Oncotarget

Research Papers: Cardiology:

Platelet-derived growth factor receptor-alpha positive cardiac progenitor cells derived from multipotent germline stem cells are capable of cardiomyogenesis in vitro and in vivo

Bang-Jin Kim, Yong-Hee Kim, Yong-An Lee, Sang-Eun Jung, Yeong Ho Hong, Eun-Ju Lee, Byung-Gak Kim, Seongsoo Hwang, Jeong Tae Do, Myung-Geol Pang and Buom-Yong Ryu _

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Oncotarget. 2017; 8:29643-29656. https://doi.org/10.18632/oncotarget.16772

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Abstract

Bang-Jin Kim1,7, Yong-Hee Kim1, Yong-An Lee2, Sang-Eun Jung1, Yeong Ho Hong1, Eun-Ju Lee3, Byung-Gak Kim4, Seongsoo Hwang5, Jeong Tae Do6, Myung-Geol Pang1 and Buom-Yong Ryu1

1 Department of Animal Science & Technology, Chung-Ang University, Anseong, Republic of Korea

2 Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore

3 Department of Internal medicine, Seoul National University, Seoul, Republic of Korea

4 Bio Environment Technology Research Institute, Chung-Ang University, Anseong, Republic of Korea

5 Animal Biotechnology Division, National Institute of Animal Science, Jeollabuk-do, Republic of Korea

6 Department of Stem Cell and Regenerative Biology, College of Animal Bioscience and Technology, Konkuk University, Seoul, Republic of Korea

7 Department of Cancer Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America

Correspondence to:

Buom-Yong Ryu, email:

Keywords: germ-line stem cells; multipotent; testis; cardiac progenitor; differentiation

Received: September 24, 2016 Accepted: February 28, 2017 Published: March 31, 2017

Abstract

Cardiac cell therapy has the potential to revolutionize treatment of heart diseases, but its success hinders on the development of a stem cell therapy capable of efficiently producing functionally differentiated cardiomyocytes. A key to unlocking the therapeutic application of stem cells lies in understanding the molecular mechanisms that govern the differentiation process. Here we report that a population of platelet-derived growth factor receptor alpha (PDGFRA) cells derived from mouse multipotent germline stem cells (mGSCs) were capable of undergoing cardiomyogenesis in vitro. Cells derived in vitro from PDGFRA positive mGSCs express significantly higher levels of cardiac marker proteins compared to PDGFRA negative mGSCs. Using Pdgfra shRNAs to investigate the dependence of Pdgfra on cardiomyocyte differentiation, we observed that Pdgfra silencing inhibited cardiac differentiation. In a rat myocardial infarction (MI) model, transplantation of a PDGFRAenriched cell population into the rat heart readily underwent functional differentiation into cardiomyocytes and reduced areas of fibrosis associated with MI injury. Together, these results suggest that mGSCs may provide a unique source of cardiac stem/progenitor cells for future regenerative therapy of damaged heart tissue.


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