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HO-1 gene overexpression enhances the beneficial effects of superparamagnetic iron oxide labeled bone marrow stromal cells transplantation in swine hearts underwent ischemia/reperfusion: an MRI study

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Abstract

To determine the effect of intracoronary transfer of superparamagnetic iron oxide (SPIO) labeled heme oxygenase-1 (HO-1) overexpressed bone marrow stromal cells (BMSCs) in a porcine myocardial ischemia/reperfusion model. Cell apoptosis was assayed and supernatant cytokine concentrations were measured in BMSCs that underwent hypoxia/reoxygen in vitro. Female mini-swines that underwent 1 h LAD occlusion followed by 1 h reperfusion were randomly allocated to receive intracoronary saline (control), 1 × 107 SPIO-labeled BMSCs transfected with pcDNA3.1-Lacz plasmid (Lacz-BMSCs), pcDNA3.1-human HO-1 (HO-1-BMSCs), pcDNA3.1-hHO-1 pretreated with a HO inhibitor, tin protoporphyrin (SnPP, n = 10 each). MRI and postmortem histological analysis were made at 1 week or 3 months thereafter. Post hypoxia/reoxygen in vitro, apoptosis was significantly reduced, supernatant VEGF significantly increased while TNF-α and IL-6 significantly reduced in HO-1-BMSCs group compared with Lacz-BMSCs group (all p < 0.05). Myocardial expression of VEGF was significantly higher in HO-1-BMSCs than in Lacz-BMSCs group at 1 week post transplantation (all p < 0.05). Signal voids induced by the SPIO were detected in the peri-infarction region in all BMSC groups at 1 week but not at 3 months post transplantation and the extent of the hypointense signal was the highest in HO-1-BMSCs group, and histological analysis showed that signal voids represented cardiac macrophages that engulfed the SPIO-labeled BMSCs. Pretreatment with SnPP significantly attenuated the beneficial effects of HO-1-BMSCs. Transplantation of HO-1-overexpressed BMSCs significantly enhanced the beneficial effects of BMSCs on improving cardiac function in this model.

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Acknowledgments

This work was supported by National Basic Research Program in China (no. 30670853).

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Authors and Affiliations

  1. Department of Cardiology, Zhongda Hospital, Southeast University, Nanjing, People’s Republic of China

    Yibo Jiang, Lijuan Chen, Yaoliang Tang, Genshan Ma, Chengxing Shen, Chunmei Qi, Qi Zhu, Yuyu Yao & Naifeng Liu

  2. Division of Cardiovascular Diseases, University of Cincinnati, 231 Albert Sabin Way, ML 0542, Cincinnati, OH, 45267-0542, USA

    Yaoliang Tang

  3. Cardiovascular Department, Zhongda Hospital Southeast University, 210009, Nanjing, People’s Republic of China

    Genshan Ma & Chengxing Shen

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  1. Yibo Jiang
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Correspondence to Genshan Ma or Chengxing Shen.

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Jiang, Y., Chen, L., Tang, Y. et al. HO-1 gene overexpression enhances the beneficial effects of superparamagnetic iron oxide labeled bone marrow stromal cells transplantation in swine hearts underwent ischemia/reperfusion: an MRI study. Basic Res Cardiol 105, 431–442 (2010). https://doi.org/10.1007/s00395-009-0079-2

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