Cardiac muscles on-a-chip may provide insight into improved stem cell therapies for heart attacks

A team of researchers from Harvard University (MA, USA) have developed a microtissue model that could help explain why cell transplantation is sometimes ineffective in restoring normal cardiac function in heart attack patients.

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Feb 16, 2016

Researchers at Harvard University (MA, USA) have developed a 'Muscle On-A-Chip' method to find better approaches to repair damaged heart cells following a heart attack. This has led to a clearer understanding of stem cell-derived treatment and may explain why stem cell-based therapies have shown limited benefits for heart failure patients in clinical trials so far.

The possibility of using stem cells to replace damaged heart tissue following a heart attack has been of interest to researchers for numerous years. Although stem cells transplanted into patients can develop into cardiomyocytes (heart muscle cells) and integrate with undamaged regions of cardiac tissue, several preclinical studies and clinical trials have failed to identify significant improvements in the contractile function of the heart. One explanation for this problem could be that mechanical forces are not transmitted properly between the new stem cell-derived cardiomyocytes and the old surviving heart cells.

Mechanical forces exchanged by cardiomyocytes are impossible to measure in patients. To overcome this, a team of researchers led by Kit Parker from Harvard University developed a simplified in vitro system in which single heart cells isolated from mice are combined with individual, stem cell-derived cardiomyocytes to form a two-cell microtissue called 'muscle on-a-chip'.

Using this approach, the research team found that stem cell-derived cardiomyocytes could structurally couple, and synchronously beat with mouse cardiomyocytes. Stem cell-derived myocytes contracted less strongly than their partners and this imbalance resulted in the cells transmitting mechanical forces to their surroundings, instead of to each other.

Furthermore, computer simulations revealed that the unequal forces generated by stem cell-derived and native cardiomyocytes are sufficient to induce the formation of cellular adhesions that can dissipate force to the cells' surroundings. The model also suggested that human cardiomyocytes are likely to behave similarly.

Inefficient force transmission could explain why stem cell transplantation has been somewhat ineffective in restoring normal heart function. Parker and colleagues' muscle on-a-chip technique may help researchers develop ways to improve the mechanical coupling of stem cell-derived cardiomyocytes to surviving heart tissue with the aim to improve patient outcomes.

Sources:;; 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. doi:10.1083/jcb.201508026 (2016) (Epub ahead of print)

Go to the profile of Elena Conroy

Elena Conroy

Contributor, Future Science Group

If you have any interest in submitting to the journal Regenerative Medicine or have any queries, please don't hesitate to contact my colleague Adam, Commissioning Editor of the journal

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