Efficient expansion and dopaminergic differentiation of human fetal ventral midbrain neural stem cells by midbrain morphogens
(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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- author
- organization
- publishing date
- 2013
- 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}}, }