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Intramyocardial injection of hypoxia-preconditioned adipose-derived stromal cells treats acute myocardial infarction: an in vivo study in swine

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Abstract

Hypoxic preconditioning is a promising method for improving the anti-apoptotic and paracrine signaling capabilities of adipose-derived stromal cells (ADSCs). The purpose of this study was to analyze the influence of different hypoxic conditions on ADSCs and the therapeutic effects of hypoxia-preconditioned ADSCs (HPADSCs) on an animal model of myocardial infarction (MI). For the in vitro studies, ADSCs were divided into five groups and cultured in different oxygen concentrations (1, 3, 5, 10, and 21 %). After 24 h, RT-PCR and western blots showed that 3 % oxygen preconditioning could improve the viability and cytokine secretion of the ADSCs. A Matrigel assay indicated that the HPADSC-conditioned medium could stimulate endothelial cells to form capillary-like tubes. For the in vivo studies, MI was induced by coronary occlusion in 24 mature Chinese minipigs. The animals were divided into three groups and treated by intramyocardial injection with vehicle alone (saline group), with 1 × 108 ADSCs cultured in normoxic conditions (ADSCs group) or with 1 × 108 ADSCs precultured in 3 % oxygen (HPADSCs group). SPECT and echocardiography demonstrated that cardiac function was improved significantly in the HPADSC transplant group compared with the vehicle control group (P < 0.05). Immunofluorescence showed fewer apoptotic cells and more small- to medium-sized vessels in the HPADSC transplantation group (P < 0.05). Three percent oxygen is the optimum preconditioning treatment for ADSCs. HPADSC transplantation can prevent ventricular remodeling and reduce the infarct size.

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Acknowledgments

This work was supported by Tianjin Binhai New Area Health Bureau projects (Grants: 2012BWKZ009), the State High-tech Research and Development Plan (Grants: 2011AA020109) and China National Natural Science Foundation (Grants: 81301217). Alliancells Bioscience Co. Ltd. is also gratefully acknowledged for assistance with ADSC.

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Authors and Affiliations

  1. Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital Cardiovascular Clinical Hospital of Tianjin Medical University, 61# Third Avenue Tianjin Economic Development Area, Tianjin, 300457, China

    Yiyao Jiang, Yu Pei, Yongjun Liu, Delin Zhu & Xiaocheng Liu

  2. Department of Radiation Oncology in the First Bethune Hospital of Jilin University Changchun, Jilin, 130021, China

    Pengyu Chang

  3. Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China

    Yu Pei & Xiaocheng Liu

  4. Department of Pathology, the Fifth Central Hospital of Tianjin, Tianjin, 300450, China

    Baojiang Li

  5. Alliancells Biosciences Co., Ltd, 45 Dongjiu Road, Airport Economic Area, Tianjin, 300304, China

    Yongjun Liu & Delin Zhu

  6. Department of Radiology, Tianjin Medical University General Hospital, Tianjin, 300052, China

    Zhang Zhang

  7. Department of Radiology, Tianjin First Center Hospital, Tianjin, 300192, China

    Jing Yu

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  1. Yiyao Jiang
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  2. Pengyu Chang
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  3. Yu Pei
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  8. Delin Zhu
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  9. Xiaocheng Liu
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Correspondence to Delin Zhu or Xiaocheng Liu.

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Jiang, Y., Chang, P., Pei, Y. et al. Intramyocardial injection of hypoxia-preconditioned adipose-derived stromal cells treats acute myocardial infarction: an in vivo study in swine. Cell Tissue Res 358, 417–432 (2014). https://doi.org/10.1007/s00441-014-1975-9

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  • DOI: https://doi.org/10.1007/s00441-014-1975-9

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