Potencial of adult neural stem cells for the treatment of Parkinson`s disease.

MATHIEU PATRICIA A., PITOSSI FERNANDO.

Búzios - Brasil

Congreso; I IBRO/LARC Congreso of Neurosciences of Latin America, the Caribbean and Iberian Peninsula.; 2008

Potential of adult neural stem cells for the treatment of Parkinson`s disease Mathieu P. A.1,2 and Pitossi F.1 1 Laboratory for regenerative and protective therapies of the nervous system Fundación Instituto Leloir – CONICET-Ciudad de Buenos Aires 2 FFyB - UBA - Ciudad de Buenos Aires Parkinson´s disease is a neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons of the substancia nigra pars compacta. In the search of new sources of cells for regenerative therapies, the adult neural stem cells (aNSC) are an alternative because these cells are able to differentiate into neurons, astrocytes and oligodendrocytes in vitro and in vivo. Our group observed that the transforming growth factor beta (TGF-beta) is pro-neurogenic on NSC in vivo and in vitro. The objective of our work is to study the use in regenerative and protective therapies of aNSC obtained from one of main areas in the brain where neurons are generated during adulthood, the subventricular layer in the lateral ventricles (SVZ).             We performed primary cultures dissecting the SVZ of 8 to 10 moth old Wistar rats. These cultures were characterized by Nestin, astrocyte marker (GFAP), microglia (GSA) and beta III tubulin (Tuj) immunocytochemistry. Besides, the effect of TGF-beta on aNSC was analyzed by adding the cytokine in the culture medium. Survival and inflammatory response after striatum transplantation of undifferentiated aNSC were determined one, three and six weeks after the grafting. At that time points animals were perfused intracardially, brains were dissected out and Nissl staining and GFAP or GSA immunohistochemistry were performed to analyzed inflammatory response to the transplant and transplanted cells survival. Preliminary results showed that in primary cultures 7.4% of the cells were Tuj, 1.1% GFAP and 2.5% GSA-positive, respectively. TGF-beta improved the percentage of Tuj positive cells by one fold. On the other hand, transplanted aNSC were identifiable 1, 3 and 6 weeks after transplantation. Although a large portion of grafted cells underwent cell death 14.5% were identified after 6 weeks and the inflammation was only evident in the graft area. These data show that aNSC could become an important source for cell based therapies for neurodegenerative disease and TGF-beta might be a promising tool for aNSC neuronal differentiation.