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Vascular Endothelial Growth Factor Enhanced the Angiogenesis Response of Human Umbilical Cord-Derived Mesenchymal Stromal Cells in a Rat Model of Radiation Myelopathy

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Abstract

The present study was designed to examine a synergistic role for VEGF and human umbilical cord-derived MSCs (UC-MSCs) therapy in a rat model of radiation myelopathy. UC-MSCs and VEGF were injected through the tail vein at 90, 97, 104 and 111 days post-irradiation. Behavioral tests were performed, and histological damage was examined. The microcirculation in the spinal cord was assessed using von Willebrand factor immunohistochemical analysis and laser-Doppler flowmetry. The microenvironment in the spinal cord was determined by measuring the pro-inflammatory cytokines interleukin-1β and tumor necrosis factor-α in the serum and the anti-inflammatory cytokines brain-derived neurotrophic factor and glial cell-derived neurotrophic factor in the spinal cord. The UC-MSCs processed with VEGF, including VEGF165-induced UC-MSC (iUC), VEGF and UC-MSCs (VEGF-UC), increased the endothelial cell density and the microvessel density in the white matter and gray matter of the spinal cord, raised the relative magnitude of spinal cord blood flow compared to UC-MSCs treatment alone. Our data provided the first evidence that vascular endothelial growth factor enhanced the angiogenesis response of human umbilical cord-derived mesenchymal stromal cells in a rat model of radiation myelopathy.

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Acknowledgments

This work was primarily supported by a Grant from the Fundamental Research Funds for nonprofit public scientific research institutions of Chongqing from Chongqing Science and Technology Commission (Grant no. 2015CSTC-JBKY-01702 to L. Wei). It was partially supported by Grants from the National Natural Science Foundation of China (NSFC Grant Numbers 81001220 and 81370077 to H. You), the Affiliated Hospital of the Academy of Military Medical Sciences (to H. You), and the 12th Five-Year Project of PLA China (to H. You). H. You is supported in part by a RONPAKU Fellowship (ID No: R11301) from the Japan Society for the Promotion of Science (JSPS). We thank Prof. Shigetaka Yoshida at Asahikawa Medical University in Japan for supervising the revision process of the manuscript.

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Authors and Affiliations

  1. Affiliated Hospital of the Academy of Military Medical Sciences, Beijing, 100071, China

    Hua You & Jing Zhang

  2. Key Laboratory of Birth Defects and Reproductive Health of the National Health and Family Planning Commission, Chongqing Population and the Family Planning Science and Technology Research Institute, Chongqing, 400020, China

    Li Wei

  3. Department of Cardiology, Institute of Clinical Medicine, Hubei University of Medicine, Shiyan, 442000, Hubei, China

    Jia-Ning Wang

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  1. Hua You
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Correspondence to Li Wei.

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You, H., Wei, L., Zhang, J. et al. Vascular Endothelial Growth Factor Enhanced the Angiogenesis Response of Human Umbilical Cord-Derived Mesenchymal Stromal Cells in a Rat Model of Radiation Myelopathy. Neurochem Res 40, 1892–1903 (2015). https://doi.org/10.1007/s11064-015-1684-0

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