Mitochondria Derived From iPSCs Control by Reciprocal Regulation of Th17/Treg and Anti-Fibrosis

Several studies have reported the immunoregulatory effects of transplanting mitochondria from mesenchymal stem cells. However, whether similar effects can be achieved using mitochondria derived from human induced pluripotent stem cells (iPSCs; iMito) has not yet been investigated. Here, we examined the protective effects of iMito in a dextran sodium sulfate (DSS)-induced colitis mouse model. To address this, we investigated the effects both in vitro and in vivo. First, iMitos were transferred into mouse splenocytes, and the expression and secretion of IL-17 and FoxP3 were measured. Next, iMitos were transferred into mice with inflammatory bowel disease (IBD) induced by DSS. Intestinal tissues were assessed histologically, and immune cell infiltration was measured. In vitro, iMitos transfer increased mitochondrial function, evidenced by higher ATP synthesis. An immunomodulatory effect was observed, with decreased IL-17 and increased FoxP3 expression. In vivo, iMitos transplantation in IBD mice led to improvements in body weight and intestinal tissue damage; it decreased Th17 cells, increased Tregs, and reduced inflammatory cytokines and fibrosis markers. These data suggest the therapeutic potential of iMitos in treating human inflammatory diseases.