Conditioned medium from human amniotic mesenchymal stromal cells limits infarct size and enhances angiogenesis

Stem Cells Transl Med. 2015 May;4(5):448-58. doi: 10.5966/sctm.2014-0253. Epub 2015 Mar 30.

Abstract

The paracrine properties of human amniotic membrane-derived mesenchymal stromal cells (hAMCs) have not been fully elucidated. The goal of the present study was to elucidate whether hAMCs can exert beneficial paracrine effects on infarcted rat hearts, in particular through cardioprotection and angiogenesis. Moreover, we aimed to identify the putative active paracrine mediators. hAMCs were isolated, expanded, and characterized. In vitro, conditioned medium from hAMC (hAMC-CM) exhibited cytoprotective and proangiogenic properties. In vivo, injection of hAMC-CM into infarcted rat hearts limited the infarct size, reduced cardiomyocyte apoptosis and ventricular remodeling, and strongly promoted capillary formation at the infarct border zone. Gene array analysis led to the identification of 32 genes encoding for the secreted factors overexpressed by hAMCs. Among these, midkine and secreted protein acidic and rich in cysteine were also upregulated at the protein level. Furthermore, high amounts of several proangiogenic factors were detected in hAMC-CM by cytokine array. Our results strongly support the concept that the administration of hAMC-CM favors the repair process after acute myocardial infarction.

Keywords: Cardiac; Clinical translation; Fetal stem cells; Placenta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amniotic Fluid / cytology
  • Amniotic Fluid / metabolism
  • Animals
  • Cardiotonic Agents / pharmacology
  • Cell- and Tissue-Based Therapy*
  • Culture Media, Conditioned / pharmacology
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Myocardial Infarction / pathology
  • Myocardial Infarction / therapy*
  • Neovascularization, Physiologic / drug effects*
  • Rats

Substances

  • Cardiotonic Agents
  • Culture Media, Conditioned