Human iPSC ‐derived endothelial cells promote CNS remyelination via BDNF and mTORC1 pathway

Dan Ma*, Huiyuan Zhang, Le Yin, Hao Xu, Lida Wu, Rahul Shaji, Fatema Rezai, Ayesha Mulla, Sukhteerath Kaur, Shengjiang Tan, Boris Kysela, Yilong Wang, Zhiguo Chen, Chao Zhao*, Yuchun Gu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Damage of myelin is a component of many diseases in the central nervous system (CNS). The activation and maturation of the quiescent oligodendrocyte progenitor cells (OPCs) are the crucial cellular processes for CNS remyelination, which is influenced by neuroinflammation in the lesion microenvironment. Endothelial cells derived from human induced pluripotent stem cells (hiPSC‐ECs) have shown promise in restoring function in various preclinical animal models. Here we ask whether and whether transplantation of hiPSC‐ECs could benefit remyelination in a mouse model of CNS demyelination. Our results show that in vitro, hiPSC‐ECs increase OPC proliferation, migration and differentiation via secreted soluble factors including brain‐derived neurotrophic factor (BDNF). hiPSC‐ECs also promote the survival of oligodendrocyte lineage cells in vitro and in vivo. Transplantation of hiPSC‐ECs into a toxin‐induced demyelination lesion in mouse corpus callosum (CC) leads to increased density of oligodendrocyte lineage cells and level of myelin in demyelinated area, correlated with a decreased neuroinflammation and an increased proportion of pro‐regenerative M2 phenotype in microglia/macrophages. The hiPSC‐EC‐exposed oligodendrocyte lineage cells showed significant increase in the level of phosphorylated S6 ribosomal protein (pS6) both in vitro and in vivo, indicating an involvement of mTORC1 pathway. These results suggest that hiPSC‐ECs may benefit myelin protection and regeneration which providing a potential source of cell therapy for a wide range of diseases and injuries associated with myelin damage.
Original languageEnglish
Pages (from-to)133-155
Issue number1
Early online date7 Sept 2023
Publication statusPublished - Jan 2024

Bibliographical note

Copyright © 2023 The Authors. GLIA published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License [], which permits use, distribution and reproduction in any medium,provided the original work is properly cited.

Funding Information:
This work was supported by Aston University to Dan Ma and Royal Society‐Newton Advanced Fellowship to Zhiguo Chen and Chao Zhao (NA150482). The authors thank Dr. Daniel Morrison from University of Cambridge and Dr. David Nagel from Aston University for scientific and technical support. The authors also thank Chris Brown from University of Cambridge, Matthew Crossley and Wayne Fleary from Aston University for research facility work.


  • oligodendrocyte
  • iPSC
  • endothelial cell
  • BDNF
  • mTORC1
  • neuroinflammation
  • remyelination


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