Artikel
Immunomodulation with adipose and bone marrow-derived mesenchymal stem cells prolongs graft survival in vascularized composite allotransplantation
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Veröffentlicht: | 3. September 2014 |
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Gliederung
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Background: Since VCAs are life-enhancing and not life-saving, there is an utmost interest in reducing long-term immunosuppression. Mesenchymal stromal cells have shown immunomodulatory properties. Herein we compare adipose-derived and bone marrow-derived mesenchymal stromal cells in terms of dosage and efficacy in a rat hindlimb transplantation model.
Methods: AD-MSCs and BM-MSCs were isolated, cultured and characterized. Cells from both sources were tested distinctly for immunosuppressive function in mixed lymphocyte reaction (MLR) assays. Lewis rat recipients received mismatched Brown-Norway hindlimb transplants. For the assessment on allograft survival rats were injected either AD-MSCs or BM-MSCs (1x106 or 5x106 cells/animal) systemically. Immunosuppression was withdrawn after 3 weeks. In vivo Treg induction and peripheral blood chimerism and microchimerism in lymphatic organs was analyzed.
Results: Both AD-MSCs and BM-MSCs exhibited immunosuppressive function in vitro. While all animals revealed peripheral multi-lineage chimerism at 4 weeks and upregulation of regulatory T-cells, these findings were only transient. Nevertheless >50% of the animals showed long-term acceptance of the transplanted hindlimb beyond 120 days. These findings correlated to microchimerism in the bone marrow and spleen.
Conclusion: Our results confirm that AD-MSCs and BM-MSCs exert immunomodulatory function. It remains unclear if paracrine effects as an important function of MSCs are also involved in tolerogenic and immunomodulatory effects in transplantation.