Bone marrow mesenchymal stem cells alleviate the daunorubicin-induced subacute myocardial injury in rats through inhibiting infiltration of T lymphocytes and antigen-presenting cells

Biomed Pharmacother. 2020 Jan:121:109157. doi: 10.1016/j.biopha.2019.109157. Epub 2019 Nov 12.

Abstract

Introduction: Bone marrow mesenchymal stem cells (BMSCs) have been extensively investigated from a perspective on cardiac regeneration therapy. The current study aimed to investigate the protective effect conferred by BMSCs in subacute myocardial injury, and to identify an appropriate BMSC reinfusion time.

Methods: BMSCs were isolated from human bone marrow blood. Daunorubicin (DNR)-induced subacute myocardial models were subsequently established. The rats with DNR-induced subacute myocardial injury were injected with dexrazoxane (DZR) and/or BMSCs at varying time points, after which cardiac function was evaluated by assessing left ventricular ejection fraction (LVEF) and fraction shortening (FS). The myocardial structural changes were analyzed, after which the levels of CD3 and human leukocyte antigen DR (HLA-DR) were examined to further validate the mechanism by which BMSCs could influence subacute myocardial injury.

Results: BMSCs combined with DZR treatment enhanced the cardiac function of rats with DNR-induced myocardial injury, as reflected by increased LVEF and FS. DNR-induced myocardial injuries were mitigated via the application of BMSCs combined with treatment of DZR, accompanied by diminished infiltration or vacuolization. Moreover, BMSCs were observed to alleviate infiltration of T lymphocyte and antigen-presenting cells, as evidenced by reduced expression of CD3 and HLA-DR.

Conclusion: Taken together, this study demonstrates that BMSCs could protect against DNR-induced myocardial injury, especially in the first three days of DNR administration. BMSCs combined with DZR exert a better therapeutic effect, but there are individual differences.

Keywords: Antigen-presenting cells; Bone marrow mesenchymal stem cells; Cardiac function; Subacute myocardial injury; T lymphocytes.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Bone Marrow Cells / immunology
  • Daunorubicin / pharmacology*
  • Humans
  • Male
  • Mesenchymal Stem Cell Transplantation / methods
  • Mesenchymal Stem Cells / immunology*
  • Myocardial Infarction / chemically induced*
  • Myocardial Infarction / immunology*
  • Myocardium / immunology*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / immunology
  • Rats
  • Rats, Sprague-Dawley
  • T-Lymphocytes / immunology*

Substances

  • Daunorubicin