title: Bone marrow mesenchymal stem cell transplantation improves radiation-induced heart injury through DNA damage repair in rat model.
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.
authors.affiliation: The Second Department of Clinical Oncology, Shengjing Hospital, China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang, 110022, China.
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.affiliation: School of Computer Science and Engineering, Northeastern University, No. 3-11, Wenhua Road, Heping District, Shenyang, 110004, China.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: The Second Department of Clinical Oncology, Shengjing Hospital, China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang, 110022, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.affiliation: The Second Department of Clinical Oncology, Shengjing Hospital, China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang, 110022, China.
authors.forename: Yuecan
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: The Second Department of Clinical Oncology, Shengjing Hospital, China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang, 110022, China.
authors.forename: Zhenyong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Shengjing Hospital, China Medical University, No. 7, Economic Development Zone, Benxi, Shenyang, 117004, China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Miao
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, No. 7, Economic Development Zone, Benxi, 117004, China. yuanzw@hotmail.com.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000818:Animals; D001835:Body Weight / Q000528:radiation effects; D001854:Bone Marrow Cells / Q000166:cytology*; D004249:DNA Damage; D004260:DNA Repair; D004195:Disease Models, Animal; D005355:Fibrosis; D006321:Heart / Q000503:physiopathology / Q000528:radiation effects; D006335:Heart Injuries / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D019899:Paracrine Communication / Q000528:radiation effects; D011832:Radiation Injuries / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: BMSC transplantation; DNA damage; Heart injury; Radiation; Repair