Cardiac Stem Cell Secretome Protects Cardiomyocytes from Hypoxic Injury Partly via Monocyte Chemotactic Protein-1-Dependent Mechanism

Int J Mol Sci. 2016 May 24;17(6):800. doi: 10.3390/ijms17060800.


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.

Keywords: MCP-1; cardiac stem cells; cardiomyocyte survival; immortalization; secretome.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Hypoxia
  • Cell Proliferation
  • Cell Survival
  • Cells, Cultured
  • Chemokine CCL2 / metabolism*
  • Humans
  • Mice
  • Models, Biological
  • Myocytes, Cardiac / cytology*
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Telomerase / genetics*


  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Platelet Endothelial Cell Adhesion Molecule-1
  • TERT protein, human
  • Telomerase