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

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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.

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Acknowledgements

We would like to express our thanks for the guidance of Enyang Wang and Fuda Xiao.

Funding

This study was supported by the National Natural Foundation of China (Grant Numbers: 81370717 and 81171072) as well as the National 973 project of China (Grant Number: 2013CB945402).

Author contributions

SG designed and performed all the experiments and wrote the manuscript; RW guided the development of the experimental animal model; YCZ, ZYZ and JNM helped do the experiments. ZYZ analyzed the data and helped with drawing the figures; ZWY supervised the project and wrote the manuscript with SG.

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Authors and Affiliations

  1. The Second Department of Clinical Oncology, Shengjing Hospital, China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang, 110022, China

    Song Gao, Rong Wu, Yuecan Zeng & Zhenyong Zhang

  2. School of Computer Science and Engineering, Northeastern University, No. 3-11, Wenhua Road, Heping District, Shenyang, 110004, China

    Zhiying Zhao

  3. Key Laboratory of Shengjing Hospital, China Medical University, No. 7, Economic Development Zone, Benxi, Shenyang, 117004, China

    Jianing Miao

  4. Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, No. 7, Economic Development Zone, Benxi, 117004, China

    Zhengwei Yuan

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  1. Song Gao
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  2. Zhiying Zhao
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Correspondence to Zhengwei Yuan.

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Human and animal rights statement

All animal treatment protocols in this study adhered to the National Institutes of Health Guide for Care and Use of Laboratory Animals, and were approved by the Institutional Animal Care and Use Board of Shengjing Hospital of China Medical University.

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Gao, S., Zhao, Z., Wu, R. et al. Bone marrow mesenchymal stem cell transplantation improves radiation-induced heart injury through DNA damage repair in rat model. Radiat Environ Biophys 56, 63–77 (2017). https://doi.org/10.1007/s00411-016-0675-0

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