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Cell Therapy for Parkinson’s Disease: A Translational Approach to Assess the Role of Local and Systemic Immunosuppression

2016; Elsevier BV; Volume: 16; Issue: 7 Linguagem: Inglês

10.1111/ajt.13704

1600-6143

Romina Aron Badin, Marta Vadori, Bernard Vanhove, Véronique Nerrière‐Daguin, Philippe Naveilhan, Isabelle Neveu, C. Jan, Xavier Lévêque, Éric Venturi, Pascal Mermillod, Nadja Van Camp, Frédéric Dollé, Martine Guillermier, Luca Denaro, Renzo Manara, Valentina Citton, Paolo Simioni, Paolo Zampieri, Domenico D’Avella, Domenico Rubello, F Fante, M Boldrin, Giulia Maria De Benedictis, Laura Cavicchioli, Dino Sgarabotto, Mario Plebani, Annalisa Stefani, P. Brachet, Gilles Blancho, Jean‐Paul Soulillou, Philippe Hantraye, Emanuele Cozzi,

Neurogenesis and neuroplasticity mechanisms

Neural transplantation is a promising therapeutic approach for neurodegenerative diseases; however, many patients receiving intracerebral fetal allografts exhibit signs of immunization to donor antigens that could compromise the graft. In this context, we intracerebrally transplanted mesencephalic pig xenografts into primates to identify a suitable strategy to enable long-term cell survival, maturation, and differentiation. Parkinsonian primates received WT or CTLA4-Ig transgenic porcine xenografts and different durations of peripheral immunosuppression to test whether systemic plus graft-mediated local immunosuppression might avoid rejection. A striking recovery of spontaneous locomotion was observed in primates receiving systemic plus local immunosuppression for 6 mo. Recovery was associated with restoration of dopaminergic activity detected both by positron emission tomography imaging and histological examination. Local infiltration by T cells and CD80/86+ microglial cells expressing indoleamine 2,3-dioxigenase were observed only in CTLA4-Ig recipients. Results suggest that in this primate neurotransplantation model, peripheral immunosuppression is indispensable to achieve the long-term survival of porcine neuronal xenografts that is required to study the beneficial immunomodulatory effect of local blockade of T cell costimulation.