Detailed information about hair follicle inductive cells

Inductive Cells

It has been demonstrated that hair follicle epithelial stem cells divide and produce new hair follicle cells but they need a push to actually do that. This push is provided by ‘inductive’ dermal cells.

Recent advances in epithelial stem cell biology have resulted in the isolation of hair follicle stem cells, which generate hair follicles when injected into immunodeficient mice. However, these isolated hair follicle epithelial stem cells must be combined with ‘inductive’ dermal cells to produce new hair follicles.

The advent of techniques for cultivating inductive dermal cells and competent epithelial stem cells creates the opportunity to bioengineer hair follicles for the treatment of hair loss.

Inductive ability of dermal cells

Several research investigators have found that a follicular dermal papilla dissected from the base of an adult anagen hair follicle, either fresh or after tissue culture expansion, could induce new hair follicle formation in rodents if placed in proximity to the epithelium.

This inductive ability of dermal cells is also apparent from the work of some scientists who transplanted the connective tissue sheath, a structure contiguous to the papilla, from the scalp of a man to the forearm of a woman.

Remarkably, 3–5 weeks later new hair follicles were found at the site of implantation.

The mesenchymal portion of the ‘new’ follicle arose from the donor male follicle, but the origin of the epithelial portion was not clear. An existing small follicle may have converted to a large hair follicle by the implanted sheath cells, or the interfollicular epidermis in the recipient’s arm may have generated a hair follicle de novo in response to the inductive dermal signals.

Whatever the mechanism, the powerful inductive ability of the follicular dermal cells is incontrovertible.

One approach to hair follicle cell-based therapy would entail removing a small number of hair follicles, isolating competent and/or inductive cells from them, and then expanding those cells ex vivo while maintaining their special ability to generate new hair follicles.

Clearly, cell culture conditions that maintain the inductive ability of dermal follicular cells and the competence of hair follicle epithelial cells are necessary before any type of cell-based therapy for alopecia can be developed. As early studies showed that the inductive property of dermal cells wanes with time in vitro, much research has focused on maintaining the trichogenic properties of hair follicle cells in culture.

Necessity of WNT pathway to maintain inductive ability

Seminal work by scientists showed that the WNT pathway is necessary for maintaining the inductive ability of cultured papilla cells; this finding allowed the generation of large numbers of inductive dermal cells from a small number of donor hair follicles.

Similarly for epithelial cells, researchers showed in mouse that cloned bulge cells can be amplified in culture using standard techniques with feeder cells, and then used in reconstitution assays to regenerate new hair follicles when combined with neonatal dermal cells. However, whether non-bulge keratinocytes possess similar properties was not reported. Future studies addressing these issues, especially in human systems, are necessary.

Bioengineering the hair follicle

For bioengineering the hair follicle, one could start with dermal elements from dissociated follicles with or without competent cells from the follicle or other epithelial sources. The number of dissociated cells would be expanded in culture and then dermal cells alone, or in combination with competent epithelial cells, re-introduced to the alopecic scalp.

Previous studies have shown that starting with correctly placed inducer dermal cells will result in new follicle formation. Moreover, starting with a combination of dissociated, or aggregated, trichogenic epithelial and dermal cells has also proven to be an effective method of producing new hair follicles.

The hair follicle reforms itself by means of interactions between competent epithelial stem cells and powerfully inductive dermal cells during its growth cycle. A product designed to form new hair follicles could be conceived to have the competent epithelial cells, the inductive dermal cells or perhaps a combination of both, delivered to the correct layer of the dermis.