Bone Marrow-derived Mesenchymal Stem Cells Decrease Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cells Transplantation

Abstract

Graft-versus-host disease is a major complication of allogeneic hematopoietic stem cells transplantation, leading to serious morbidity and mortality. Mesenchymal stem cells(MSC)from bone marrow cause immunoregulation in vitro and in vivo. They also have the potential to protect from lethal GVHD after both autologous and allogeneic Hematopoietic Stem Cells Transplantation (HSCT). In this study, we investigated the mechanisms responsible for GVHD in the allo-HSCT co-transplantation with MSC condition. The model of acute GVHD in Rats was established using allogeneic HSC with donor-derived T cells transplantation, with or without additional donor-derived MSC co-transplantation. The degrees of GVHD were compared, the differentiation of CD4+, CD8+, Th1/Th2 and CD4+CD25+ T cells in vivo were assessed by flow cytometry and RT-PCR analyses. We found that MSC inhibited lethal GVHD after allo-HSCT. The value of CD8+ and CD4+ T cells and the ratio of Th1/Th2 T cell subsets decreased, at the same time the proportion of CD4+CD25+ T cells increased both in spleen lymphocytes and thymocytes in vivo after allo-HSCT with MSC co-transplantation compared with conventional allo-HSCT. Our results strongly suggested that BM-derived MSC has the function of preventing lethal GVHD after allo-HSCT by means of homeostasis of T subsets in vivo.

Inhibitory effect of CXC chemokine receptor 4 antagonist AMD3100 on bleomycin induced murine pulmonary fibrosis

“…After 10 6 cells were plated in Ø100 mm culture dish, cells were incubated with DMEM/F-12 media containing 20% FBS, 200 IU/ml penicillin and 250 μg/ml streptomycin for 48 h. The HSCs were purified from nonadherent cells after removing the RBCs by using the distilled water and adherent cells were collected as MSCs. The purified BMDMSC was identified by CD 44 staining (Tian et al, 2008) and BMDHSC was identified by CD45 staining. The fourth to sixth passages were used for individual chemotactic experiments.…”

Mesenchymal Stem Cells – An Oversimplified Nomenclature for Extremely Heterogeneous Progenitors

“…At present, three major fi elds can be identi fi ed, in which MSC can and will be used for therapeutic purposes: (I) tissue repair Mazhari and Hare 2007 ;Müller et al 2008b ) ; (II) therapy of chronic graft vs. host disease (GvHD) (Aksu et al 2008 ;Le Blanc et al 2008 ;Tian et al 2008 ) , and (III) enhancement of hematopoietic stem cell engraftment in an allogeneic transplant setting Müller et al 2008a ) . The underlying key mechanism in all the three fi elds is not completely understood, but probably a result of MSC-induced immunosuppression.…”

Modified Bone Marrow Stromal Cells Therapy for Central Nervous System Disorders

“…It is popular attended as appropriate seed cells [5,6]. There were increasing evidences that transplanted BMSCs significantly promote nervous functional recovery after Central Nervous System (CNS) injured in the animal models [7][8][9]. The BMSCs treatment for neural disease would be of great benefit, but the mechanism is still unclear [6,10,11].…”