Immunosuppressive Effects of Multipotent Mesenchymal Stromal Cells on Graft-Versus-Host Disease in Rats Following Allogeneic Bone Marrow Transplantation

Oral Nevruz,Bahar Dirican,A Uğur Ural,Elvin Akdağ,Mükerrem Safalı,Ali Sengül,Ferit Avcu,Tayfun İde,Murat Beyzadeoğlu,Aysel Pekel

doi:10.4274/tjh.2013.0032

Abstract

Objective: Graft-versus-host disease (GVHD) is a major obstacle to successful allogeneic bone marrow transplantation (allo-BMT). While multipotent mesenchymal stromal cells (MSCs) demonstrate alloresponse in vitro and in vivo, they also have clinical applications toward prevention or treatment of GVHD. The aim of this study was to investigate the ability of MSCs to prevent or treat GVHD in a rat BMT model. Materials and Methods: The GVHD model was established by transplantation of Sprague Dawley rats’ bone marrow and spleen cells into lethally irradiated (950 cGy) SDxWistar rat recipients. A total of 49 rats were randomly assigned to 4 study and 3 control groups administered different GVHD prophylactic regimens including MSCs. After transplantation, clinical GVHD scores and survival status were monitored. Results: All irradiated and untreated control mice with GVHD died. MSCs inhibited lethal GVHD as efficiently as the standard GVHD prophylactic regimen. The gross and histopathological findings of GVHD and the ratio of CD4/CD8 expression decreased. The subgroup given MSCs displayed higher in vivo proportions of CD25+ T cells and plasma interleukin-2 levels as compared to conventional GVHD treatment after allo-BMT. Conclusion: Our results suggest that clinical use of MSCs in both prophylaxis against and treatment of established GVHD is effective. This study supports the use of MSCs in the prophylaxis and treatment of GVHD after allo-BMT; however, large scale studies are needed. Conflict of interest:None declared.

Highlights

Allogeneic hematopoietic stem cell transplantation after high-dose marrow-ablative chemoradiotherapy is an effective treatment method in various hematologic, neoplastic, and congenital disorders
Our results suggest that clinical use of mesenchymal stromal cells (MSCs) in both prophylaxis against and treatment of established graft-versus-host disease (GVHD)
This study supports the use of MSCs in the prophylaxis and treatment of GVHD after allo-BMT; large scale studies are needed

Summary

Introduction

Allogeneic hematopoietic stem cell transplantation (alloHSCT) after high-dose marrow-ablative chemoradiotherapy is an effective treatment method in various hematologic, neoplastic, and congenital disorders. The interest in MSC therapy has been raised by the observation that MSCs are able to modulate immune responses in vitro and in vivo [6]. MSCs have been reported to induce T cell division arrest, to inhibit the differentiation and maturation of dendritic cells, and to decrease the production of inflammatory cytokines by various immune cell populations [8,9,10]. These properties can be utilized in the context of allo-HSCT, to modulate GVHD and graft rejection [6]. MSCs can be thought of as promising agents for severe steroid-resistant acute GVHD and nonresponders can be treated with alternative methods, including MSCs (11)

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Discussion

Conclusion