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Stem cells used to repair myocardial infarctions in rats

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Researchers from the Institute for Integrated Cell-Material Sciences (iCeMS) of Kyoto University and the Department of Cardiovascular Surgery of Osaka University have developed effective and convenient cardiac tissue-like constructs (CTLCs) for repairing myocardial infarctions.

Cardiovascular diseases such as infarctions are the leading cause of death globally. A seriously injured heart cannot recover by itself, and heart transplants are the only effective treatment. However, the waiting list for transplants is extremely long. Previous researchers have also used cell transplant technologies to repair injured hearts, but these used CMs organized in two dimensions with a random myofibril structure, which is different from natural heart tissue.

Li Liu, M.D., and Yong Chen, Ph.D., of iCeMS, together with Yoshiki Sawa, M.D., Ph.D., of Osaka University and colleagues, selected a PLGA material approved by the FDA and prepared biodegradable, aligned nanofibers for culturing CMs derived from hiPSCs, successfully creating organized and functional CTLCs.

They found that the CMs infiltrated and enveloped the nanofibers, showing elongation and high organization with upregulated expression of cardiac markers. Their CTLCs demonstrated more robust drug response compared with 2D CMs.

The team also used the CTLCs to simulate the repairing of disconnected and arrhythmia CMs. When used to repair injured rat hearts, the CTLCs showed excellent operability leading to favorable heart function recovery.

Future studies are now being planned to use CTLCs to repair injured hearts of larger animals, before advancing to clinical applications.

High-quality cardiac tissue-like constructs (CTLCs) were created by cultivating hiPSC-CMs on aligned nanofibers made of biodegradable polymer. The multilayered and elongated CMs could promptly be organized at high density along aligned nanofibers, resulting in upregulated cardiac biomarkers and enhanced cardiac functions. When used for drug assessment, CTLCs were much more robust than the 2D conventional control. The CTLCs were used to simulate the repairing of disconnected and arrhythmia CMs in vitro. When used to repair injured rat hearts, the CTLCs showed excellent operability leading to favorable heart function recovery. Image courtesy of Kyoto University iCeMS.

 

Learn more:

http://www.kyoto-u.ac.jp/en/research/research_results/2017/171027_1.html
DOI: http://dx.doi.org/10.1016/j.stemcr.2017.09.007