Research involving embryonic stem cells, like that with adult stem cells, has experienced some exciting breakthroughs in the past decade. Some of the most important of these discoveries have been in the area of technique and methodology. In March 2005, for example, researchers at the University of California-San Diego (UCSD) School of Medicine reported that they had developed a method for maintaining embryonic stem cells in a proliferative state without the use of feeder cells. The UCSD scientists added a human protein called activin A to an embryonic stem cell line culture and found that the culture survived and divided as efficiently as it had using more traditional (usually murine) feeder layers. This result is important because the use of either nonhuman or human feeder cells introduces the possibility that proliferating embryonic stem cells may become contaminated by those feeder cells, making them useless for transplantation into a human subject.
Only months earlier, a second group of UCSD researchers had described another methodological development in the use of embryonic stem cells. They reported initial progress in coaxing such cells to differentiate along one or more lines of specialization into liver, adipose, nerve, skin, or some other type of mature cell. The news was important because the use of embryonic stem cells in regenerative medicine and other applications depends on just this ability of directing the differentiation of cells in some specific direction.
Researchers have also reported success in using embryonic stem cells to treat certain medical conditions and disorders, usually in experimental animals In January 2005, for instance, a research team at the University of Wisconsin–Madison’s Stem Cell Research Program headed by Su-Chun Zhang reported that they had coaxed human embryonic stem cells to become spinal motor neurons, nerve cells that control movement.73 This accomplishment is one of the first steps needed for using embryonic stem cells in transplantations to treat diseases of the nervous system, such as amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease).
In a study that represents a potential second step in such treatments, researchers led by Hans Keirstead at the University of California–Irvine’s Reeve-Irvine Research Center reported in May 2005 that they had treated rats with spinal cord injuries with human embryonic stem cells and observed significant improvement in the rats’ motor skills. Rats who had been injured up to seven days before treatment experienced nearly complete recovery after treatment with ES cells, although treatment was not effective with animals who had been injured many months prior to treatment. The principal investigator later said that “We’re very excited with these results. They underscore the great potential that stem cells have for treating human disease and injury.”
That level of enthusiasm is not uncommon among scientists working with embryonic stem cells. However, most researchers acknowledge that the bright hopes for using ES cells in regenerative medicine and other applications depends on solving a number of difficult technological problems. One of the most serious of those problems is the possibility that embryonic stem cells implanted into a patient may begin to proliferate and grow out of control, as happens during the development of an immature teratoma. Of course, scientists already know that such events have occurred in experimental animals following the implantation of embryonic stem cells, and the question remains as to how it can be prevented in humans during a therapeutic application. Uncontrolled growth of cells would result in the development of a cancer, which could be as or more serious a medical problem as the one being cured.
A second major problem relating to the use of embryonic stem cells is the possibility of rejection by a patient’s body. Any time cells, tissue, or organs are transplanted from one person to another person, the recipient’s body is likely to initiate an immune reaction against the implanted material. Cells in the transplanted material carry chemical markers on their surface that provide them with a unique identity. A recipient’s immune system is able to detect those markers and recognize that they do not come from its own body. It then initiates an autoimmune response that can cause serious damage to, and even kill, the patient. Again, the cure in such a case is worse than the disease being treated.
A third problem relates to maintaining control over the destination of stem cells implanted into a patient’s body. Suppose that scientists are able to find a way of coaxing embryonic stem cells into a particular type of specialized cell that is then injected into a patient to treat a disease. Can a scientist be certain that, once injected, those cells then travel to the appropriate place in the body (nerve cells to the nervous system; muscle cells to muscle tissue; skin cells to skin; and so on), or is it possible that they would migrate to inappropriate locations (nerve cells to muscle tissue or skin cells to the nervous system, for example)? Thus far, scientists have been unable to answer that question.
Technical problems like these may exist for adult stem cells also, but are likely to be less serious than they are for embryonic stem cells. The reason is that the very quality that makes embryonic stem cells desirable for so many medical applications their pluripotency also contributes to some of the problems that may be associated with their use in medical situations.
