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Efficient expansion and dopaminergic differentiation of human fetal ventral midbrain neural stem cells by midbrain morphogens

Ribeiro, D., Laguna Goya, R., Ravindran, G., Vuono, Romina, Parish, C.L., Foldi, C., Piroth, T., Yang, S., Parmar, M., Nikkhah, G., and others. (2013) Efficient expansion and dopaminergic differentiation of human fetal ventral midbrain neural stem cells by midbrain morphogens. Neurobiology of Disease, 49 (1). pp. 118-127. ISSN 0969-9961. (doi:10.1016/j.nbd.2012.08.006) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:79838)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL:
https://doi.org/10.1016/j.nbd.2012.08.006

Abstract

Human fetal midbrain tissue grafting has provided proof-of-concept for dopamine cell replacement therapy (CRT) in Parkinson's disease (PD). However, limited tissue availability has hindered the development and widespread use of this experimental therapy. Here we present a method for generating large numbers of midbrain dopaminergic (DA) neurons based on expanding and differentiating neural stem/progenitor cells present in the human ventral midbrain (hVM) tissue. Our results show that hVM neurospheres (hVMN) with low cell numbers, unlike their rodent counterparts, expand the total number of cells 3-fold, whilst retaining their capacity to differentiate into midbrain DA neurons. Moreover, Wnt5a promoted DA differentiation of expanded cells resulting in improved morphological maturation, midbrain DA marker expression, DA release and electrophysiological properties. This method results in cell preparations that, after expansion and differentiation, can contain 6-fold more midbrain DA neurons than the starting VM preparation. Thus, our results provide evidence that by improving expansion and differentiation of progenitors present in the hVM it is possible to greatly enrich cell preparations for DA neurons. This method could substantially reduce the amount of human fetal midbrain tissue necessary for CRT in patients with PD, which could have major implications for the widespread adoption of this approach.

Item Type: Article
DOI/Identification number: 10.1016/j.nbd.2012.08.006
Uncontrolled keywords: dopamine; Wnt5a protein; dopamine; oncoprotein; Wnt protein; WNT5A protein, human, article; cell count; cell expansion; cell maturation; cell structure; controlled study; dopamine release; dopaminergic system; fetus; human; human tissue; mesencephalon; nerve cell culture; nerve cell differentiation; nervous system electrophysiology; neural stem cell; priority journal; protein expression; culture technique; cytology; dopaminergic nerve cell; embryology; high performance liquid chromatography; immunohistochemistry; metabolism; nervous system development; neural stem cell; patch clamp technique; physiology; polymerase chain reaction, Cell Count; Cell Culture Techniques; Chromatography, High Pressure Liquid; Dopamine; Dopaminergic Neurons; Humans; Immunohistochemistry; Mesencephalon; Neural Stem Cells; Neurogenesis; Patch-Clamp Techniques; Polymerase Chain Reaction; Proto-Oncogene Proteins; Wnt Proteins
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Romina Vuono
Date Deposited: 29 Jan 2020 10:55 UTC
Last Modified: 16 Feb 2021 14:11 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/79838 (The current URI for this page, for reference purposes)

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