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

Ribeiro, Diogo ; Goya, Rocio Laguna ; Ravindran, Geeta ; Vuono, Romina ; Parish, Clare L. ; Foldi, Claire ; Piroth, Tobias ; Yang, Shanzheng ; Parmar, Malin LU orcid and Nikkhah, Guido , et al. (2013) In Neurobiology of Disease 49. p.118-127
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... (More)
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. (C) 2012 Elsevier Inc. All rights reserved. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Dopaminergic, Human fetal ventral midbrain
in
Neurobiology of Disease
volume
49
pages
118 - 127
publisher
Elsevier
external identifiers
  • wos:000311594600013
  • scopus:84866511789
  • pmid:22940632
ISSN
0969-9961
DOI
10.1016/j.nbd.2012.08.006
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Restorative Neurology (0131000160), Developmental Neurobiology (013210001)
id
b61f3c99-680c-488d-9505-aad3df2de067 (old id 3401027)
date added to LUP
2016-04-01 10:32:11
date last changed
2022-03-19 21:44:27
@article{b61f3c99-680c-488d-9505-aad3df2de067,
  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. (C) 2012 Elsevier Inc. All rights reserved.}},
  author       = {{Ribeiro, Diogo and Goya, Rocio Laguna and Ravindran, Geeta and Vuono, Romina and Parish, Clare L. and Foldi, Claire and Piroth, Tobias and Yang, Shanzheng and Parmar, Malin and Nikkhah, Guido and Hjerling-Leffler, Jens and Lindvall, Olle and Barker, Roger and Arenas, Ernest}},
  issn         = {{0969-9961}},
  keywords     = {{Dopaminergic; Human fetal ventral midbrain}},
  language     = {{eng}},
  pages        = {{118--127}},
  publisher    = {{Elsevier}},
  series       = {{Neurobiology of Disease}},
  title        = {{Efficient expansion and dopaminergic differentiation of human fetal ventral midbrain neural stem cells by midbrain morphogens}},
  url          = {{http://dx.doi.org/10.1016/j.nbd.2012.08.006}},
  doi          = {{10.1016/j.nbd.2012.08.006}},
  volume       = {{49}},
  year         = {{2013}},
}