Neural Regeneration Research ›› 2016, Vol. 11 ›› Issue (2): 298-304.doi: 10.4103/1673-5374.177739

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Human neural stem cells promote proliferation of endogenous neural stem cells and enhance angiogenesis in ischemic rat brain

Sun Ryu 1, 4, Seung-Hoon Lee 1, 4, Seung U. Kim 2, 3, Byung-Woo Yoon 1, 4   

  1. 1 Department of Neurology and Clinical Research Institute, Seoul National University Hospital, Seoul National University, Seoul, Republic of Korea
    2 Medical Research Institute, Chung-Ang University School of Medicine, Seoul, Republic of Korea
    3 Department of Neurology, UBC Hospital, University of British Columbia, Vancouver, Canada
    4 Medical Research Center, Seoul National University, Seoul, Republic of Korea
  • Received:2015-12-22 Online:2016-02-15 Published:2016-02-15
  • Contact: Byung-Woo Yoon, M.D., Ph.D., bwyoon@snu.ac.kr.
  • Supported by:

    This work was supported by the Korea Health Technology R&D Project, Ministry of Health & Welfare (HI12C0381), Republic of Korea.

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Abstract:

Transplantation of human neural stem cells into the dentate gyrus or ventricle of rodents has been reportedly to enhance neurogenesis. In this study, we examined endogenous stem cell proliferation and angiogenesis in the ischemic rat brain after the transplantation of human neural stem cells. Focal cerebral ischemia in the rat brain was induced by middle cerebral artery occlusion. Human neural stem cells were transplanted into the subventricular zone. The behavioral performance of human neural stem cells-treated ischemic rats was significantly improved and cerebral infarct volumes were reduced compared to those in untreated animals. Numerous transplanted human neural stem cells were alive and preferentially localized to the ipsilateral ischemic hemisphere. Furthermore, 5-bromo-2′-deoxyuridine-labeled endogenous neural stem cells were observed in the subventricular zone and hippocampus, where they differentiated into cells immunoreactive for the neural markers doublecortin, neuronal nuclear antigen NeuN, and astrocyte marker glial fibrillary acidic protein in human neural stem cells-treated rats, but not in the untreated ischemic animals. The number of 5-bromo-2′-deoxyuridine-positive ⁄ anti-von Willebrand factor-positive proliferating endothelial cells was higher in the ischemic boundary zone of human neural stem cells-treated rats than in controls. Finally, transplantation of human neural stem cells in the brains of rats with focal cerebral ischemia promoted the proliferation of endogenous neural stem cells and their differentiation into mature neural-like cells, and enhanced angiogenesis. This study provides valuable insights into the effect of human neural stem cell transplantation on focal cerebral ischemia, which can be applied to the development of an effective therapy for stroke.

Key words: nerve regeneration, focal cerebral ischemia, middle cerebral artery occlusion, human neural stem cells, transplantation, differentiation, infarct size, behavioral analysis, endogenous neurogenesis, angiogenesis, rats, neural regeneration