Hair Cloning Obstacles - Bernstein Medical - Center for Hair Restoration
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New research published in the journal PLoS One found that embryonic stem cells can be used to form a type of cell that induces new hair follicle growth, and that these cells promote robust hair growth when implanted into mice.

Background

Dermal Papilla (DP) cells play a role in new hair follicle formation and in the growth of new hair. Because of this role, it was hoped that DP cells grown in the laboratory (i.e., grown in culture) could form the basis of a treatment for genetic hair loss. However, it turned out that these cultured DP cells lost their hair follicle-inducing potential too quickly to be useful in treating hair loss.

New Research

Now, however, new research has found that human embryonic stem cells (hESCs) can generate cells that are functionally equivalent to DP cells. ((Gnedeva K, Vorotelyak E, Cimadamore F, Cattarossi G, Giusto E, Terskikh V.V, Terskikh A.V. Derivation of hair-inducing cell from human pluripotent stem cells. PLoS One. 2015 Jan 21;10(1)) Like DP cells, these functionally equivalent cells can induce hair follicle formation just as readily as DP cells. But more significantly, unlike cultured DP cells, they do not lose their potential to induce hair follicle formation when grown in the laboratory. This discovery represents an important advance in developing a hair cloning technique to cure pattern baldness.

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Dr. Claire Higgins and her colleague Dr. Colin Jahoda have published an overview of hair cloning and the challenges scientists face in attempting to develop hair regeneration therapies for androgenetic alopecia or common balding. The article, published in Hair Transplant Forum International, points to two central problems in developing a hair loss therapy. The first is the difficulty in getting dermal papilla cells in humans to self-aggregate and form hair follicles and the second is the inability, thus far, of scientists to generate normal hairs and follicles.

Higgins and Jahoda describe how it has been known for decades, through the work of Lille and Wang and others, that rat dermal papillae self-organize into new hair-producing follicles when they are injected or grafted into the skin. Human dermal papilla cells, on the other hand, have never exhibited what they call the “aggregation phenomena,” and instead they disperse in the skin in what appears to be a wound healing mechanism. In fact, human papillae, when grown in a laboratory culture, can act as “mesenchymal stem cells” and differentiate into a variety of cell types.

While multiple efforts to induce dermal papillae to form new hair follicles have failed, the research that Higgins and Jahoda have published on hair follicle neogenesis has resulted in a new technique to do just that. The success of the 3-D culturing of dermal papillae to induce hair follicle neogenesis was a breakthrough in that the scientists have found a way to improve the intercellular communication that is essential to inducing follicle growth.

Having made significant progress in improving this vital communication link between dermal papillae cells, scientists still have to contend with a series of obstacles that stand in the way of a hair cloning therapy for human hair loss. One such problem is the quality of hairs that they have been able to grow using the hair follicle neogenesis technique. The hairs they have successfully produced have been small and have grown in non-uniform direction. Another unanswered issue is how long the hair follicles will grow and whether or not they exhibit the cyclical hair follicle growth patterns of a typical human hair follicle. The ability to reproduce significant quantities of normal hair will continue to be the central focus of research going forward.

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Scientists from Durham University in the UK have shown for the first time that a lab technique, called a three-dimensional cell culture, can produce spherical structures that are similar to naturally occurring structures in hair follicle formation (called dermal papilla or DP). This breakthrough study by Claire Higgins and Colin Jahoda, published in the June 2010 issue of the journal Experimental Dermatology, ((Higgins C, Jahoda C, et al. Modelling the hair follicle dermal papilla using spheroid cell cultures. Experimental Dermatology 2010; 19: 546–548.)) has the potential to unlock the ability of researchers to develop functional DP cells which can be used in hair restoration techniques such as hair cloning or hair multiplication.

Background

Hair cloning techniques have been theorized for decades. The basic idea is:

  1. a physician takes a sample of skin cells from a patient
  2. dermal papilla cells are extracted
  3. the DP cells are cloned (multiplied) in a laboratory culture (i.e., a petri dish)
  4. the cell formation is then injected back into the patient’s balding scalp where it produces permanent hair that continues to grow

The first three steps are a piece of cake. But that is when the strategy breaks down. When DP cells are grown in a petri dish they exhibit some of the qualities of DP cells in the human body but not all, so injecting this aggregate into the skin fails to lead to hair follicle growth. Something was missing.

In 1991, Wobus, et al published a study in the journal Differentiation ((Wobus AM, Wallukat G, Hescheler J. Differentiation 1991: 48: 173–182.)) that described a new technique for researching cells that in nature exist as clumps or masses of cells. The idea was to suspend a group of cells under a flat surface so that gravity would pull the cells into a droplet. This “hanging drop” method yielded a three-dimensional culture that enabled the study of embryonic stem cells as well as the proteins they produce that allow for intercellular communication.

Having hit the wall with two-dimensional DP cultures, Higgins and Jahoda set out to try Wobus’ concept of using 3-D cultures to study DP cells.

The Study

Higgins and Jahoda harvested eight cell strains of human DP cells taken from scalp hair follicles. These eight strains were cultured in either 35-mm dishes or hanging drop cultures consisting of 3,000 cells each. The cultures were maintained between 30 and 72 hours, then collected and analyzed using immunofluorescence or transcriptional techniques.

Results

The DP cells grown in hanging drop, 3-D cultures exhibited behavior significantly akin to DP in human hair follicles. The 2-D cultures grown in the 35-mm dishes did not.

Conclusion

Without the ability to form functional dermal papilla aggregations, hair cloning was essentially at a dead end. In the 3-D configuration, the aggregated cells were able to communicate with one another and to continue to differentiate as hair follicles. By using Wobus’ 3-D hanging drop technique, Higgins and Jahoda may have unlocked the secret to forming these powerful, but elusive, structures that are critical to the hair growth cycle.

Following this study, more research needs to be performed to induce the spherical cells to initiate the growth of new hair follicles and to develop ways to ensure that the induced hair follicles are immune from the factors that cause genetic hair loss. Should those two riddles be solved, hair loss will have been effectively cured.

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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.

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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.

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