Abstract
Neural stem/progenitor cells (NSPCs) are multi-potent cells defined by their ability to self-renew and differentiate into cells of glial and neuronal lineage. Because of these properties, NSPCs have been proposed as therapeutic tools to replace lost neurons. Recent observations in animal models of immune-related diseases indicate that NSPCs display immunomodulatory properties that might be a great interest for cell therapy. In particular, transplantation of NSPCs might be very useful as local immunosuppressive agent to promote the long-term survival of neuronal xenotransplant in the brain. To study this possibility, we have analysed the impact of NSPCs on anti-CD3/CD28-activated T cells. In vitro analyses clearly show that porcine, rat, and mouse NSPCs inhibit the proliferation of activated T cells. This result raises new perspectives concerning the use of NSPCs in cell therapy.
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References
Alvarez-Buylla, A., and Temple, S. (1998) Stem cells in the developing and adult nervous system. J. Neurobiol. 36, 105–110.
Svendsen, C. N., and Smith, A. G. (1999) New prospects for human stem-cell therapy in the nervous system. Trends Neurosci. 22, 357–364.
Martinez-Serrano, A., Rubio, F. J., Navarro, B., Bueno, C., and Villa, A. (2001) Human neural stem and progenitor cells: in vitro and in vivo properties, and potential for gene therapy and cell replacement in the CNS. Curr. Gene Ther. 1, 279–299.
Bjorklund, A., and Lindvall, O. (2000) Cell replacement therapies for central nervous system disorders. Nat. Neurosci. 3, 537–544.
Reynolds, B. A., Tetzlaff, W., and Weiss, S. (1992) A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. J. Neurosci. 12, 4565–4574.
Reynolds, B. A., and Weiss, S. (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255, 1707–1710.
Harrower, T. P., Tyers, P., Hooks, Y., and Barker, R. A. (2006) Long-term survival and integration of porcine expanded neural precursor cell grafts in a rat model of Parkinson’s disease. Exp. Neurol. 197, 56–69.
Smith, P. M., and Blakemore, W. F. (2000) Porcine neural progenitors require commitment to the oligodendrocyte lineage prior to transplantation in order to achieve significant remyelination of demyelinated lesions in the adult CNS. Eur. J. Neurosci. 12, 2414–2424.
Karbanova, J., Mokry, J., and Kotingova, L. (2004) Neural stem cells transplanted into intact brains as neurospheres form solid grafts composed of neurons, astrocytes and oligodendrocyte precursors. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub. 148, 217–220.
Einstein, O., Fainstein, N., Vaknin, I., Mizrachi-Kol, R., Reihartz, E., Grigoriadis, N., Lavon, I., Baniyash, M., Lassmann, H., and Ben-Hur, T. (2007) Neural precursors attenuate autoimmune encephalomyelitis by peripheral immunosuppression. Ann. Neurol. 61, 209–218.
Einstein, O., Grigoriadis, N., Mizrachi-Kol, R., Reinhartz, E., Polyzoidou, E., Lavon, I., Milonas, I., Karussis, D., Abramsky, O., and Ben-Hur, T. (2006) Transplanted neural precursor cells reduce brain inflammation to attenuate chronic experimental autoimmune encephalomyelitis. Exp. Neurol. 198, 275–284.
Pluchino, S., Quattrini, A., Brambilla, E., Gritti, A., Salani, G., Dina, G., Galli, R., Del Carro, U., Amadio, S., Bergami, A., Furlan, R., Comi, G., Vescovi, A. L., and Martino, G. (2003) Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature 422, 688–694.
Pluchino, S., Zanotti, L., Rossi, B., Brambilla, E., Ottoboni, L., Salani, G., Martinello, M., Cattalini, A., Bergami, A., Furlan, R., Comi, G., Constantin, G., and Martino, G. (2005) Neurosphere-derived multipotent precursors promote neuroprotection by an immunomo dulatory mechanism. Nature 436, 266–271.
Remy, S., Canova, C., Daguin-Nerriere, V., Martin, C., Melchior, B., Neveu, I., Charreau, B., Soulillou, J. P., and Brachet, P. (2001) Different mechanisms mediate the rejection of porcine neurons and endothelial cells transplanted into the rat brain. Xenotransplantation 8, 136–148.
Michel, D. C., Nerriere-Daguin, V., Josien, R., Brachet, P., Naveilhan, P., and Neveu, I. (2006) Dendritic cell recruitment following xenografting of pig fetal mesencephalic cells into the rat brain. Exp. Neurol. 202, 76–84.
Sergent-Tanguy, S., Veziers, J., Bonnamain, V., Boudin, H., Neveu, I., and Naveilhan, P. (2006) Cell surface antigens on rat neural progenitors and characterization of the CD3 (+)/CD3 (−) cell populations. Differentiation 74, 530–541.
Dugast, A. S., Haudebourg, T., Coulon, F., Heslan, M., Haspot, F., Poirier, N., Vuillefroy de Silly, R., Usal, C., Smit, H., Martinet, B., Thebault, P., Renaudin, K., and Vanhove, B. (2008) Myeloid-derived suppressor cells accumulate in kidney allograft tolerance and specifically suppress effector T cell expansion. J. Immunol. 180, 7898–7906.
Acknowledgements
The authors are very grateful to Dr. I. Anegon and Dr. Vanhove for their helpful advices. We also gratefully acknowledge Dr. P. Brachet and Pr. J.-P. Soulillou for their support and encouragement. We also express special thanks to “Etablissement Français du Sang” (EFS, Nantes) that kindly irradiated the NSPCs. The Nestin monoclonal antibody was developed by Susan Hockfield and obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by the University of Iowa, Department of Biological Sciences, Iowa City, IA 52242. The work was supported by the “Association Française contre les Myopathies” (AFM), the “Fédération des Groupements de Parkinsoniens”, and Progreffe. V.Bonnamain was supported by a fellowship from Ministère de l’Enseignement Supérieur et de la Recherche.
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Bonnamain, V., Neveu, I., Naveilhan, P. (2010). In Vitro Analyses of the Immunosuppressive Properties of Neural Stem/Progenitor Cells Using Anti-CD3/CD28-Activated T Cells. In: Cuturi, M., Anegon, I. (eds) Suppression and Regulation of Immune Responses. Methods in Molecular Biology, vol 677. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-869-0_17
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DOI: https://doi.org/10.1007/978-1-60761-869-0_17
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