Human Bone Marrow- and Adipose Tissue-derived Mesenchymal Stromal Cells are Immunosuppressive In vitro and in a Humanized Allograft Rejection ModelMarieke Roemeling-van Rhijn1*, Meriem Khairoun2, Sander S Korevaar1, Ellen Lievers2, Danielle G Leuning2, Jan NM IJzermans3, Michiel GH Betjes1, Cees van Kooten2, Hans JW de Fijter2, Ton J Rabelink2, Carla C Baan1 , Willem Weimar1, Helene Roelofs4, Martin J Hoogduijn1 and Marlies E Reinders2
- Corresponding Author:
- Marieke Roemeling-van Rhijn
Erasmus University Medical Center
Transplant Laboratory Internal Medicine Room No: 319
P.O. box 2040 3000 CA Rotterdam, The Netherlands
E-mail: [email protected]
Received Date: November 06, 2013; Accepted Date: November 22, 2013; Published Date: November 25, 2013
Citation: Roemeling-van Rhijn, Khairoun M, Korevaar SS, Lievers E, Leuning DG, et al. (2013) Human Bone Marrow-and Adipose Tissue-derived Mesenchymal Stromal Cells are Immunosuppressive In vitro and in a Humanized Allograft Rejection Model. J Stem Cell Res Ther S6:001. doi:10.4172/2157-7633.S6-001
Copyright: © 2013 Roemeling-van Rhijn, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: Recent studies with bone marrow (BM)-derived Mesenchymal Stromal Cells (MSC) in transplant recipients demonstrate that treatment with MSC is safe and clinically feasible. While BM is currently the preferred source of MSC, adipose tissue is emerging as an alternative. To develop efficient therapies, there is a need for preclinical efficacy studies in transplantation. We used a unique humanized transplantation model to study the in vivo immunosuppressive effect of human BM-MSC and adipose tissue-derived MSC (ASC).
Methods: Gene expression of BM-MSC and ASC and their capacity to inhibit activated PBMC proliferation was evaluated. The in vivo immunosuppressive effect of BM-MSC and ASC was studied in a humanized mouse model. SCID mice were transplanted with human skin grafts and injected with human allogeneic PBMC with or without administration of BM-MSC or ASC. The effect of MSC on skin graft rejection was studied by immunohistochemistry and PCR.
Results: BM-MSC and ASC expressed TGFβ, CXCL-10 and IDO. IDO expression and acitivity increased significantly in BM-MSC and ASC upon IFN-γ stimulation. IFN-γ stimulated BM-MSC and ASC inhibited the proliferation of activated PBMC in a significant and dose dependent manner. In our humanized mouse model, alloreactivity was marked by pronounced CD45+ T-cell infiltrates consisting of CD4+ and CD8+ T cells and increased IFN-γ expression in the skin grafts which were all significantly inhibited by both BM-MSC and ASC. Conclusion: BM-MSC and ASC are immunosuppressive in vitro and suppress alloreactivity in a preclinical humanized transplantation model.