Copyright
©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
Regenerative potential of mouse embryonic stem cell-derived PDGFRα+ cardiac lineage committed cells in infarcted myocardium
Seon Pyo Hong, Sukhyun Song, Seungjoo Lee, Hyeonju Jo, Hyoung Kyu Kim, Jin Han, Jae-Hyeong Park, Sung Woo Cho
Seon Pyo Hong, Sukhyun Song, Center for Vascular Research, Institute of Basic Science (IBS), Daejeon 34141, South Korea
Seungjoo Lee, Department of Neurosurgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, South Korea
Hyeonju Jo, Hyoung Kyu Kim, Jin Han, Cardiovascular and Metabolic Disease Center, Department of Physiology, Department of Health Sciences and Technology, BK21 plus Project Team, Inje University College of Medicine, Busan 47392, South Korea
Jae-Hyeong Park, Department of Cardiology in Internal Medicine, School of Medicine, Chungnam National University Hospital, Chungnam National University, Daejeon 35015, South Korea
Sung Woo Cho, Division of Cardiology, Department of Internal Medicine, Inje University College of Medicine, Seoul Paik Hospital, Seoul 04551, South Korea
Sung Woo Cho, Cardiovascular and Metabolic Disease Center, Inje University College of Medicine, Busan 47392, South Korea
Author contributions: Hong SP and Song S contributed equally to this work; Hong SP and Song S performed the majority of experiments; Hong SP, Song S and Cho SW conceptualized the original idea, designed the experiments and analyzed the data; Hong SP and Lee S made myocardial infarction murine models; Park JH performed the transthoracic echocardiography and analyzed the data; Jo H, Kim HK and Han J coordinated and supervised the research; Hong SP, Song S and Cho SW wrote the paper.
Supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, No. 2017R1D1A3B03034465; the 2017 Inje University research grant, and Priority Research Centers Program through the NRF funded by the Ministry of Education, Science, and Technology, No. 2010-0020224.
Institutional animal care and use committee statement: Approved by the Animal Care Committee of KAIST (KA2013-40).
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Sung Woo Cho, MD, PhD, Assistant Professor, Division of Cardiology, Department of Internal Medicine, Inje University College of Medicine, Seoul Paik Hospital, 9 Mareunnae-ro, Jung-gu, Seoul 04551, South Korea.
drswcho@hanmail.net
Telephone: +82-2-22700010 Fax: +82-2-22700312
Received: October 29, 2018
Peer-review started: October 29, 2018
First decision: November 29, 2018
Revised: December 6, 2018
Accepted: January 5, 2019
Article in press: January 6, 2019
Published online: January 26, 2019
Processing time: 90 Days and 18.8 Hours
ARTICLE HIGHLIGHTS
Research background
Pluripotent stem cell (PSC)-derived cardiomyocytes (CMs) have become one of the most attractive cellular resources for cell-based therapy to rescue damaged cardiac tissue.
Research motivation
The proliferative capacity of PSC-derived CMs is decreased after beating and terminal differentiation. Furthermore, there is no definite surface marker of differentiated PSC-derived CMs to facilitate purification.
Research objectives
We investigated the regenerative potential of mouse embryonic stem cell-derived PDGFRα+ cardiac lineage-committed cells (CLCs) in a murine myocardial infarction (MI) model and compared their efficacy with differentiated CMs.
Research methods
We implanted platelet-derived growth factor receptor-α (PDGFRα)+ CLCs and differentiated αMHC+ CMs into a MI murine model and performed functional analysis using transthoracic echocardiography (TTE) and histologic analysis.
Research results
Compared with the untreated MI hearts, the anterior and septal regional wall motion and systolic functional parameters were notably and similarly improved in the MI hearts implanted with PDGFRα+ CLCs and αMHC+ CMs based on TTE. In histologic analysis, the untreated MI hearts contained a thinner ventricular wall than did the controls, while the ventricular walls of MI hearts implanted with PDGFRα+ CLCs and αMHC+ CMs were similarly thicker compared with that of the untreated MI hearts. Furthermore, implanted PDGFRα+ CLCs aligned and integrated with host CMs and were mostly differentiated into α-actinin+ CMs, and they did not convert into CD31+ endothelial cells or αSMA+ mural cells.
Research conclusions
PDGFRα+ CLCs from mouse ESCs exhibiting proliferative capacity showed a regenerative effect in infarcted myocardium. Therefore, mouse ESC-derived PDGFRα+ CLCs may represent a potential cellular resource for cardiac regeneration.
Research perspectives
PDGFRα+ CLCs served as the potential donor population for cardiac regeneration, and our findings provide conceptual and technical advances in stem cell therapy for cardiac regeneration.
