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Rescue of Brain Function Using Tunneling Nanotubes Between Neural Stem Cells and Brain Microvascular Endothelial Cells

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Abstract

Evidence indicates that neural stem cells (NSCs) can ameliorate cerebral ischemia in animal models. In this study, we investigated the mechanism underlying one of the neuroprotective effects of NSCs: tunneling nanotube (TNT) formation. We addressed whether the control of cell-to-cell communication processes between NSCs and brain microvascular endothelial cells (BMECs) and, particularly, the control of TNT formation could influence the rescue function of stem cells. In an attempt to mimic the cellular microenvironment in vitro, a co-culture system consisting of terminally differentiated BMECs from mice in a distressed state and NSCs was constructed. Additionally, engraftment experiments with infarcted mouse brains revealed that control of TNT formation influenced the effects of stem cell transplantation in vivo. In conclusion, our findings provide the first evidence that TNTs exist between NSCs and BMECs and that regulation of TNT formation alters cell function.

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Acknowledgments

This work was supported by the National Natural Science Foundations of China (81230027, 81070959, 81471219), the Outstanding Subject Leaders Project of Shanghai (14XD1403400), Technology Support Project of Shanghai (14140903300), and the Science Committee Animal Project of Shanghai (13140903400).

Conflicts of Interest

The authors of this manuscript have no conflicts of interest.

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Authors and Affiliations

  1. Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China

    Xiaoqing Wang, Chong Xie, Zijian Tan, Qi Tian, Desheng Zhu, Mingyuan Liu & Yangtai Guan

  2. Department of Geriatrics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China

    Xiaowen Yu

  3. Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China

    Yangtai Guan

Authors
  1. Xiaoqing Wang
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  2. Xiaowen Yu
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  3. Chong Xie
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  4. Zijian Tan
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  5. Qi Tian
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  6. Desheng Zhu
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  7. Mingyuan Liu
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  8. Yangtai Guan
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Corresponding authors

Correspondence to Mingyuan Liu or Yangtai Guan.

Additional information

Xiaoqing Wang and Xiaowen Yu devoted equally to this work.

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Wang, X., Yu, X., Xie, C. et al. Rescue of Brain Function Using Tunneling Nanotubes Between Neural Stem Cells and Brain Microvascular Endothelial Cells. Mol Neurobiol 53, 2480–2488 (2016). https://doi.org/10.1007/s12035-015-9225-z

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  • DOI: https://doi.org/10.1007/s12035-015-9225-z

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