Complement lysis affects engraftment and efficacy of human mesenchymal stromal cell-based therapy

Acute Graft-versus-Host-Disease (aGVHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). Transplantation of immunosuppressive human mesenchymal stromal cells (hMSCs) can protect against aGVHD post HSCT; however, their efficacy is limited by poor engraftment and survival. Moreover, infused MSCs can be damaged by activated complement, yet strategies to minimise complement injury of hMSCs and improve their survival are limited. Here, we report that hMSCs derived from three tissues divergently protected against aGVHD in a mouse model of this disease. Adipose tissue (AT)-hMSCs preferentially suppressed complement in vitro and in vivo, resisted complement lysis and survived better after transplantation when compared to bone marrow (BM)- and umbilical cord (UC)-hMSCs. AT-hMSCs also prolonged survival and improved the symptoms and pathological features of aGVHD. Comparative gene expression profiling analysis of RNA-seq data for different sources of Mesenchymal stem cells (MSCs) cells.