Reports on stem cell therapies for post-heart attack tissue repair have described at best modest success. Most clinical trials have used bone marrow-derived cells, which are thought to promote the growth of new blood vessels in the damaged heart, but many of these studies have shown no benefit for the patient. A better alternative may be to use heart muscle cells (cardiomyocytes) or progenitor cells that can form both heart muscle and blood vessels for cell therapy. These can both be derived from human embryonic stem cells.
In a paper published October 22 in Stem Cell Reports, the journal of the International Society for Stem Cell Research, a study was described in which the authors compared how well human embryonic stem-cell derived cardiomyocytes or cardiovascular progenitors, compared with human bone marrow-derived cells in the repair of tissue damaged by heart attack in rats. The study showed that embryonic stem cell-derived cardiomyocytes and cardiovascular progenitors surpassed the healing power of bone marrow-derived cells.
A second finding of the study was that despite the cardiovascular progenitors' ability to differentiate into both blood vessels and heart muscle, there was no greater improvement in heart function compared to treatment with the more mature cardiomyocytes alone, suggesting that the more mature and stable heart muscle cells are a better option for future therapies and that they may well exceed the efficacy of bone marrow-derived cells in clinical studies.
"There's no reason to go back to more primitive cells [like cardiovascular progenitors] because they don't seem to have a practical advantage over more definitive cell types [cardiomyocytes] in which the risk for tumor formation is lower," says senior study author Charles Murry of the University of Washington, Seattle. "The other important finding is that both of these populations are far superior to bone marrow-derived cells. This work is a go signal that tells us to keep moving on to more promising and more powerful cell types in human trials."
The experiments, led by first authors Sarah Fernandes and James J.H. Chong, involved injecting the cells in the walls of the heart and measuring how well heart muscle tissue contracted in follow up test four weeks later. About 10 animals receiving each of the three treatment variables, and 10 controls receiving a non-therapeutic cell population, were included in the study. Injections were given 4 days after heart attacks had occurred in the rats, as interventions that are given later don't have as much impact.
James Chong, now an interventional cardiologist at the University of Sydney, added "We have recently had success in regenerating hearts of monkeys using a similar approach of transplanting embryonic stem cell-derived cardiomyocytes. The next goals will be to determine if these large animal experiments show similar improvements in cardiac function, and if so, to begin testing these cells in human patients."
This work was supported by the National Institutes of Health.
Stem Cell Reports, Fernandes and Chong et al.: "Comparison of Human Embryonic Stem Cell-Derived Cardiomyocytes, Cardiovascular Progenitors, and Bone Marrow Mononuclear Cells for Cardiac Repair" http://dx.
Stem Cell Reports, published by Cell Press for the International Society for Stem Cell Research (@ISSCR), is a monthly open-access forum communicating basic discoveries in stem cell research, in addition to translational and clinical studies. The journal focuses on shorter, single-point manuscripts that report original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. For more information, please visit http://www.