Human Cardiac Mesenchymal Stromal Cells with CD105+CD34- Phenotype Enhance the Function of Post-Infarction Heart in Mice

PLoS One. 2016 Jul 14;11(7):e0158745. doi: 10.1371/journal.pone.0158745. eCollection 2016.

Abstract

Aims: The aim of the present study was to isolate mesenchymal stromal cells (MSC) with CD105+CD34- phenotype from human hearts, and to investigate their therapeutic potential in a mouse model of hindlimb ischemia and myocardial infarction (MI). The study aimed also to investigate the feasibility of xenogeneic MSCs implantation.

Methods and results: MSC isolated from human hearts were multipotent cells. Separation of MSC with CD105+CD34- phenotype limited the heterogeneity of the originally isolated cell population. MSC secreted a number of anti-inflammatory and proangiogenic cytokines (mainly IL-6, IL-8, and GRO). Human MSC were transplanted into C57Bl/6NCrl mice. Using the mouse model of hindlimb ischemia it was shown that human MSC treated mice demonstrated a higher capillary density 14 days after injury. It was also presented that MSC administrated into the ischemic muscle facilitated fast wound healing (functional recovery by ischemic limb). MSC transplanted into an infarcted myocardium reduced the post-infarction scar, fibrosis, and increased the number of blood vessels both in the border area, and within the post-infarction scar. The improvement of left ventricular ejection fraction was also observed.

Conclusion: In two murine models (hindlimb ischemia and MI) we did not observe the xenotransplant rejection. Indeed, we have shown that human cardiac mesenchymal stromal cells with CD105+CD34- phenotype exhibit therapeutic potential. It seems that M2 macrophages are essential for healing and repair of the post-infarcted heart.

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism*
  • Disease Models, Animal
  • Endoglin / metabolism*
  • Fibrosis / pathology
  • Humans
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / therapy*
  • Myocardium / pathology

Substances

  • Antigens, CD34
  • Endoglin

Grants and funding

This work was supported by the Innovative Economy Operational Programme POIG.01.03.01-00 169/09. The study has been co-financed by European Regional Development Fund within the framework of Innovative Economy Operational Programme (axis: Investments in Innovative Undertakings). This work was supported by equipment bought for the purposes of the Project: “Silesian BIO-FARMA. Center for Biotechnology, Bioengineering, and Bioinformatics” cofinanced by European Regional Development Fund within the framework of Innovative Economy Operational Programme 2007-2013.