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HAIR FOLLICLE
CLONING: A SUMMARY OF THE
RECENT LITERATURE
Richard P. Giannotto, MD
President and Medical Director
Hair Restoration Medical Group, PC
8201 Greensboro Drive Ste 609
McLean, Virginia 22102 USA
http://www.hrgnova.com
drgiannotto@hrgnova.com
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:
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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.
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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.
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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.
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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.
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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.
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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.
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