Mesenchymal Stromal Cells Fail to Alleviate Experimental Graft-Versus-Host Disease in Rats Transplanted with Major Histocompatibility Complex-Mismatched Bone Marrow

摘要: Mesenchymal stromal cells (MSC) can be used to treat graft-versus-host disease (GVHD) caused by allogeneic stem cell transplantation (allo-SCT). The effectiveness of this therapy has been variable in clinical trials and experimental animal models. In study, we investigated the ability bone marrow (BM)-derived MSC alleviate GVHD an rat model allo-SCT using two different combinations major histocompatibility complex (MHC) mismatch with survival as primary endpoint. Recipient rats received total body irradiation a transplant T cell-depleted donor BM either full [PVG.7B → BN] or partial MHC [PVG.1U PVG.R23] restricted class II non-classical I sub-regions (RT1-B/D-CE/N/M). was invoked infusion graded doses leukocytes 2 weeks after allo-SCT. Weekly were injected starting on day leukocyte infusion. No significant overall improvement mortality morbidity observed settings. Stimulation exogenous tumor necrosis factor α interferon (IFN)γ prior could not rescue BM-transplanted from lethal acute GVHD. conclusion, repeated administrations failed fully partially MHC-mismatched rat.