Cardiac stem cell secretome protects cardiomyocytes from hypoxic injury partly via monocyte chemotactic protein-1-dependent mechanism

Chi Yeon Park, Seung Cheol Choi, Jong Ho Kim, Ji Hyun Choi, Hyung Joon Joo, Soon Jun Hong, Do Sun Lim

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Cardiac stemcells (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- CSCshTERT), evaluated their stem cell properties, and paracrine potential in cardiomyocyte survival during hypoxia-induced injury. Sca-1+/CD31- CSCshTERTsustained 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- CSCshTERT 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-CSCshTERT conditioned medium (CM). Sca-1+/CD31- CSCshTERT CM increased survival and reduced apoptosis of HL-1 cardiomyocytes during hypoxic injury. MCP-1 silencing in Sca-1+/CD31- CSCshTERT CM resulted in a significant reduction in cardiomyocyte apoptosis. We demonstrated that Sca-1+/CD31- CSCshTERT exhibited long-term proliferation capacity and multi-differentiation potential. Sca-1+/CD31- CSCshTERT 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.

Original languageEnglish
Article number800
JournalInternational journal of molecular sciences
Volume17
Issue number6
DOIs
Publication statusPublished - 2016 Jun

Keywords

  • Cardiac stem cells
  • Cardiomyocyte survival
  • Immortalization
  • MCP-1
  • Secretome

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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