title: Cardiac Stem Cell Secretome Protects Cardiomyocytes from Hypoxic Injury Partly via Monocyte Chemotactic Protein-1-Dependent Mechanism.
abstract: Cardiac stem cells (CSCs) were known to secrete diverse paracrine factors leading to functional improvement and beneficial left ventricular remodeling via activation of the endogenous pro-survival signaling pathway. However, little is known about the paracrine factors secreted by CSCs and their roles in cardiomyocyte survival during hypoxic condition mimicking the post-myocardial infarction environment. We established Sca-1+/CD31- human telomerase reverse transcriptase-immortalized CSCs (Sca-1+/CD31- CSCs(hTERT)), evaluated their stem cell properties, and paracrine potential in cardiomyocyte survival during hypoxia-induced injury. Sca-1+/CD31- CSCs(hTERT) sustained proliferation ability even after long-term culture exceeding 100 population doublings, and represented multi-differentiation potential into cardiomyogenic, endothelial, adipogenic, and osteogenic lineages. Dominant factors secreted from Sca-1+/CD31- CSCs(hTERT) were EGF, TGF-β1, IGF-1, IGF-2, MCP-1, HGF R, and IL-6. Among these, MCP-1 was the most predominant factor in Sca-1+/CD31- CSCs(hTERT) conditioned medium (CM). Sca-1+/CD31- CSCs(hTERT) CM increased survival and reduced apoptosis of HL-1 cardiomyocytes during hypoxic injury. MCP-1 silencing in Sca-1+/CD31- CSCs(hTERT) CM resulted in a significant reduction in cardiomyocyte apoptosis. We demonstrated that Sca-1+/CD31- CSCs(hTERT) exhibited long-term proliferation capacity and multi-differentiation potential. Sca-1+/CD31- CSCs(hTERT) CM protected cardiomyocytes from hypoxic injury partly via MCP-1-dependent mechanism. Thus, they are valuable sources for in vitro and in vivo studies in the cardiovascular field.
authors.affiliation: Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul 02841, Korea. chiyoun@korea.ac.kr.
authors.forename: Chi-Yeon
authors.initials: CY
authors.lastname: Park
authors.affiliation: Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul 02841, Korea. choisc86@gmail.com.
authors.forename: Seung-Cheol
authors.initials: SC
authors.lastname: Choi
authors.affiliation: Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul 02841, Korea. mecey@naver.com.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul 02841, Korea. j2610@hanmail.net.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul 02841, Korea. drjoohj@gmail.com.
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Joo
authors.affiliation: Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul 02841, Korea. psyche94@gmail.com.
authors.forename: Soon Jun
authors.initials: SJ
authors.lastname: Hong
authors.affiliation: Department of Cardiology, Cardiovascular Center, College of Medicine, Korea University, Seoul 02841, Korea. dslmd@kumc.or.kr.|Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, 73, Inchon-ro, Seongbuk-gu, Seoul 02841, Korea. dslmd@kumc.or.kr.
authors.forename: Do-Sun
authors.initials: DS
authors.lastname: Lim
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000166:cytology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C509186:TERT protein, human; D019098:Telomerase
keywords: MCP-1; cardiac stem cells; cardiomyocyte survival; immortalization; secretome