Extracellular Vesicles Released from Human Umbilical Cord Derived Mesenchymal Stromal Cells Prevent Life Threatening Acute Graft Versus Host Disease in a Mouse Model of Allogeneic Hematopoietic Stem Cell Transplantation.
Mesenchymal stromal cells (MSCs) are attractive agents for the prophylaxis of acute graft versus host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo HSCT) However, safety concerns remain about their clinical application. In this study, we explored whether extracellular vesicles released from human umbilical cord derived MSCs (hUC MSC EVs) could prevent aGVHD in a mouse model of allo HSCT. hUC MSC EVs were intravenously administered to recipient mice on days 0 and 7 after allo HSCT, and the prophylactic effects of hUC MSC EVs were assessed by observing the in vivo manifestations of aGVHD, histologic changes in target organs, and recipient mouse survival. We evaluated the effects of hUC MSC EVs on immune cells and inflammatory cytokines by flow cytometry and ProcartaPlex(tm) Multiplex Immunoassays, respectively. The in vitro effects of hUC MSC EVs were determined by mitogen induced proliferation assays. hUC MSC EVs alleviated the in vivo manifestations of aGVHD and the associat.