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Modulation of Stem Cell Fate by Electrical Stimulation

Kim, Sun Wook
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1383812480

Abstract Details

2013, PhD, University of Cincinnati, Medicine: Systems Biology and Physiology.
Survival of stem cells following transplantation in the infarcted myocardium is a critical issue for the cell-based therapy and preconditioning of stem cells is one of the most powerful stimulus for cytoprotection. The heart and cardiac cells are intrinsically exposed to EleS during its life span, suggesting that EleS might have a function in cardiac cells beyond stimulation of contraction. Also, EleS has been explored for induction of cardiac or muscle differentiation by various stem cells. In this study, we investigated the potential of EleS as a preconditioning tool for enhancing of cardiac stem cells (CSCs) survival after transplantation in the infarcted heart and determined its underlying molecular mechanisms. Sca-1+ CSCs were isolated from male C57BL6 mice (12 weeks) hearts. preconditioning of CSCs with EleS (EleSCSCs) was carried out for 3 h at 1.5 V followed by exposure to 300 µM H2O2 for 5 h. Cytoprotective effects and cell adhesion were significantly increased by EleS as evaluated by TUNEL, lactate dehyrogenase release, and cell adhesion assay. EleS increased phosphorylation of AKT, focal adhesion kinase (FAK) and glycogen synthase kinase (GSK3ß), and decreased pro-apoptotic protein caspase-3 cleavage. Pretreatment with Wortmannin, a PI3K inhibitor, and FAK inhibitor-14 abolished the pro-survival effects of EleS. Importantly, we found that connective tissue growth factor (Ctgf) was responsible for EleS-induced CSC survival and adhesion. Interestingly, EleS increased CSC survival in vivo as well as restoration of cardiac function. The knockdown of Ctgf abolished EleS-induced cytoprotective effects and cardiac function recovery. EleS enhanced CSCs survival and differentiation through expression of miRNAs (miRs). The activities of miRs depended on duration and potential of EleS. In relation to EleS-induced CSCs survival, miR-378 played asignificant role in EleS through Ctgf regulation in CSCs. EleS upregulated the cardiac genes such as Nkx2.5, cTnT, cTnI as well as specific miRs which were predicted to target cardiac marker genes. It is concluded that EleS is a promising preconditioning method for enhancing cell survival and cardiac diffentiation of CSCs. It enhanced CSC survival in vitro and in vivo through the AKT/FAK/CTGF cascade involved in cell adhesion signaling. miR-378 was important target for CTGF in the preconditioned CSCs prior to their transplantation in the heart. Our results suggest that EleS is a promising approach for preconditioning of stem cells.
Evangelia Kranias, Ph.D. (Committee Chair)
Muhammad Ashraf, Ph.D. (Committee Member)
Mohammed Matlib, Ph.D. (Committee Member)
Richard Paul, Ph.D. (Committee Member)
Roger Worrell, Ph.D. (Committee Member)
Yana Zavros, Ph.D. (Committee Member)
177 p.
Physiological Psychology
Electrical stimulation; Stem cell therapy; Connective tissue growth factor; miRNAs; Myocardial infarction; Cardiac differentiation

Recommended Citations

Citations

  • Kim, S. W. (2013). Modulation of Stem Cell Fate by Electrical Stimulation [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1383812480

    APA Style (7th edition)

  • Kim, Sun Wook. Modulation of Stem Cell Fate by Electrical Stimulation. 2013. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1383812480.

    MLA Style (8th edition)

  • Kim, Sun Wook. "Modulation of Stem Cell Fate by Electrical Stimulation." Doctoral dissertation, University of Cincinnati, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1383812480

    Chicago Manual of Style (17th edition)

ucin1383812480
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© 2013, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.