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

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 G...

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Main Authors: Oral Nevruz, Ferit Avcu, A. Uğur Ural, Aysel Pekel, Bahar Dirican, Mükerrem Safalı, Elvin Akdağ, Murat Beyzadeoğlu, Tayfun İde, Ali Sengül
Format: Article
Language:English
Published: Galenos Publishing House 2013-09-01
Series:Turkish Journal of Hematology
Subjects:
Online Access:https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-02223
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author Oral Nevruz
Ferit Avcu
A. Uğur Ural
Aysel Pekel
Bahar Dirican
Mükerrem Safalı
Elvin Akdağ
Murat Beyzadeoğlu
Tayfun İde
Ali Sengül
author_facet Oral Nevruz
Ferit Avcu
A. Uğur Ural
Aysel Pekel
Bahar Dirican
Mükerrem Safalı
Elvin Akdağ
Murat Beyzadeoğlu
Tayfun İde
Ali Sengül
author_sort Oral Nevruz
collection DOAJ
description 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.
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spelling doaj.art-9a8ed90f873140c5bd59808abdf7c1352023-02-15T16:09:16ZengGalenos Publishing HouseTurkish Journal of Hematology1308-52632013-09-0130325626210.4274/Tjh.2013.0032TJH-02223Immunosuppressive Effects of Multipotent Mesenchymal Stromal Cells on Graft-Versus-Host Disease in Rats Following Allogeneic Bone Marrow TransplantationOral Nevruz0Ferit Avcu1A. Uğur Ural2Aysel Pekel3Bahar Dirican4Mükerrem Safalı5Elvin Akdağ6Murat Beyzadeoğlu7Tayfun İde8Ali Sengül9Gülhane Medical Academy, Department Of Hematology, Ankara, TurkeyGülhane Medical Academy, Department Of Hematology, Ankara, TurkeyGülhane Medical Academy, Department Of Hematology, Ankara, TurkeyGülhane Medical Academy, Department Of Immunology, Ankara, TurkeyGülhane Medical Academy, Department Of Radiation Oncology, Ankara, TurkeyGülhane Medical Academy, Department Of Pathology, Ankara, TurkeyGülhane Medical Academy, Department Of Medical Oncology Research Center, Ankara, TurkeyGülhane Medical Academy, Department Of Radiation Oncology, Ankara, TurkeyGülhane Medical Academy, Department Of Medical Oncology Research Center, Ankara, TurkeyGülhane Medical Academy, Department Of Immunology, Ankara, TurkeyObjective: 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.https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-02223mezenchimal stromal cellbone marrow transplantationi̇mmunsupresion
spellingShingle Oral Nevruz
Ferit Avcu
A. Uğur Ural
Aysel Pekel
Bahar Dirican
Mükerrem Safalı
Elvin Akdağ
Murat Beyzadeoğlu
Tayfun İde
Ali Sengül
Immunosuppressive Effects of Multipotent Mesenchymal Stromal Cells on Graft-Versus-Host Disease in Rats Following Allogeneic Bone Marrow Transplantation
Turkish Journal of Hematology
mezenchimal stromal cell
bone marrow transplantation
i̇mmunsupresion
title Immunosuppressive Effects of Multipotent Mesenchymal Stromal Cells on Graft-Versus-Host Disease in Rats Following Allogeneic Bone Marrow Transplantation
title_full Immunosuppressive Effects of Multipotent Mesenchymal Stromal Cells on Graft-Versus-Host Disease in Rats Following Allogeneic Bone Marrow Transplantation
title_fullStr Immunosuppressive Effects of Multipotent Mesenchymal Stromal Cells on Graft-Versus-Host Disease in Rats Following Allogeneic Bone Marrow Transplantation
title_full_unstemmed Immunosuppressive Effects of Multipotent Mesenchymal Stromal Cells on Graft-Versus-Host Disease in Rats Following Allogeneic Bone Marrow Transplantation
title_short Immunosuppressive Effects of Multipotent Mesenchymal Stromal Cells on Graft-Versus-Host Disease in Rats Following Allogeneic Bone Marrow Transplantation
title_sort immunosuppressive effects of multipotent mesenchymal stromal cells on graft versus host disease in rats following allogeneic bone marrow transplantation
topic mezenchimal stromal cell
bone marrow transplantation
i̇mmunsupresion
url https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-02223
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AT feritavcu immunosuppressiveeffectsofmultipotentmesenchymalstromalcellsongraftversushostdiseaseinratsfollowingallogeneicbonemarrowtransplantation
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AT bahardirican immunosuppressiveeffectsofmultipotentmesenchymalstromalcellsongraftversushostdiseaseinratsfollowingallogeneicbonemarrowtransplantation
AT mukerremsafalı immunosuppressiveeffectsofmultipotentmesenchymalstromalcellsongraftversushostdiseaseinratsfollowingallogeneicbonemarrowtransplantation
AT elvinakdag immunosuppressiveeffectsofmultipotentmesenchymalstromalcellsongraftversushostdiseaseinratsfollowingallogeneicbonemarrowtransplantation
AT muratbeyzadeoglu immunosuppressiveeffectsofmultipotentmesenchymalstromalcellsongraftversushostdiseaseinratsfollowingallogeneicbonemarrowtransplantation
AT tayfunide immunosuppressiveeffectsofmultipotentmesenchymalstromalcellsongraftversushostdiseaseinratsfollowingallogeneicbonemarrowtransplantation
AT alisengul immunosuppressiveeffectsofmultipotentmesenchymalstromalcellsongraftversushostdiseaseinratsfollowingallogeneicbonemarrowtransplantation