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Bioengineering the hair follicle

Scientists believe they may have found a new way to reverse baldness and treat conditions like premature balding and alopecia, which is a partial or complete loss of hair that may result from radiation therapy to the head, chemotherapy, skin disease or drug therapy. Hair grows from follicles and new follicle cells are born from stem cells that exist in a small bulge on the side of the hair follicle. The innate ability of the hair follicle to regenerate has led researchers and scientists to the conclusion that there is a possibility of producing new hair follicles through tissue engineering and stem cell technology.

Stem cells

No other area of scientific study has spawned as much intrigue, excitement and controversy than stem cells. In-depth research on stem cells has given humans advancing knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. This spectrum of futuristic science is also showing scientists and researchers the path to develop regenerative or reparative medicine or cell-based therapies to treat diseases.

In their endeavor to seek answers to fundamental questions in relation to long-term renewal of stem cells, scientists all over the world are successfully growing these cells in the laboratory and in turn using them for various tissue engineering and cellular therapies including baldness.

So, what exactly are stem cells? Stem cells differ from other kinds of cells in the body and irrespective of their source, have three general properties: they are capable of dividing and renewing themselves for long periods; they are unspecialized; and they can choose to become one of the many different types of cells present in the body based on signals from their environments.

Hair Follicle stem cells

Investigations and research by scientists in the field of stem cell therapy have proven that creation of new hair follicles through tissue engineering is possible. The investigators have identified the critical molecules that act under genetic instruction to direct the genes directly involved in hair follicle regeneration. In research with mice, investigations revealed that tweaking of the genes could produce furry mice or bald mice. This scientific breakthrough has enabled the possibility of development of extra hair follicles or impairment of the development of hair follicles in humans as well.

How do hair follicles regenerate?

The hair follicle is a tiny organ with the inherent power of being able to regenerate itself. At the base of the follicle is the hair bulb, where wildly growing matrix cells become hair in a series of intriguing steps. A little farther up the follicle is the mysterious feature called the bulge, where the follicle stem cells are ensconced. When stem cells receive the right set of chemical signals, these self-renewing cells divide. One half of the follicle stem cell splits into new cells that continue to split and develop. The other half becomes a new stem cell, and stays in place for future regeneration.

Hair Follicle Bioengineering Hurdles

The ideology behind bioengineering hair follicles is to harvest healthy follicle stem cells. The challenge, however, lies not in harvesting the cells, but in duplicating them. Unfortunately, during the multiplication process the cells shed the genetic code that directs them to turn into hair follicles.

Scientists have been working step by step towards cracking the molecular orchestration code. Instead of transplanting them right away, researchers have learned how to make the stem cells or seeds multiply successfully by identifying the signaling molecules that are responsible for development of epithelial buds, the precursor to hair follicle formation. The new follicle stem cells that are grown in laboratory cultures are attached then to tiny skin-cell scaffolds and implanted into bald areas of the scalp.

The technical hurdle that scientists and researchers are confronted with is defining the process of how these chemical signals act, how they initiate the migration of stem cells and progenitor cells to areas where they are required, and how these cells are ultimately differentiated into the specialized cells of the layers of the hair follicle.

The reason the solution has been so elusive is also the fact that laboratory animal studies do not always translate into humans. Most folliculoneogenesis studies have so far been successfully conducted on animals, and only after a clinical study can scientists say with conviction that bioengineering of the hair follicle is achievable.

It has long been known that hair follicle development begins in the very early embryo. In the fetus, there is an exchange of molecular “signals” between the epidermal or outer layer and underlying mesenchymal layers of cells that causes the formation of a “bud” in the epidermal layer. The fact that under normal circumstances, new hair follicles do not develop in an adult makes the process of bioengineering new hair follicles even more challenging.

Getting to the core of the matter

The overall goal is the indisputable revelation that cultured human cells can induce new follicle formation and hair growth in human skin. Ultimately the hope is that the research can be used successfully to cure such conditions as premature balding and alopecia and offer solutions for hair loss due to chemotherapy, rather than from the cosmetic angle.

It is a well-established fact that adult hair follicles do not grow and produce hair continuously but undergo intermittent phases of regression before resuming a new growing phase. This entire process is termed the follicle growth cycle. It is imperative that the principal cell types in the follicle retain powerful interactive signaling properties to maintain and control this composite series of events. Scientists have been triumphant in isolating dermal cells from the base of rodent follicles and shown that small collections of these cells can induce new hair follicles when combined with the epidermis.

There are two possible scenarios for using dermal inductive cells to generate new follicles in bald scalps. Research has demonstrated that the dermal cells from the base of the hair follicle, the dermal papilla cells are the key to the formation of hair follicles and to control hair growth in mature follicles. Dermal inductive cells are a group of specialized cells at the base of the hair follicle that give rise to the hair follicle at birth and supply the materials necessary for hair growth during the life of the person.

One approach to hair follicle cell based therapy would involve removing a small number of hair follicles, isolating inductive cells from them, and multiplying those cells while maintaining their ability to regenerate new hair follicles. The other approach actually entails forming hair follicles in vitro (biological phenomena that are made to occur outside the living body), and then transplanting the newly generated follicles back to the scalp.

In fact, Kurt S Stenn and Dr. George Cotsarelis have raised the question that since the competence to form follicles is not exclusive to bulge cells, there is a possibility that even other types of stem cells could be coerced into forming hair follicles by proper inductive cells.

Conclusion

No one can predict how soon dermatologists and pharmaceutical companies will be able to make use of the discoveries emerging from basic research into hair follicle development and cycling. However, by working on cell types that “know” how to form a hair follicle, researchers and scientists have made remarkable progress and provided inspiration for future therapeutic application.


Bioengineering the hair follicle references

  • Stenn KS, Cotsarelis G. Bioengineering the hair follicle: fringe benefits of stem cell technology. Curr Opin Biotechnol. 2005 Oct;16(5):493-7. PMID: 16098737
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