Barriers to Embryonic Stem Cell Treatments

Embryonic stem cells are widely touted as having the potential to cure serious diseases and heal devastating injuries. Embryonic stem cells are obtained initially by destroying embryos and, theoretically, can then be reproduced indefinitely. Embryonic stem cell therapies are currently not available to treat any human diseases or injuries. While research is ongoing and clinical trials are beginning, there are certain hurdles that have so far limited the potential of embryonic stem cells.

Any embryonic stem cells that may currently be used in a treatment have a different genetic makeup than the patient. Because they come from a genetically distinct donor, they are sometimes called heterologous stem cells or allogenic stem cells. The problem with heterologous stem cell transplants is the same as with any other heterologous tissue or organ transplant. The patient's immune system sees these genetically distinct cells as foreign and treats them as invaders. This phenomenon is called immune system rejection.

In organ transplants, immune system rejection requires the use of powerful anti-rejection drugs. Side effects of anti-rejection drugs can include high blood pressure, kidney and liver toxicity, and increased susceptibility to infection, depending on which drugs are used (Peters 2003). Treatments using transplants of heterologous stem cells would likely require the use of anti-rejection drugs, just as with organ transplants. In this case, the risks of the medications must be compared with the benefits of treatment.

The problems of immune system rejection can only be overcome in humans through the use of therapeutic cloning. Therapeutic cloning has so far not been successful in humans. In addition, bioethicists have raised significant ethical objections to human cloning which must be resolved.

Much of the current research on embryonic stem cells has been done on mice. In mice, researchers have the advantage of being able to use syngenic stem cells — that is, embryonic stem cells with the same genetic makeup as the host — due to the extensive selective breeding that has been done on laboratory mice.

With syngenic embryonic stem cells, researchers have had great difficulty causing the stem cells to differentiate properly. For example (Nussbaum 2007), in experimental heart disease treatment, the goal of the research is to cause the stem cells to become heart muscle cells, but doing this in vivo (that is, inside the body) has been challenging. Instead, the stem cells form masses of undifferentiated cells. These non-cancerous tumors are called teratomas. Even when placed in injured heart tissue, which hypothetically should give chemical cues to the stem cells to become heart muscle cells, the stem cells instead form teratomas. Research continues on how to solve this significant problem.

With allogenic embryonic stem cells, the teratomas are eliminated by the immune system and therefore do not cause problems. Unfortunately, they also do not help treat the disease they are intended to treat.

• Thomas Peters, M.D. "Transplant Drugs: Medicines That Prevent Rejection." aakpRENALIFE (newsletter) 2003 November;19:3.
• Jeannette Nussbaum, Elina Minami, Michael Laflamme, Jitka Virag, Carol Ware, Amanda Masino, Veronica Muskheli, Lil Pabon, Hans Reinecke, and Charles Murry. "Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response." The FASEB Journal (Journal of the Federation of American Societies for Experimental Biology) 2007;21:1345-1357.