Monday, April 14, 2008

promise of stem cells

Much of the promise of stem cells rests on a scheme for replacing parts worn out by age, injury, or infirmity. Unfortunately, the reality of stem cell biology is overshadowed by the hype. For example, the future is imagined to hold an inexhaustible source of stem cells with a perfect genetic match banked at a local hospital, available for your every medical whim. Need a new pancreas? Place your order, and three weeks later a new one lies ready and waiting in the surgical suite. Heart failure? No worries -- a few injections with multipotent stem cells will grow new cardiac tissue. And thus may 21st century patients extend their lives -- through a kind of patchwork medicine, held together by a fabulous, potent cell. This future sounds incredibly exciting. But it will take time -- and vision -- to us get there.

The truth of the matter is, we've got a goodly distance to go before regenerative medicine -- a catchall term for stem cell therapy -- will help large numbers of patients. It is very possible that many diseases will have to wait for cures from other quarters of medicine. Before any medical treatment (including cell and tissue transplants) is made available through hospitals or clinics, it must first be tested in humans through tightly regulated phases of clinical trials. The first phase determines safety and side effects in a few dozen subjects; the second phase tests efficacy in hundreds of patients; the third and subsequent phases try to prove statistical significance and confirm its effects in many hundreds or thousands of patients. The U.S. Food and Drug Administration (FDA) evaluates the data, and if the results pass muster, the product is approved for sale and moves to the market. Developing a new therapy goes slowly and is terribly expensive -- discovering, testing, and manufacturing one new drug can take between 10 and 15 years and cost nearly a billion dollars.

A hypothetical timeline of a new treatment for skin transplants might look like this:

• Basic Research: In 2006, a source of powerful adult stem cells is discovered beneath human skin. The rare cells are fingerprinted by genetic markers, and the markers are used to isolate the cells from the body and culture them in the lab. Over the next two years, technology is developed to grow the cells in quantity and used to change them into a variety of skin cell types.

• Preclinical Research: Different lines of skin stem cells and their progenitors are transplanted into the injured skin of a transgenic mouse with no immune system (to prevent rejection of the human cells). Over time the transplants are observed. One line works: the cells survive, go to the site of the injury, integrate into the skin, and heal the wound. Other kinds of animals are similarly tested. The tests take three years to complete.

• Clinical Research: The encouraging results in animals prompt tests in humans. In patients with severe burns, the patient's own skin stem cells are cultured, multiplied and then transplanted at the wound site. The cells improve blood flow, promote healing, and reduce scarring. Using adult stem cells is not the only way to approach the problem. An hESC line using nuclear transfer might also produce the skin stem cell in question. The technologies are further developed by companies, tested in more humans, and manufactured for use for burn victims. In 2014, the FDA approves the first cell therapy for use in clinics.

If the treatment being studied is for a disease with a genetic cause, another wrinkle must be ironed out. The faulty gene has to be corrected before the cells are reintroduced or the transplant could succumb with time, as did the original cells. This presents an added set of challenges to stem cell transplants. Once a genetically engineered stem cell is placed into the body and grafts into an organ, it may be there for life. If the change is in one of the wide-ranging cells of the blood or nervous system, the proteins made by the new gene will be everywhere in the body. Care must be taken to limit the effects of the therapy only to the affected areas.

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