Transplanted human iPSC-derived vascular endothelial cells promote functional recovery by recruitment of regulatory T cells to ischemic white matter in the brain

Ischemic stroke in the brain's white matter causes demyelination and neuroinflammation. Regulatory T cells (Tregs) infiltrate the ischemic brain, modulating inflammation. This study investigated whether transplanting human induced pluripotent stem cell-derived vascular endothelial cells (iVECs) improves white matter infarcts by influencing Tregs. iVECs and Tregs were transplanted into ischemic white matter. Fingolimod (FTY720), which sequesters lymphocytes in lymph nodes, was used to assess the role of peripheral immune cells. iVEC transplantation reduced inflammatory cells and CD4+ T cells while increasing Tregs. FTY720 suppressed neuroinflammation but not remyelination. iVEC transplantation increased Tregs from the periphery, and this Treg recruitment was crucial for remyelination. Transplanting Tregs with iVECs in FTY720-treated animals significantly improved myelin regeneration.

Bin Xu, Hiroya Shimauchi-Ohtaki, Yuhei Yoshimoto, Tetsushi Sadakata, Yasuki Ishizaki