Stem cell therapies to repair heart damage were one of the first to become widely available via medical tourism, and have been underway in earnest for more than a decade now. There is evidence from their use that benefits can be attained for patients. Providers and researchers continue to refine their techniques. There are numerous studies. That evidence is not good enough for the conservative end of the scientific community, who require a complete and rigorous understanding of the mechanisms of action before proceeding with enthusiasm, and nor for regulatory bodies in the US and Europe. Thus trials continue, now into their late stages, and treatments remain unavailable in many countries:
Like any new branch of medicine, cardiac cell therapy has progressed in fits and starts. Despite dozens of clinical trials, there's no slam-dunk treatment for improving the cardiac function of heart failure patients, but marginal, statistically significant improvements observed in some of the studies are propelling the cell-based therapies to ever larger, more expensive, and more rigorous trials. Most cardiologists remain underimpressed, says the head of an ongoing Phase 3 trial in Europe that involves injecting bone marrow cells into heart attack patients. "If [the trial] is positive, that's great, but I still think we'll have quite a challenge to convince people. If it's negative, then you get most of the cardiac community saying, 'Yep, we expected that.'?"
Now, it's make or break. Some anticipate that the results of the trial and two other ongoing Phase 3s will finally provide definitive evidence supporting the efficacy of cell therapies for the heart - evidence that has so far been lacking. On the other hand, negative results could spell the end of the approach altogether. "If our Phase 3 doesn't work, I think there's little likelihood any program could succeed in this indication," says the CEO of a Belgium-based firm sponsoring a clinical trial involving bone marrow-derived cells. "In the event they don't work [this time], I think it will be the end."
The idea to pluck cells from a person's bone marrow and shoot them into the heart took root in 2001, when researchers showed that doing so in mice could help regenerate damaged heart tissue. Yet no one knew how the cells worked. At the time, the prevailing thought was that stem cells took up residence in the heart and proliferated to produce new tissue. But this idea has since become a matter of debate. While some researchers claim the cells can form new cardiac muscle, others assert that the cells only very rarely differentiate into cardiomyocytes and instead support cardiac regeneration by other means.
Many scientists now believe that the introduced cells perform a paracrine function, signaling the activation of reparative pathways via growth factors or other secreted messengers. On its own, the heart regenerates about one percent of its tissue per year via the division of cardiomyocytes; perhaps cell therapies simply boost that normal behavior. The absence of a concrete mechanism of action has been one of the main criticisms of the field. On the other hand, most patients don't care how a treatment works, just that it does. "We have more trials than we have meaningful basic science papers. You'd like it to be the other way round. But I understand why there was an explosion [of clinical trials] - because there is such a need." And many researchers disagree that a known mechanism is required for advancing the therapy. "Nothing moves a field forward like actual clinical trials." While mechanisms are important - knowing them can help optimize treatments, for instance - "you can't slow things down because the mechanism of action isn't agreed upon by everybody."