UPDATE ON CLONING
The hope and dream of every man or woman afflicted by hair loss is for a simple, easy treatment that can restore all of the scalp hair with a minimum of invasive intervention. This is the also goal of dermatologists, both those who practice hair restoration surgery and those who do not. For the past 10 years or so there has been much made in the media of efforts along these lines using "cloning" of stem cells for hair restoration. This is a look at the status of cloning.
There are two companies with laboratories in the United States doing ongoing research in the cloning approach to hair restoration. They are Intercytex, headquartered in the UK and Aderans Research of Japan. Intercytex has published results of the studies done in human beings. This is an extremely small number, around 35 patients. Aderans has revealed their studies done in experimental animals.
The general approach in cloning is to remove what are believed to be stem cells from healthy human follicles. The cells are then multiplied in the laboratory in specialized media. This is called tissue culture multiplication. Many new stem cells are available to be injected back into the scalp to produce new hair follicles or perhaps stimulate old stem cells to become active again.
The current state of knowledge is that there are likely two populations of stem cells responsible for producing a hair follicle. One component comes from the outermost layer of skin, the epidermis; the other is found in the lower layer of skin or dermis. The epidermal component is located in the region at the attachment of the muscle that causes hairs to stand up (arrector pili muscle) and where the oil gland enters into the follicle. This is located high on the hair follicle just under the epidermis or outer layer of skin. This is called the bulge area. A dermal component is located deep in the lower layer of skin at the bottom of the follicle. It is a collection of cells called the dermal papilla.
The diagram above illustrates these two areas. One approach the researchers use is to extract the cells from the bulge and/or the dermal papilla of growing hairs. Then they multiply one or the other in tissue cultures and reinject them into bald areas or near hair follicles to create new hairs. Another way of doing this is to mix the two populations of stem cells together in the tissue cultures and and produce primative follicle like structures. These "proto hairs" can then be injected into bald scalp..
Intercytex has shown in their small series of human studies some increases in hair counts in the injected areas when the dermal papilla cells had been injected along with growth factors. We don’t know anything about the quality of the hair.
Aderans has published their experiments using experimental mice that do not have immune systems. Immunoincompetent or “nude” mice are used so that the injected cells are not rejected. In these published studies they have shown something like a hair growing from mixed combinations of stem cells injected into the mice.
It is likely that these companies are farther along in their research then they have revealed in published studies. Still, hair with natural luster, sheen, perfect direction, and synchronized growth has not even been hinted at as yet. So far in studies revealed by these companies and others who are spending millions and millions of dollars on coming up with a hair loss cure would indicate that a safe, inexpensive, available product for use in humans is some years off.
For an alternative to cloning see the next article.
REGENERATION VERSUS CLONING
Most of the media buzz about modern advances in hair restoration is all about cloning. Cloning of hair follicle stem cells is hoped to produce a new head of hair for people with balding or thinning hair, both men and women.
There is another approach. Right now there are two products repeatedly proven to regenerate hair follicles. These are Rogaine (minoxidil) and Propecia (finasteride); these two products are FDA approved in the United States for treatment of hair loss. Both are able, albeit by different mechanisms, to regenerate or invigorate weak follicles. The only problem is that neither of these, nor even both of them together, will grow hair of any significance on a totally bald scalp. They just don't work well enough. Still, these are two products that work by regenerating weakened or resting hair follicles. They work not only in genetic alopecia but other causes of hair loss as well such as iron deficiency and thyroid induced hair loss.
The general approach with stem cells is described as removing stem cells, cloning them and somehow putting them back into the scalp to grow hair. We really don't have anything in the hair restoration field that works this way. While most attention is paid to the cloning approach, there is a school of thought that suggests that regeneration of dormant follicles may be a better way to go.
For example, injecting steroids into areas of alopecia areata, a scalp disease, will cause totally bald areas to re-grow hair. Unfortunately, steroids do not work in much more common genetic hair loss. The key finding here, however, is that follicles that are turned off by processes that we really don't completely understand as yet, can be turned back on. In genetic hair loss it works with Rogaine, it works with Propecia, not as well as we would like, but it works. In alopecia areata it works with steroids.
We must ask the question then, why shouldn’t we reactivate dormant stem cells that are already present? Why must we remove healthy stem cells from the scalp, process them, and then inject them back into other areas of the scalp again? Why not just activate the stem cells that are already there? The pro-cloning argument is that the stem cells are gone in bald scalp.
While there remains controversy about this, research indicates that these stem cells are present, even in a totally bald scalp. The hair follicle may have become invisible, but there is evidence that the stem cells are still present. The alternate approach is to find the biochemical messengers that will cause the turned off follicles to reform by switching on dormant stem cells that are still in the scalp in bald areas.
I favor the theory that the stem cells are still present in balding scalp, at least for a while. I have seen new hair grow in thinned areas with the use of Propecia and Rogaine. This is supported by numerous studies.
There are potential major problems with cloning. The stem cells after all the processing outside the body could go awry and turn into something undesirable, maybe a painful cyst, or worse a skin cancer. A big road block to cloning is to not just produce hairs, but ones with youthful, full pigmentation, sheen, body, and orientation on the scalp.(This can be done with traditional hair transplantation.)
The pro-regeneration camp suggests that the cloning approach is like buying the house next to you because your door is broken. They suggest fixing your own door instead. Research needs to continue with both approaches.
IS IT REALLY YOUR MOTHER'S FAULT AFTER ALL?
Recently a genetic test for hair loss has been developed and marketed. This test looks for different versions of a gene called the “AR gene” located on the X Chromosome. AR stands for androgen receptor. This is one of the genes that determine whether a person will have hair loss.
Based on information from 100 years ago, there was a belief that hair loss came from a person’s mother’s family. Observations did not bear this out. Lots of men had baldness whose mother’s family history did not show hair loss. So this concept of “from the mother” was viewed with some skepticism in the medical world.
As we have learned more about genetics we now understand the concept of multi-factorial inheritance or multiple different genes, possibly on many different chromosomes, being responsible for an individual’s final phenotype which is a genetic term for the entire makeup of that person. Things making up a phenotype include: how tall, eye color, male or female, disease susceptibility or resistance, skin color, some physical and mental abilities, and many, many other characteristics, including susceptibility to hair loss. These are what make each person unique.
Some human characteristics are determined by a single gene. Blue eyes versus brown eyes, is a good example. Other characteristics have a polygenic inheritance. This means the final phenotype is determined by the interaction of multiple genes and usually environmental factors.
This genetic test is sold by a company called Hairdx. It has some value for young people who have not yet experienced hair loss but have a family history for hair loss. They can have a mouth swab and find out if they have the version of the AR gene on their X Chromosome that promotes or may diminish their future tendency for hair loss.
For a person with hair loss already this information is probably of less value. What is most interesting is the presence of this gene on the X Chromosome. This part of one’s genetic material always comes from the maternal family line. Men (genetically X-Y) have only one X chromosome always get their X Chromosome from their mother. Women (genetically X-X) who have two X Chromosome get one from their mother and the other from their father’s mother.
While many genes, still to be elucidated, in addition to the AR gene determine hair loss, This one gene on the X Chromosome does support the idea that hair loss, at least in part comes from the mother’s family. So in hair restoration like many other areas of science an old idea, previously dismissed, has gained credence once more.
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