE IMPLANTED?
The potential candidate cells in the hair follicle include:
- Dermal cells
- Dermal papilla
- Dermal sheath
- Interfollicular keratinocytes
- Outer root sheath
- Stem cells from the bulge
- Germinal epithelial cells
The original research by Jahoda indicated the dermal papilla alone may be capable of follicle induction. However, the dermal papilla may not be the ideal candidate and the most recent report by Jahoda showed that cultured dermal papilla failed to induce follicle formation in a wound model. Subsequent research has shown certain beneficial “stem cell”–like properties to the lower dermal sheath such as immunologic privilege, suggesting it may be superior to the papilla for follicle induction.
If dermal cells are implanted alone, they must somehow make contact with epidermal cells present in the recipient site skin. One way of overcoming this problem is to co-implant cultured epidermal cells, such as from the “bulge,” outer root sheath, or germinal epithelial cells located in the matrix. But including cultured epidermal cells raises a whole new set of problems that dramatically increases the complexity of the procedure.
MAINTAINING INDUCTIVE POTENTIAL:
One important finding of Jahoda’s research was that after several passages in culture, the papilla cells lost their ability to induce hair growth. Presumably, the cells were changing over time, becoming more like fibroblasts and less like hair-inducing papilla cells. A focus of current research is to identify the changes in gene expression that occur as dermal papilla cells are cultured over time.
WILL “CLONED HAIR” LOOK NORMAL?
Another important question is whether tissue-engineered hair will be cosmetically acceptable. Furthermore, the regenerated follicles must be oriented so that the hair grows at the proper angle and direction.
ECONOMIC AND REGULATORY HURDLES
The economic costs of developing a government approved cell culture therapy are substantial involveing costly bureaucratic requirements. Highly trained personnel to isolate and culture the follicular cells. These economic and regulatory hurdles may be as significant as the “scientific” hurdles.
Figure 1: Conceptual framework for follicular cell implantation. A small piece of skin containing hair follicles is removed from the occipital scalp. The cells of the hair follicle necessary for inducing follicle formation are isolated and grown in culture where they rapidly divide and multiply. The cells are then re-implanted in the skin where they induce new follicle formation resulting in new hair growth.
Figure 2: Fetal development of the hair follicle, as well as normal anagen hair growth, involves a complex interaction of epithelial (A) and mesenchymal(B) components. In cell therapy, the implantation of dermal papilla cells into the epidermis and subsequent induction of hair follicles mimics this natural process.
Figure 3: Schematic representation of the hair follicle, showing the location of cell types that might be used for cell implantation. GE cells = germinal epithelial cells.
Figure 4: Cultured human dermal papilla and epithelial cells implanted on to the backs of immune deficient mice retain their ability to induce follicle formation and produce hair despite being expanded in vitro. (Courtesy of Intercytex, Ltd.)