A combination of NT-4/5 and GDNF is favorable for cultured human nigral neural progenitor cells

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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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > NeuroCenter
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurosurgery
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Veterinary Pharmacology and Toxicology
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Neurochirurgie

UniBE Contributor:

Di Santo, Stefano; Ducray, Angélique; Andereggen, Lukas and Widmer, Hans Rudolf

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 630 Agriculture

ISSN:

1555-3892

Publisher:

Cognizant Communication Corporation

Language:

English

Submitter:

Angélique Ducray

Date Deposited:

04 May 2018 10:43

Last Modified:

11 Jul 2018 01:31

Publisher DOI:

10.1177/0963689717753188

PubMed ID:

29701077

BORIS DOI:

10.7892/boris.114667

URI:

https://boris.unibe.ch/id/eprint/114667

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