Wednesday, April 10, 2013

The Effect of Rabbit Anti-Thymocyte Globulin on Human Mesenchymal Stem Cells

Background : Mesenchymal stem cells (MSCs) possess immunomodulatory properties which are of key interest for their application in autoimmunity and transplantation. In transplantation, administration of MSCs has shown promising results in preclinical models and has recently moved to clinical trials. Therefore it is important to study the interactions between MSCs and immunosuppressive drugs currently used in transplantation. We aimed to analyze the effect of rabbit anti-thymocyte globulin (rATG) MSCs.
Methods : MSCs were obtained from perirenal fat of kidney donors and exposed to ranging doses of rATG (Thymoglobulin®, Genzyme;0.5ug/ml-100ug/ml). Binding of rATG, effects on viability and susceptibility to be killed by cytotoxic lymphocytes as well as effects on their immunosuppressive potential of MSCs were tested.
Results : rATG binds dose-dependently to MSCs. This binding was associated with slightly impaired viability after 48 and 72 hours when compared to non-exposed MSCs. In contrast to non-treated MSCs, rATG pre-exposed MSCs were susceptible to be lysed by cytokine-activated CD8+ cytotoxic cells and NKT cells. The capacity of MSCs to suppress the proliferation of anti-CD3/CD28 activated CD4 and CD8 T cells was reduced by the presence of rATG in the culture.
Conclusion : rATG reduces the viability and anti-proliferative capacity of MSCs in a dose dependent manner and converts them into targets for CD8 T cells and NKT cell lysis (read more) Print this post

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