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Pericardial application as a new route for implanting stem-cell cardiospheres to treat myocardial infarction

Zhang, J, Wu, Z, Fan, Z, Qin, Z, Wang, Y, Chen, J, Wu, M, Chen, Y, Wu, Changhao and Wang, J (2018) Pericardial application as a new route for implanting stem-cell cardiospheres to treat myocardial infarction Journal of Physiology, 596 (11). pp. 2037-2054.

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Cardiospheres (CSps) are a new form of cardiac stem cells with the advantage over other stem cells for myocardial regeneration. However, direct implantation of CSps by conventional routes to treat myocardial infarction has been limited due to potential embolism. We have implanted CSps into pericardial cavity and systematically assessed its efficacy on myocardial infarction. Preconditioning with pericardial fluid enhanced the activity of CSps and matrix hydrogel prolonged their viability. This shows pretransplant optimization of stem cell potency and maintenance of cell viability can be achieved with CSps. Transplantation of optimized CSps into pericardial cavity improved cardiac function and alleviated myocardial fibrosis in non-infarcted area, and increased myocardial cell survival and promoted angiogenesis in the infarcted area. Mechanistically, CSps were able to directly differentiate into cardiomyocytes in vivo and promoted regeneration of myocardial cells and blood vessels in the infarcted area through a paracrine effect with released growth factors in pericardial cavity serving as possible paracrine mediators. This is the first demonstration of direct pericardial administration of pre-optimized CSps, and its effectiveness on myocardial infarction by functional and morphological outcomes with distinct mechanisms. These findings establish a new strategy for therapeutic myocardial regeneration to treat myocardial infarction.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
Zhang, J
Wu, Z
Fan, Z
Qin, Z
Wang, Y
Chen, J
Wu, M
Chen, Y
Wang, J
Date : 1 June 2018
Funders : BBSRC
DOI : 10.1113/JP275548
Copyright Disclaimer : Copyright 2018 The Authors. The Journal of Physiology is published by John Wiley & Sons Ltd on behalf of The Physiological Society. DOI: 10.1113/JP275548. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords : cardiospheres (CSps); pericardial fluid from rats with myocardial infarction (PFMI); Matrix hydrogel;pericardial cavity; myocardial infarction
Depositing User : Melanie Hughes
Date Deposited : 15 Feb 2018 09:38
Last Modified : 11 Jun 2019 15:25

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