A Study Of Haploidentical Mesenchymal Stem Cells And Hematopoietic Stem Cell Co-transplantation With Nonmyeloablative Conditioning In Rhesus Model

The major problems of haploidentical stem cell transplantation are those of intractable of graft versus host disease (GVHD), graft rejection and high infection-related mortality etc, because of MHC barrier. Recently, nonmyeloablative hematopoietic stem cell transplantation (NST) was reported ameliorating GVHD by establishment of mixed chimerism to induce transplantation tolerance. Mesenchymal stem cells (MSCs) are an important cell population in bone marrow microenvironment, are capable of differentiating to bone marrow stromal cells, and are mainly engaged in supporting hematopoiesis. Recent studies showed that MSCs could also enhance allogeneic hematopoietic engraftment and lessen GVHD. The purpose of this study was to test if haploidentical MSCs and hematopoietic stem cell co-transplantation with nonmyleoablative conditioning would be of benefits to haploidentical transplantation.First we isolated and cultured rhesus MSCs from bone marrow, and studied its phenotype and biological characteristics, then examined the safty of MSCs tansplantation, There were not significant toxicity when MSCs were administered intravenously or intra-bone marrow, and MSCs were capable of homing to and establishing residence within the recipient's bone marrow.Next parent rhesus monkeys were used as donors, offspring rhesus as recipients, then they were divided into two group, NST group (4 couples) and MSCs+NST group (4 couples), hematopoietic recovery, chimerism level, GVHD were assessed regularly. In NST group, hematopoietic recovery were rapid (+8d), chimerism analysis showed full donor chimerism (FDC) in two of four rhesuses, and II to III acute GVHD developed, transplantation exclusion occurred in one rhesus. In MSCs+NST group, chimerism analysis showed full donor chimerism (FDC) in one of rhesuses, hematopoietic recovery were rapid (+8d), and II to III acute GVHD developed; in another two of four rhesuses, chimerism analysis showed mixed chimerism converting to full donor chimerism (FDC) gradually and hematopoietic recovery were slow(+13d); no GVHD developed.All above experiments demonstrated that MSCs and NST could enhance allogeneic hematopoietic engraftment and lessen GVHD, maybe a new approach in haploidentical...