Pharmacologically active microcarriers releasing glial cell line -: derived neurotrophic factor:: Survival and differentiation of embryonic dopaminergic neurons after grafting in hemiparkinsonian rats

To improve the outcome of foetal dopaminergic cell transplantation for the treatment of Parkinson's disease, pharmacologically active microcarriers (PAM) were developed. PAM are able to convey cells on their surface and release a growth factor to improve cell survival, differentiation and integration after brain implantation. Lysozyme-releasing PAM were first produced and characterized. They served as a model system for the development of glial cell line-derived neurotrophic factor (GDNF)-releasing PAM conveying foetal ventral mesencephalic (FVM) cells. The effects of the intrastriatal implantation of this system were studied in hemiparkinsonian rats during a 6-week period. This study reports on the degradation of coated and non-coated PAM and the release of lysozyme and of biologically active GDNF for 42 days. Unloaded and GDNF-loaded PAM conveying FVM cells allowed a high improvement of the grafted cell survival and of fibre outgrowth, when compared to the cells transplanted alone. The animals receiving the PAM showed an earlier improvement in amphetamine-induced rotational behaviour compared to animals receiving FVM cells only; behaviour that appears to be more regular and stable with the GDNF-releasing PAM. The use of PAM to convey foetal cells is thus an efficient strategy for cell therapy in neurodegenerative diseases, as it allows improvement of cell survival and fibre outgrowth inducing a rapid recovery of behaviour using only low amounts of cells. (c) 2007 Elsevier Ltd. All rights reserved.