Transpl Int. 2013 Jun;26(6):651-8.

The effect of rabbit antithymocyte globulin on human mesenchymal stem cells.

Marcella Franquesa1,2, Carla C. Baan1,  Sander S. Korevaar1, Anja U. Engela1, Marieke Roemeling-van Rhijn1, Willem Weimar1, Michiel G. H. Betjes1, Josep M. Grinyo2 and Martin J. Hoogduijn1

1 Transplantation Laboratory, Internal Medicine, Erasmus MC, Rotterdam, the Netherlands

2 Experimental Nephrology and Nephrology Department, Bellvitge Hospital-UB-IDIBELL, Barcelona, Spain

 

Abstract

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 antithymocyte globulin (rATG) MSCs. MSCs were obtained from perirenal fat of kidney donors and exposed to ranging doses of rATG (Thymoglobulin, Genzyme; 0.5–100 lg/ 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. rATG binds dose-dependently to MSCs. This binding was associated with slightly impaired viability after 48 and 72 h when compared with nonexposed MSCs. In contrast to nontreated MSCs, rATG preexposed 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 were reduced by the presence of rATG in the culture. rATG reduces the viability and antiproliferative capacity of MSCs in a dose-dependent manner and converts them into targets for CD8 T cells and NKT cell lysis.

PMID: 23682671

 

Supplement

Mesenchymal stem cells (MSC) are adult derived pluripotent cells which can be found and virtually any tissue. They have been widely studied for their potential regenerative capacity and proved Immunomodulatory ability that makes them promising candidate for the treatment of autoimmune diseases and transplantation.

In this study we focused in adipose tissue-derived MSC obtained in the moment of surgery from kidney transplant donors. The fat tissue was mechanically and enzymatically disrupted to obtain a unicellular suspension that was plated in culture flasks to further obtain and expand the specific MSC population (grow by plastic adherence and fibroblastic morphology) Figure 1.

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M. Franquesa-2

Figure1: Isolation and expansion of Adipose tissue derived MSC.

Our main interest is the clinical application of MSC in kidney transplant patients as a immunosuppressive therapy Figure 2. As the field moves forward and already 4 clinical trials have been published, one of the main concerns to be addressed is the effect of concomitantly used immunosuppressive drugs on the Immunomodulatory capacity of MSC.

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Figure 2: Immunomodulatory properties of MSC. Franquesa et al Curr Opin Organ Transplant 2012, 17:355–361

 

The results obtained indicate  that the concomitant administration of MSC with the depleting drug rabbit Anti-Thymocyte Globuline (rATG) decreases the immunossuppressive capacity of MSC. Therefore we recommend the administration of MSC before or after the depleting agent rATG.

 

Contact:

Marcella Franquesa, PhD

Post-doctoral Researcher

Internal Medicine

Nephrology and Transplantation

P.O. Box 2040, 3000 CA Rotterdam, The Netherlands

Visiting address: Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands, room Na523

m.franquesa@erasmusmc.nl

www.erasmusmc.nl

M. Franquesa-4

 

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