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.
The potential candidate cells in the hair follicle include:
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.
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.
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.
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.)