Human Allogeneic Bone Marrow and Adipose Tissue Derived Mesenchymal Stromal Cells Induce CD8+ Cytotoxic T Cell ReactivityMarieke Roemeling-van Rhijn1, Marlies E Reinders3, Marcella Franquesa1, Anja U Engela1, Sander S Korevaar1, Helene Roelofs4, Jan NM IJzermans2, Michiel GH Betjes1, Carla C Baan1, Willem Weimar1 and Martin J Hoogduijn1
- Corresponding Author:
- Marieke Roemeling-van Rhijn
Erasmus University Medical Center
Transplant Laboratory Internal Medicine
Room Na-319, P.O.box 2040, 3000 CA Rotterdam, The Netherlands
Tel: +31 (0)10-7035421
E-mail: [email protected]
Received Date: November 20, 2013; Accepted Date: December 10, 2013; Published Date: December 12, 2013
Citation: Roemeling-van Rhijn, Reinders ME, Franquesa M, Engela AU, Korevaar SS, et al. (2013) Human Allogeneic Bone Marrow and Adipose Tissue Derived Mesenchymal Stromal Cells Induce CD8+ Cytotoxic T Cell Reactivity. J Stem Cell Res Ther S6:004. doi:10.4172/2157-7633.S6-004
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.
Introduction: For clinical applications, Mesenchymal Stromal Cells (MSC) can be isolated from bone marrow and adipose tissue of autologous or allogeneic origin. Allogeneic cell usage has advantages but may harbor the risk of sensitization against foreign HLA. Therefore, we evaluated whether bone marrow and adipose tissue-derived MSC are capable of inducing HLA-specific alloreactivity. Methods: MSC were isolated from healthy human Bone Marrow (BM-MSC) and adipose tissue (ASC) donors. Peripheral Blood Mononuclear Cells (PBMC) was co-cultured with HLA-AB mismatched BM-MSC or ASC precultured with or without IFNy. After isolation via FACS sorting, the educated CD8+ T effector populations were exposed for 4 hours to Europium labeled MSC of the same HLA make up as in the co-cultures or with different HLA. Lysis of MSC was determined by spectrophotometric measurement of Europium release. Results: CD8+ T cells educated with BM-MSC were capable of HLA specific lysis of BM-MSC. The maximum lysis was 24% in an effector:target (E:T) ratio of 40:1. Exposure to IFNγ increased HLA-I expression on BM-MSC and increased lysis to 48%. Co-culturing of PBMC with IFNγ-stimulated BM-MSC further increased lysis to 76%. Surprisingly, lysis induced by ASC was significantly lower. CD8+ T cells educated with ASC induced a maximum lysis of 13% and CD8+ T cells educated with IFNγ-stimulated ASC of only 31%. Conclusion: Allogeneic BM-MSC, and to a lesser extend ASC, are capable of inducing HLA specific reactivity. Our results suggest that clinical therapy with allogeneic MSC should be carefully considered.