Stem Cell Research and Hair
Stem cell research is very much in the news these days. Most of the news and controversy is about embryonic stem cells. These are the cells found in the very earliest stage of the embryo (30 - 150 cells) before it becomes implanted in the uterine wall. Scientists believe that these cells are pluripotent. They are able to give rise to all the specialized cells and tissues of the body.
The information generated from this research has positive implications for people who are losing their hair. This research will also give hope to people with less urgent problems like terminal cancer, Alzheimer's disease, Parkinson's disease, and spinal cord injury.
The stem cell research that will be most relevant to people with hair loss, however, does not involve embryonic stem cells. It involves the adult stem cells - namely, those adult stem cells in the bulge area of the hair follicle.
Here's a simplified description of how these bulge stem cells reconstitute the hair follicle in the late telogen and early anagen stages of the hair cycle. During the short catagen stage of the cycle when the lower segment of the hair follicle rapidly shrinks, the dermal papilla climbs or is pulled to a point just below the bulge area. While in this area during the subsequent telogen stage, the dermal papilla gives out complex chemical signals that the bulge stem cells receive. These signals seem to indicate to the bulge stem cells that it is time to divide. These stem cells then produce exact copies of themselves, but they also produce what are called progenitor cells. These progenitor cells develop into mature, specialized (differentiated) cells.
What characterizes an adult stem cell is its ability to make exact copies of itself (self-renewal) and to generate these progenitor cells which eventually divide and become specialized cells - in this case, the specialized cells of the hair shaft, the inner root sheath, and the outer root sheath.
Here is the current theory in some detail of what happens when the dermal papilla sends out these complex chemical signals to the bulge area stem cells. First, the stem cells and their progenitor cells migrate down the outer root sheath or possibly down the basement membrane, the thin membrane that bounds the outer root sheath. Second, when these cells reach the matrix they start to divide profusely and to make their final (terminal) differentiation into the layers that form the structure of the follicle. And third, some of the cells also migrate up from the bulge and become part of the skin surface, the epidermis.
Before the stem cells leave the bulge area in their migration to the areas where they are needed, they are uncommitted - their fate is not yet known. They stay uncommitted till they get signals either from the dermal papilla or from some other source, possibly the matrix or epidermal cells. When they get these chemical signals they usually generate an intermediate state - the progenitor cells - before they divide into the completely specialized cells of the various hair follicle tissues or epidermal tissues.
The challenge now for scientists is to find out how these chemical signals work, how they initiate the migration of stem cells and progenitor cells to areas where they are needed, and how these cells are ultimately differentiated into the specialized cells of the six layers of the hair follicle.
There are several theories about why the bulge stem cells switch on to form the specialized layers of the follicle. One theory is that the signaling molecules of the papilla instruct the stem cells to divide and migrate - to home in on - where they are needed. A good, but highly technical, article on these signaling molecules is in the June 2001 Scientific American.
Another theory is that nearness to injury or to dying cells causes stem cells and progenitor cells to home in on the areas where cells are needed to repair damage. Cell death (apoptosis) especially seems to be a powerful stimulus initiating stem cell division and migration.
Much research is now being done on both the embryonic stem cells and the adult stem cells. It was only a few years ago when two teams of scientists were able to isolate stem cells and grow identical (clonogenic) copies of them in the laboratory. Intense research is now being done on these cell lines in a half dozen countries around the world.
Many scientists predict that in the near future the understanding of the chemical signals between the dermal papilla and stem cells may enable dermatologists to (1) alter the cycling of hair follicles, (2) "revive" dormant follicles, and (3) coax miniaturized vellus follicles into terminal follicles. There is also the small possibility for some drawbacks, one of which is tumor formation. Because stem cells are slow cycling they are susceptible to mutation and therefore to malignancy.
But in the scientific community there is much optimism about the new research into stem cells and the ability of this research to generate real help for people with hair loss problems. Elaine Fuchs, a molecular biologist at the University of Chicago, writes:
The ultimate goal for molecular medicine is to channel multipotent human cells with high proliferative capacity into specified differentiation programs within the body. If this becomes possible...and all indications are that it will, a multitude of therapeutic uses can be envisioned. Among these are...the generation of dermal papilla or hair follicle stem cells for treatment of certain types of baldness. - Cell, January 7, 2000
It looks like scientific knowledge has progressed quite a bit since that dermatologist in ancient Egypt recommended his mixture of crocodile fat and hippopotamus dung for hair loss.
Stem Cell Research, an Update
Here's the straightforward process that people suffering from hair loss would like to see. It may be closer than even they could optimistically hope for.
- Stem cells (uncommitted cells, "blank slate" cells) are removed from a person's good hair follicles from the sides or back of the head.
- These stem cells are then seeded (implanted) into bald or thinning areas of scalp tissue in which they start to proliferate and form new hair follicles.
- After a period of time these hair follicles produce thick, pigmented hair that grows at the proper angle.
- This new hair lasts - and there are no complications, no side effects.
Dr. George Cotsarelis and his team of researchers at the University of Pennsylvania might have brought this scenario closer to realization according to an article published on a website - www.nature.com - on March 14, 2004. (If you want to read the article on this website, it'll cost you $30.) This same article will be published in the journal Nature Biotechnology in April.
The Cotsarelis team was able to isolate certain stem cells in the hair follicles of mice. These stem cells were in an area of the follicle called the bulge. They were able to separate these cells from the surrounding tissue by getting them to produce a green fluorescent glow. The other cells in the area did not glow. A cell sorting machine was then able to separate the glowing cells (the stem cells) from the non-glowing cells.
Dr. Cotsarelis and his team now transplanted some of these stem cells into the skin of specially bred bald mice. These cells after a period of time proliferated into hair follicles, adjacent sebaceous glands, and some skin cells. In human beings, however, going from a stem cell into an organ (hair follicles are micro-organs) may take a lot of biochemical prodding. Dr. Cotsarelis thinks it may take ten years before results similar to the ones obtained in mice are obtained in humans.
The research by Dr. Cotsarelis and his team might generate other breakthroughs also. These "purified" stem cells that were isolated will be able to help researchers find which genes are switched on when a hair follicle forms or perhaps miniaturizes. Gene chips will be used in this new research. Gene chips are small devices (the size of a postage stamp) with a glass substrate wafer. They contain a large number of cells - perhaps a half million. Each holds DNA from a different gene. Many sophisticated genetic tests can be performed with this mini-machine. Dr. Cotsarelis believes that with the data emerging from this new technology it will be possible to find better, more effective drugs to reverse the balding process. All this may happen - the new drugs, that is - in the next five years.