Muscles on-a-chip provide insight into cardiac stem cell therapies

February 8, 2016, Rockefeller University Press

Stem cell-derived heart muscle cells may fail to effectively replace damaged cardiac tissue because they don't contract strongly enough, according to a study in The Journal of Cell Biology. The study, "Coupling Primary and Stem Cell-Derived Cardiomyocytes in an In Vitro Model of Cardiac Cell Therapy," by Yvonne Aratyn-Schaus and Francesco Pasqualini and colleagues, may help explain why stem cell-based therapies have so far shown limited benefits for heart attack patients in clinical trials.

The possibility of using stem cells to replace damaged tissue following a heart attack has interested researchers for many years. Though transplanted into patients can develop into (cardiomyocytes) and integrate with undamaged regions of , several pre-clinical studies and clinical trials have failed to identify significant improvements in the contractile function of the heart.

One explanation for this could be that mechanical forces are not transmitted properly between the new, stem cell-derived cardiomyocytes and the old, surviving heart cells. The mechanical forces exchanged by cardiomyocytes are impossible to measure in patients. So, a team of researchers led by Professor Kit Parker at 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" that the researchers call a "muscle on-a-chip."

Using this approach, Pasqualini and Aratyn-Schaus, post-doctoral fellows in the Parker lab and co-first authors of the study, 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, however, and this imbalance resulted in the cells transmitting to their surroundings, instead of to each other.

A two-cell "microtissue" contains a mouse embryonic stem cell-derived cardiomyocyte and a mouse neonatal cardiomyocyte. The lower panel shows the traction forces generated as the two cells contract; the stronger, neonatal cardiomyocyte produces more force than the weaker, stem cell-derived cardiomyocyte. Credit: Aratyn-Schause, Y. et al. J Cell Biol. 2016

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 computer model also suggests that human cardiomyocytes are likely to behave similarly.

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

Explore further: Cardiac muscle cells as good as progenitors for heart repair

More information: Aratyn-Schaus, Y., et al. 2016. J Cell Biol. dx.doi.org/10.1083/jcb.201508026

Related Stories

Cardiac muscle cells as good as progenitors for heart repair

October 22, 2015
Stem cell therapies for post-heart attack tissue repair have had modest success at best. Clinical trials have primarily used bone marrow cells, which can promote the growth of new blood vessels, but many studies have shown ...

Electrical stimulation can regulate and synchronize beating properties of nascent heart cells

January 19, 2016
Columbia Engineering researchers have shown, for the first time, that electrical stimulation of human heart muscle cells (cardiomyocytes) engineered from human stem cells aids their development and function. The team used ...

A tool for isolating progenitor cells from human heart tissue could lead to heart repair

October 7, 2015
A*STAR researchers and colleagues have developed a method to isolate and expand human heart stem cells, also known as cardiac progenitor cells, which could have great potential for repairing injured heart tissue.

New research reveals combined cell therapy enhances cardiac performance following heart attack

November 11, 2015
A new study from the Interdisciplinary Stem Cell Institute (ISCI) at the University of Miami Miller School of Medicine finds that combination stem cell therapy, using c-kit+ cardiac stem cells (CSCs) and mesenchymal stem ...

Broken UV light leads to key heart muscle cell discovery

January 19, 2016
For a team of Vanderbilt investigators trying to generate heart muscle cells from stem cells, a piece of broken equipment turned out to be a good thing.

Recommended for you

Exercise may be as effective as prescribed drugs to lower high blood pressure

December 18, 2018
Exercise may be as effective as prescribed drugs to lower high (140 mm Hg) blood pressure, suggests a pooled analysis of the available data, in what is thought to be the first study of its kind, and published online in the ...

Can stem cells help a diseased heart heal itself? Researchers achieve important milestone

December 14, 2018
A team of Rutgers scientists, including Leonard Lee and Shaohua Li, have taken an important step toward the goal of making diseased hearts heal themselves—a new model that would reduce the need for bypass surgery, heart ...

Your weight history may predict your heart failure risk

December 12, 2018
In a medical records analysis of information gathered on more than 6,000 people, Johns Hopkins Medicine researchers conclude that simply asking older adult patients about their weight history at ages 20 and 40 could provide ...

Higher risk of heart attack on Christmas Eve

December 12, 2018
The risk of heart attack peaks at around 10pm on Christmas Eve, particularly for older and sicker people, most likely due to heightened emotional stress, finds a Swedish study in this week's Christmas issue of The BMJ.

Age is the biggest risk for heart disease, but lifestyle and meds have impact

December 12, 2018
Of all the risk factors for heart disease, age is the strongest predictor of potential trouble.

New understanding of mysterious 'hereditary swelling'

December 12, 2018
For the first time ever, biomedical researchers from Aarhus University, Denmark, report cellular defects that lead to a rare disease, hereditary angioedema (HAE), in which patients experience recurrent episodes of swelling ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.