Di Santo, Stefano; Meyer, M; Ducray, Angélique; Andereggen, Lukas; Widmer, Hans Rudolf (2018). A combination of NT-4/5 and GDNF is favorable for cultured human nigral neural progenitor cells. Cell transplantation, 27(4), pp. 648-653. Cognizant Communication Corporation 10.1177/0963689717753188
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28_ DiSanto et al 2017 GDNF and NT4-5 are favorable for culture human nigral neural progenitor cells.pdf - Accepted Version Available under License Creative Commons: Attribution-Noncommercial (CC-BY-NC). Download (1MB) | Preview |
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0963689717753188.pdf - Published Version Available under License Creative Commons: Attribution-Noncommercial (CC-BY-NC). Download (325kB) | Preview |
Idiopathic Parkinson’s disease is a progressive neurodegenerative disorder
clinically manifested by cardinal motor symptoms including tremor at rest,
bradykinesia and muscle rigidity. Transplantation of dopaminergic neurons
is an experimental therapy for Parkinson’s disease, however, limited by
suboptimal integration and low survival of grafts. Pretreatment of donor
tissue may offer a strategy to improve properties of transplanted
dopaminergic neurons and thereby clinical outcome. We have previously
shown that a combination of neurotrophin-4/5 (NT-4/5) and glial cell linederived
neurotrophic factor (GDNF) demonstrated additive effects on rat
ventral mesencephalic tissue. The present study investigated the effects of
NT-4/5 and GDNF as single factors or in combination on dopaminergic
neurons in organotypic explant cultures of fetal human ventral
mesencephalon. For that purpose free-floating roller-tube cultures were
prepared from ventral mesencephali and the equally sized pieces grown for
one week in presence or absence of neurotrophic factors. Both
neurotrophic factors increased dopamine content in the culture medium
and number of tyrosine hydroxylase immunoreactive (ir) neurons, most
prominently after combined GDNF+NT-4/5 treatment. Culture volumes did not differ between groups, while content of lactate dehydrogenase in the
culture medium was moderately reduced in all treated groups. In
conclusion, we identified that a combination of GDNF and NT-4/5 robustly
promoted differentiation and survival of human fetal ventral mesencephalic
dopaminergic neurons, an observation with potential promising impact for
cell replacement approaches in Parkinson's disease.
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