Q: I read, with considerable interest, your excellent article on the latest in Dr. Angela Christiano’s work on follicular neogenesis. It seems to me that the next questions we should be asking are: when will testing begin on human subjects and when might her research develop into a hair cloning treatment that is available to the general public?
A: It is very difficult to determine when this phase of the research might begin and it is even harder to predict when treatment might become available. First, the technology is not quite there. Dr. Christiano showed in her recent paper that changing the environment of skin (fibroblast) cells so that they could form into 3-D cultures enabled them to induce human hair-follicle growth. Although this was a major step towards cloning hair, additional work needs to be done before we will be able to mass produce fully-functioning human hair follicles to the extent needed for hair transplantation.
In addition, research on human subjects requires that experiments meet rigorous federal regulatory standards and these take time to be approved and carried out. Supposing that further study of follicle neogenesis results in a breakthrough treatment for hair loss, this treatment would still require meeting substantial efficacy and safety requirements of the FDA before it would be made available to the public. We will be communicating important developments as they occur through our Hair Cloning Research section and through periodic updates in the Bernstein Medical Newsletter.
- Read about Dr. Christiano’s Columbia University Study
- More in Hair Cloning Research
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Q: I haven’t seen much new with ACell. Have you been making progress with your research?
A: Thus far, we have not been able to multiply transplanted hairs with ACell, nor have been able minimize the width of the donor scars following FUT. At present, we are not recommending ACell to our patients, but are continuing to explore different ways of using it.
Q: Like many people who are eagerly awaiting hair cloning, I read about ACell’s new technology, but what is an “extracellular matrix”? — S.B., Chicago, IL
A: An extracellular matrix, or ECM, is the substance between the cells in all animal tissues. It provides support to the cells and a number of other important functions. ECM is made up of fibrous proteins that form a web or mesh filled with a substance called glycosaminoglycans (GAG). One type of GAG, called hyaluronic acid, functions to hold water in the tissues. Another important part of the extracellular matrix is the basement membrane on which the epithelial cells of the skin and other tissues lie. Elastin in the ECM allows blood vessels, skin, and other tissues to stretch.
ECM has many functions including providing support for cells, regulating intercellular communication, and providing growth factors for wound healing and tissue regeneration.
Read more about ACell’s MatriStem ECM on our ACell for Hair Cloning page.
Q: What are the possible obstacles that you see with hair cloning using the plucking technique? — D.E., Boston, MA
A: Plucked hair does not contain that much epithelial tissue, so we do not yet know what the success of the procedure will be. Plucked hairs will most likely grow into individual hair follicles that are not follicular units and therefore, will not have completely the natural (full) look of two and three hair grafts. This limitation may be circumvented, however, by placing several hairs in one recipient site. It is possible that the sebaceous gland may not fully develop, so the cloned hair may not have the full luster of a transplanted hair.
The most important concern is that, since the follicle is made, in part, by recipient cells that may be androgen sensitive, the plucked hair derived follicles may not be permanent. It is possible, that since all the components of a normal hair may not be present, the cloned hair may only survive for one hair cycle.
Since the ACell extracellular matrix is derived from porcine (pig) tissue, the procedure may not be appropriate if you are Kosher or allergic to pork. Of course, we do not know what other obstacles may arise since this technique is so new –- or even if the ones mentioned above will really be obstacles at all -– only time will tell.
Q: I heard that there have been some new advances in hair cloning and that it may be available sooner than we thought. I was planning on doing a hair transplant soon. Considering that hair cloning may be available at some point in the future, should I do FUE or FUT, or wait for cloning? — K.R., Fort Lee, NJ
A: Although there has been a major development in hair cloning with the use of ACell, an extracellular matrix to simulate hair growth, the model, at this point, is still in its earliest stages of development. It is hard to know when the technology will reach a state where it can be useful in hair restoration.
With respect to which you should do FUE or FUT if, theoretically, cloning is around the corner, the answer would be FUT, since FUT will give you the fuller look.
If the goal is to eliminate any trace of the traditional hair transplant, again FUT will most likely be the best choice, since the single linear scar would be easy to camouflage with cloned hair. With FUE, this would be much more difficult, since there are literally thousands of tiny scars. However, neither FUE nor FUT will preclude a patient from fully benefiting from cloning if, and when, it becomes available.
Q: I’ve read about some recent advances in hair cloning techniques with ACell. How does this work? — C.A., Stamford, CT
A: We, and several other groups, are engaged in studies using ACell MatriStem, a porcine extracellular matrix (ECM), to induce hair follicles to multiply in the patient’s own scalp (in vivo). This process differs from what people normally think of when speaking about cloning, namely producing populations of genetically identical cells, organs, or even individuals, in a test tube (in vitro).
In the current studies, a part of a hair follicle is implanted into the scalp in an extracellular matrix (ACell MatriStem), with the goal of inducing a complete follicle to form.
The concept is that if a small enough part of the donor follicle is removed, it will completely regenerate. Then, ACell MatriStem will induce the new hair fragment, implanted into the recipient site on the top of the scalp, to produce a new follicle –- thus we get two hairs from one. In one model being tested, hair is literally plucked from the scalp carrying with it enough genetic tissue to grow a new hair.
Q: I just read a press release saying that researchers have developed a successful technique to clone hair by using a wound healing powder. To paraphrase, the press release says:
MatriStem MicroMatrix, a product of regenerative medicine, ACell, Inc., is a wound healing powder that promotes healing and tissue growth and has now proven to help regenerate hair in the donor and recipient regions of hair transplant patients. While intended to heal ulcers and burns, Gary Hitzig, M.D. and Jerry Cooley, M.D., have found that its properties offer a broader scope of treatment, including hair cloning. “We’ve made amazing breakthroughs using MatriStem as a hair cloning tool,” said Dr. Hitzig. “We’ve been able to multiply the number of hair follicles growing in the recipient area, and as an added benefit are seeing faster hair growth. This new hair cloning technique also makes hair transplantation surgery less invasive.”
Is this new technique really a breakthrough in hair cloning? And if so, when can we start cloning hair?
A: It appears from preliminary studies that plucked hairs stimulated by ACell are in some cases able to regenerate new hair. Because the hair is placed into the recipient area and is partially derived from cells in the dermis, it is not yet clear whether the hair will be effected by androgens over time or if it will continue to bald.
The research so far is promising and a number of doctors are doing research in this area, including Dr. Schweiger and myself at Bernstein Medical – Center for Hair Restoration.
Q: I heard about the Lgr5 gene being a breakthrough in hair cloning. What’s the latest on that?
A: Many scientists feel that adult stem cells house the answer to cloning (regeneration) of hair follicles. One of the problems of hair cloning, however, is that the cells, once duplicated, “forget” that they are hair follicle cells.
It has recently been discovered that the Lgr5 gene, located in stem cells, appears to contain the “global marker” present in all adult hair follicles. If Lgr5 gene is the “calling card” of the cell, it may carry the cell lineage and shoulder the responsibility of signaling to surrounding stem cells what they are actually supposed to do as they multiply.
Recent experiments have shown that these Lgr5 cells maintain the cells ability to differentiate as hair follicles after many generations of being multiplied in the test tube and, therefore, have the potential of serving as the building blocks of entire new hair follicles. The successful exploitation of this gene would eliminate a major barrier to cloning hair.
Haegebarth A, Clevers H: Wnt signaling, lgr5, and stem cells in the intestine and skin. Am J Pathol. 2009 Mar; 174(3):715-21.
For more on how hair cloning works, visit our page on hair cloning and multiplication.
Q: What is the major obstacle to hair cloning?
A: Although many problems remain, the main one is to keep cloned cells differentiated (the ability to perform a specialized function, like producing a hair). There are certain cells in the skin, called fibroblasts, which reside around the base of the hair follicle. These cells are readily multiplied in a Petri dish. When these cells are injected into the skin, they have the ability to induce a hair to form (they are differentiated). The problem is that when these cells are multiplied in culture, they tend to lose this ability (they become undifferentiated).
A number of methods are being examined to keep these cells differentiated. Among them is the insertion of new genes into the cell’s nucleus to alter the expression of the existing genes. Another method is to change the spatial relationship of multiplying cells. The idea behind the second technique is that all embryonic cells have the same basic genetic material, but grow to have different functions (i.e., grow to form muscle, bone or nerves). One reason is that that the cells have a different physical relationship to one another and thus send different signals to each other based on this relationship. For example, the cells on the outside of a growing ball of cells may act differently than the cells on the inside, etc. If researchers can influence the way cells orient themselves as they multiply in the lab, this may enable them to become differentiated to produce hair and stay that way as the multiplication process continues.
Q: If someone were to get a hair transplant now, and then in the future when hair cloning becomes a possibility, would the hair transplant grafts be affected by hairs from the hair cloning procedure?
A: Cloned hair should not be affected by hair that is transplanted the traditional way and visa versa. If you have a hair transplant now, the hair restoration surgeon can add more hair in the future when cloning becomes available.
Q: Considering cell cultivation is made possible how could their injection create a normal formation of hair on the scalp and can they induce hair growth also in scarred areas where previously hair stopped growing?
A: That is the question. It is not known if these induced follicles will resemble normal hairs, and be cosmetically acceptable on their own, or if they will grow unruly and must be used as a filler behind more aesthetically pleasing transplanted hair.
Hair growth is an interaction between the dermal components (fibroblasts in the dermal sheath and dermal papillae) and the epidermal structures.
It is possible that the injected dermal fibroblasts will interact with resident epithelial cells to produce a properly oriented hair. A tunnel of epithelial cells can also be created to facilitate this process and some researchers are using cultures of both dermal and epithelial cells.
As you suggest, part of the challenge is not just to multiply the hair but to find a way for the hair to grow in its proper orientation. With scar tissue, the task will obviously be much more difficult.
Another issue is that the induced follicles are just that, they are single hair follicles rather than complete follicular units. Because of this they wouldn’t have the cosmetic elegance of one’s own natural hair, unlike that which is possible in follicular unit hair transplantation.
That said, much work still needs to be done and it is not clear at this time what might be the solution.
Q: I was reading the hair cloning area on your site and came across this passage:
“Donor cells can be transferred from one person to another without being rejected. Since repeat hair implantations did not provoke the typical rejection responses, even though the donor was of the opposite sex and had a significantly different genetic profile, this indicates that the dermal sheath cells have a special immune status and that the lower hair follicle is one of the body’s ‘immune privileged’ sites.”
Does this mean that I could get a hair transplant from someone else’s head of hair one day? Any type of hair?
A: Yes, in theory we will be able to use someone else’s donor tissue to clone hair – but the technology to actually do this is still years away.
Q: What are the major obstacles for scientists to cloning hair?
A: The main problem is that the cultured cells may lose their phenotype with multiple passages, i.e. lose their ability to differentiate into hair follicles after they have been multiplied.
Another problem of hair cloning is that the orientation of hair direction must be controlled. With mouse experiments, the hairs grow at all different directions. Scientists need to find a way to align the hair so that it grows in the right direction. Hair, of course, must also be of a quality that is cosmetically acceptable and matches the patient existing hair. And the hair should grow in follicular units. Individual hairs will not give the fullness or natural look of follicular units.
Another problem is the issue of safety. Are we sure that cultured cells may not turn into something else – such as malignancy cells with uncontrolled growth?
Finally, FDA approval would be required and this takes time. It is true that you do not need FDA approval for using your own hair, such as a hair transplant; however, when you take cells from the body and manipulate it in the lab, this requires FDA approval.
Q: What is the difference between hair cloning, hair multiplication, and follicular neogeneis? I have read about these terms on the internet and am completely confused.
A: Cloning generally refers to the multiplication of fetal stem cells or embryonic tissues. “Hair cloning”, as the term is generally used, involves the multiplication of adult tissue cells that are used to induce the formation of new hair, so the term is not exactly accurate.
“Hair multiplication” refers to the multiplication of adult hair structures. This model is not actively being pursued since the hair follicle is too complex to be simply cultured in a tube. Instead individual cells called fibroblasts are removed from the scalp multiplied in tissue culture and then these are injected back into the scalp in the hope that they will induce intact follicles to form.
“Follicular neogeneis” is probably the best of these terms, as it describes the formation of new follicles derived from inducer cells that are cultured and then injected into the scalp. It is the preferred term of Ken Washenik at Aderans. Interctyex uses the term “follicular cell regeneration” for its technology.
Q: I know that both Aderans and Intercytex are doing research with cloning hair. Is there any difference in their approaches?
A: Aderans is using the “two-cell” approach. They feel that the best way to produce viable hair follicles is to use a combination of inducer cells and responder cells. Each would be multiplied separately and then injected together into the skin. The inducer cells are follicular fibroblasts and lie at the base of the hair follicle. The responder cells are keratinocytes. They feel that the combination of cells will have the best chance of producing clinically useful hair.
Intercytex prefers a one-cell approach. Their researchers feel that when the cultured inducer fibroblasts are injected into the skin there will be enough existing cells in the skin to produce a cosmetically viable hair. In their experimentation, Intercytex uses a new animal model, termed the “flap graft” model, that involves the implantation of cultured dermal papilla cells with keratinocytes placed under a flap on the back of hairless mice. Later the flap is exteriorized (turned over), allowing the hair to grow normally. Exactly how this will be applied to clinical use in humans is not clear.
A completely different view is held Dr. Ralf Paus at the University of Luebeck in Germany. He feels that there are already enough stem cells in the bald scalp and that the key to hair re-growth is to target key elements in the hair cycle. He feels that topically applied inhibitors of catagen (the resting phase of the hair cycle), exogen (the formation of an empty hair follicle), or inhibitors of the terminal-to-vellus transformation (the process of a hair shrinking in size under the influence of DHT and referred to as miniaturization) will the most effective way to go.
Finasteride and dutasteride are drugs that work in this way, but are clearly not very effective in stimulating new growth. He also feels that an anagen inducer, along the lines of a minoxidil-type medication has a better chance of success then the stem cell targeting strategies described above. In these cases one would, in a sense, rejuvenate dormant hair follicles rather than induce new ones to grow.
Q: I have heard that Dr. Jahoda was able to clone hair. Is that true? — M.T., Cincinnati, OH
A: Possibly the most interesting work related to cloning hair was done by Colon Jahoda in England over a decade ago. Dr. Jahoda’s work is significant because he identified an inducer cell — i.e. fibroblasts in the outer portion of the hair follicle (the outer root sheath) — that can stimulate the skin to produce new hair. It is well known that fibroblasts, unlike many other tissue cells, are relatively easy to culture.
Theoretically, a patient’s fibroblasts could be removed from the sheaths of just a few follicles and then cultured to produce thousands of follicles. These fibroblasts could then be injected back into the scalp to induce thousands of new hair follicles to grow.
In the study, fibroblasts from a man were injected into the forearm of genetically unrelated women. The cross-gender aspect of his experiment has received much publicity and is potentially of great importance to burn victims, but has little relevance to hair transplantation for male pattern baldness. Patients would probably benefit most from using their own cultured fibroblasts for the best match.
So far this important single study has not been reproduced.
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