Two clinical trials since 2002 using transplanted adult stem cells successfully led to tissue regrowth in damaged hearts, but 11 of 18 patients later developed potentially fatal heart rhythm disturbances, including one who required cardiac resuscitation. "It was a potential case of the cure being worse than the disease," says senior researcher and cardiovascular physiologist Eduardo Marbn, M.D., Ph.D., professor and chief of cardiology at The Johns Hopkins University School of Medicine and its Heart Institute. "It was very discouraging to know that these patients developed arrhythmias, yet not know if it was the muscle stem cells at fault or simply a progression of the patients' heart disease."
Marbn is also editor in chief of the journal Circulation Research, in which the findings will be published online June 23.
Marbn's team says it has discovered the source of the arrhythmias to be transplantation of myoblasts, which are adult stem cells taken from patients' own healthy skeletal muscle. In patients, these myoblasts are injected directly into damaged heart muscle to regrow new tissue. In petri dish studies using these cells, the transplantation process caused an immediate disruption in heart muscle tissue's regular electrical rhythm, or conductivity, which is necessary to stimulate a regular heart beat.
Moreover, the Hopkins group was able to minimize arrhythmias dramatically by using gene therapy to replace a key protein, called connexin 43, missing in heart muscle fibers that regrew as a result of the stem cell injections. Connexin 43 makes up the gap junctions between muscle cells, allowing cells to communicate with each other to regularly contract and expand.