Bone marrow mesenchymal stem cell transplantation improves radiation-induced heart injury through DNA damage repair in rat model

Radiat Environ Biophys. 2017 Mar;56(1):63-77. doi: 10.1007/s00411-016-0675-0. Epub 2016 Dec 26.

Abstract

Radiotherapy is an effective form of therapy for most thoracic malignant tumors. However, myocardial injury resulting from the high doses of radiation is a severe complication. Here we aimed to study the possibility of reducing radiation-induced myocardial injury with mesenchymal stem cell (MSC) transplantation. We used MSCs extracted from bone marrow (BMSCs) to transplant via the tail vein into a radiation-induced heart injury (RIHI) rat model. The rats were divided into six groups: a Sham group, an IRR (irradiation) group, and four IRR + BMSCs transplantation groups obtained at different time points. After irradiation, BMSC transplantation significantly enhanced the cardiac function in rats. By analyzing the expression of PPAR-α, PPAR-γ, TGF-β, IL-6, and IL-8, we found that BMSC transplantation alleviated radiation-induced myocardial fibrosis and decreased the inflammatory reaction. Furthermore, we found that expression of γ-H2AX, XRCC4, DNA ligase4, and TP53BP1, which are associated with DNA repair, was up-regulated, along with increased secretion of growth factors SDF-1, CXCR4, VEGF, and IGF in rat myocardium in the IRR + BMSCs transplantation groups compared with the IRR group. Thus, BMSC transplantation has the potential to improve RIHI via DNA repair and be a new therapeutic approach for patients with myocardial injury.

Keywords: BMSC transplantation; DNA damage; Heart injury; Radiation; Repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / radiation effects
  • Bone Marrow Cells / cytology*
  • DNA Damage*
  • DNA Repair*
  • Disease Models, Animal
  • Fibrosis
  • Heart / physiopathology
  • Heart / radiation effects
  • Heart Injuries / genetics
  • Heart Injuries / pathology
  • Heart Injuries / physiopathology
  • Heart Injuries / therapy*
  • Mesenchymal Stem Cell Transplantation*
  • Paracrine Communication / radiation effects
  • Radiation Injuries / genetics
  • Radiation Injuries / pathology
  • Radiation Injuries / physiopathology
  • Radiation Injuries / therapy*
  • Rats
  • Rats, Sprague-Dawley