Previous attempts at restoring damaged heart tissue through the use of stem cell derived heart muscle cells have shown limited success. New research, published in The Journal of Cell Biology, may provide the answers needed to explain the poor outcomes thus far in clinical trials.
The prospect of using stem cell derived cardiomyocytes to replace damaged heart tissue has been of significant interest to researchers for a number of years. Although differentiation and successful integration of cardiomyocytes into heart tissue has been previously observed, pre-clinical and clinical studies fail to identify any noticeable improvement in the contractile function of a damaged heart.
This could be explained by the improper transmission of mechanical forces between the stem cell-derived cardiomyocytes and the surviving heart cells. Given that the mechanical forces exchanged by cardiomyocytes are almost impossible to measure in patients, Harvard University researchers developed an in vitro system where isolated mouse heart cells are combined with individual, stem cell-derived cardiomyocytes to form a two-cell “microtissue”. The researchers named this as a “muscle on-a-chip.”
Researchers found that the stem cell derived cardiomyocytes could couple with and synchronously beat with mouse cardiomyocytes. The stem cell derived cardiomyocytes were found to contract less strongly than their partners causing an imbalance that resulted in the transmission of mechanical forces to the surroundings instead of to each other. Using computer simulations, the unequal forces were found to be sufficient enough to induce the formation of cellular adhesions which can dissipate the forces to the surroundings.
Through these finding, the inefficient force transmission may be the reason as to why stem cell transplantation has not been effective at restoring heart function. The team’s muscle on-a-chip could become a valuable tool in improving the coupling of stem cell-derived cardiomyocytes to surviving heart tissue.
Source: Muscles on-a-Chip Provide Insight Into Cardiac Stem Cell Therapies; Press Release
Aratyn-Schaus Y, Pasqualini FS, Yuan H, et al. Coupling primary and stem cell–derived cardiomyocytes in an in vitro model of cardiac cell therapy. J Cell Biol, February 8, 2016 DOI