Stretchable Piezoelectric Substrate Providing Pulsatile Mechanoelectric Cues for Cardiomyogenic Differentiation of Mesenchymal Stem Cells

Ex vivo induction of cardiomyogenic differentiation of mesenchymal stem cells (MSCs) before implantation would potentiate therapeutic efficacy of stem cell therapies for ischemic heart diseases because MSCs rarely undergo cardiomyogenic differentiation following implantation. In cardiac microenviron...

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Bibliographic Details
Published in:ACS applied materials & interfaces 2017-07, Vol.9 (27), p.22101-22111
Main Authors: Yoon, Jeong-Kee, Lee, Tae Il, Bhang, Suk Ho, Shin, Jung-Youn, Myoung, Jae-Min, Kim, Byung-Soo
Format: Article
Language:English
Subjects:
Cell Differentiation
Cells, Cultured
Humans
Mesenchymal Stem Cells
Myocytes, Cardiac
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Summary:Ex vivo induction of cardiomyogenic differentiation of mesenchymal stem cells (MSCs) before implantation would potentiate therapeutic efficacy of stem cell therapies for ischemic heart diseases because MSCs rarely undergo cardiomyogenic differentiation following implantation. In cardiac microenvironments, electric pulse and cyclic mechanical strain are sequentially produced. However, no study has applied the pulsatile mechanoelectric cues (PMEC) to stimulate cardiomyogenic differentiation of MSCs ex vivo. In this study, we developed a stretchable piezoelectric substrate (SPS) that can provide PMEC to human MSCs (hMSCs) for cardiomyogenic differentiation ex vivo. Our data showed that hMSCs subjected to PMEC by SPS underwent promoted cardiac phenotype development: cell alignment and the expression of cardiac markers (i.e., cardiac transcription factors, structural proteins, ion channel proteins, and gap junction proteins). The enhanced cardiac phenotype development was mediated by the upregulation of cardiomyogenic differentiation-related autocrine factor expression, focal adhesion kinase, and extracellular signal-regulated kinases signaling pathways. Thus, SPS providing electrical and mechanical regulation of stem cells may be utilized to potentiate hMSC therapies for myocardial infarction and provide a tool for the study of stem cell biology.
ISSN:1944-8244
1944-8252
DOI:10.1021/acsami.7b03050