Local control of the host immune response performed with mesenchymal stem cells: perspectives for functional intracerebral xenotransplantation

Journal of Cellular and Molecular Medicine

Xavier Lévêque¹  Elodie Mathieux¹  Véronique Nerrière-Daguin¹  Reynald Thinard¹  Laetitia Kermarrec²  Tony Durand²  Thomas Haudebourg¹  Bernard Vanhove¹  Laurent Lescaudron¹  Isabelle Neveu¹ 

[1] INSERM, UMR 1064, Nantes, France;INSERM, UMR 913, Nantes, France

关键词: immunosuppression;    rejection;    mesenchymal stem cells;    T cells;    Parkinson;    brain transplantation;    survival;    restorative strategies;   

DOI  :  10.1111/jcmm.12414

来源: Wiley

【 摘 要 】

Abstract

Foetal pig neuroblasts are interesting candidates as a cell source for transplantation, but xenotransplantation in the brain requires the development of adapted immunosuppressive treatments. As systemic administration of high doses of cyclosporine A has side effects and does not protect xenotransplants forever, we focused our work on local control of the host immune responses. We studied the advantage of cotransplanting syngenic mesenchymal stem cells (MSC) with porcine neuroblasts (pNb) in immunocompetent rat striata. Two groups of animals were transplanted, either with pNb alone or with both MSC and pNb. At day 63, no porcine neurons were detected in the striata that received only pNb, while four of six rats transplanted with both pNb and MSC exhibited healthy porcine neurons. Interestingly, 50% of the cotransplanted rats displayed healthy grafts with pNF70+ and TH+ neurons at 120 days post-transplantation. qPCR analyses revealed a general dwindling of pro- and anti-inflammatory cytokines in the striata that received the cotransplants. Motor recovery was also observed following the transplantation of pNb and MSC in a rat model of Parkinson's disease. Taken together, the present data indicate that the immunosuppressive properties of MSC are of great interest for the long-term survival of xenogeneic neurons in the brain.

【 授权许可】

CC BY   
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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