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HAIR FOLLICLE CLONING: A Summary of the Recent Literature

by Richard P. Giannotto, MD
President and Medical Director
Hair Restoration Medical Group, PC
McLean, Virginia 22102 USA

There are many limitations to cosmetic, medical and surgical treatment methods currently in use for hair loss. Newer treatment methods will eventually emerge, which potentially have the ability to “cure” inherited patterned baldness permanently. These methods encompass the concepts of Hair Follicle Cloning and Gene Therapy.

Hair follicles are miniature hair growing organs which evolve through growth and rest cycles. In addition to hairs being grown and then shed in these phases, the follicle itself disintegrates almost entirely by the end of the regression phase, and an almost entirely new follicle is created at the beginning of the next growth phase. This presents a unique opportunity for applying advanced molecular biological and medical techniques resulting in cloning and gene therapy.
 

Cell Biology and Genetics

Cells are the basic unit of all living organisms. The hair follicle is a miniature organ in which there are several different types of cells working together to grow a hair. Inside of every cell there is a NUCLEUS that contains CHROMOSOMES composed of DNA, the genetic material of the cell. Genes are sections of DNA that contain the code for particular types of proteins. Proteins, in turn, determine actual characteristics such as hair color, eye color, baldness, etc.

Each cell in a multi-cellular organism contains in its chromosomes a COMPLETE DNA BLUEPRINT of all of the genes for the proteins for the entire organism. Unlocking this DNA information in mature specialized cells is an important aspect of some cloning techniques.
 

Cell Replication

In a rapidly growing embryo, cells replicate by splitting in half and then growing to full size again. This process is called cell MITOSIS. Each half of a cell that splits contains a complete and exact set of the organism’s DNA. As the embryo grows into a more fully functional organism, its cells begin to take on more specialized characteristics and begin to divide less. As cells become more specialized, cell replication shifts to more specialized cells called STEM CELLS. As specialized cells wear out over time they must be replaced from this pool of stem cells, which can create many different types of specialized cells.
 

CLONING

The background of cellular biology as presented above forms the scientific basis for cloning. Cloning is defined as the creation of an EXACT GENETIC REPLICA BY ASEXUAL MEANS. The use of fetal or embryonic tissue is an integral part of this technology. Scientists CLONE a gene, a cell or an entire organism.

Cloning as defined above must be distinguished from TISSUE ENGINEERING or CELL THERAPY. Tissue engineering involves culturing cells in vitro and re-implanting them. An example of such a tissue that could potentially be cultured and implanted is Hair Follicles. Tissues such as hair follicles are not referred to as clones.

In an imperfect world however, the following terms have become interchangeable: Hair Follicle Cloning, Follicular Cell Implantation, Follicular Neo-genesis, Follicular Regeneration and Hair Multiplication. According to scientific protocol however, the first term, cloning, should be excluded from the list, as it is tissue engineering that forms the basis for the technique described herein.

Why then, is research proceeding along these lines? What is the driving force and/or rationale for tissue engineering or cloning? First, there is the promise of UNLIMITED DONOR HAIR. There have been countless times that a patient has been deemed not a suitable candidate for surgical hair restoration due to the sparseness and quality of the donor hair. This would never occur in light of unlimited donor. A second driving force would be the LACK OF A DONOR SCAR. This would please many patients and physicians alike. The CREATION OF GREATER DENSITY and a more EASILY TOLERATED PROCEDURE also make the concept of cloning attractive to clinicians.
 

THE CONCEPT

Theoretically, the concept of tissue engineering would involve harvesting a small sample of hair follicles from the same donor region used in hair transplantation. The follicle inducing cells in the hair follicle would be isolated and subsequently caused to multiply using a cell culture. The newly multiplied cells would then be re-implanted into the recipient area of the scalp so that new follicles are created. Because of the cell division that occurs while culturing, countless new cells are created that when implanted, result in hundreds of NEW HAIR FOLLICLES.
 

BACKGROUND

The basis for Follicular Cell Implantation (FCI) began in the fundamental investigation of normal hair growth. Hair growth results from a DYNAMIC INTERACTION of epidermal and dermal components. This DERMAL-EPIDERMAL INTERACTION is what determines follicular development in the fetus, as well as normal hair shaft production during anagen.
Colin Jahoda showed the validity of this interaction by taking cells of the rat whisker dermal papilla, growing these cells in culture and implanting the cultured cells into incisional skin wounds of the rat. The implanted cells induced hair growth by interacting with native epithelial cells to re-create hair follicles and produce a hair shaft. This is similar to what happens during FETAL DEVELOPMENT of the hair follicle and the normal ANAGEN PHASE of the growth cycle. Several investigators, including Jahoda, Cooley and Vogel, Unger, and the Aderans Research Institute have replicated this work in humans. The problem is that nothing has appeared in the way of detailed studies to describe the actual TECHNIQUES used in these human studies. Because of the inherent commercial value of successful research, the importance of protecting intellectual property has overshadowed the impetus to publish.
 

APPLICATIONS

Using TISSUE ENGINEERED cells to treat hair loss is conceptually quite simple, but many complexities and challenges obscure this application. Research efforts span over twenty years yet the results have been inconsistent at best. This points to various OBSTACLES that have yet to be overcome. A sampling of the major concerns are as follows:

Autologous vs Allogenic Tissue: Must the tissue used be that from the individual who will undergo the procedure or can tissue from another individual be used to create engineered follicles? Some portions of the hair follicle seem to be immunologically “privileged”, but whether allogenic tissue will work is unknown at this time.

Which follicular cells must be cultured and implanted? There is controversy regarding the type of cell to be cultured and implanted. Dermal cells, epidermal cells, stem cells and germinal epithelial cells all may have the potential to form new hair follicles when cultured, but there is no consensus on this in the research literature.

The ability to maintain inductive potential is an important factor in implanting tissue engineered follicles. After several passages in culture, papilla cells lose their ability to induce hair growth when re-implanted. This could potentially be a major obstacle for the development of a treatment for hair loss.

The cosmetic characteristics of the resultant cloned hair will be important. Color, orientation, curl and caliber of the hair will have to be analyzed such that a “normal” looking result is achieved.

There are economic and regulatory hurdles that need to be overcome before FCI is considered a treatment for hair loss. In the United States, the US Food and Drug Administration would likely regulate implanted hair cells as “Biologic Therapy”. This implies a comprehensive regulatory framework and significant legal hurdles which could potentially impede or delay FCI as therapy for hair loss.

Finally, there is the question of safety. There must be an investigation into whether or not FCI could result in a tendency toward tumor formation. The question of the transmission of infectious diseases, especially if allogenic tissue is utilized, will become of overriding importance in FCI therapy.
 

SUMMARY

FCI has the potential to overcome many of the limitations of current surgical hair restoration, especially the finite supply of donor hair. The basic concept is sound, but reports in humans show inconsistencies and problems with reproducibility. The prospect of an unlimited donor supply will continue to influence tissue engineering based research to overcome these obstacles.