Supplementing mesenchymal stem cells improves the therapeutic effect of hematopoietic stem cell transplantation in the treatment of murine systemic lupus erythematosus

摘要

Transplantation of hematopoietic stem cells (HSCs) has been demonstrated to be a promising strategy in the treatment of systemic lupus erythematosus (SLE). Mesenchymal stem cells (MSCs) support hematopoiesis of HSCs and suppress immune response in a dose-dependent manner. Previous study showed that MSCs could alleviate the pathologic conditions of MRL/lpr mice (SLE animal model) when cotransplanted with bone marrow cells. Here, we investigated whether MSCs could improve the therapeutic effect of HSC transplantation in treating MRL/lpr mice in a dose-dependent manner. We found that lethally irradiated MRL/lpr mice were successfully reconstituted with HSCs alone or with various amounts of MSCs. Mice transplanted with HSCs and MSCs in the ratios of 5:1 (HSCs:MSCs) showed less transfusion-associated graft-versus-host reaction, steady body weight, and improved renal functions when compared with mice transplanted with HSCs only and those cotransplanted with MSCs in lower ratios. These results suggest that supplementing MSCs can improve the therapeutic effect of HSC transplantation in treatment of MRL/lpr mice in a dose-dependent manner.