Journal article
Efficient expansion and dopaminergic differentiation of human fetal ventral midbrain neural stem cells by midbrain morphogens
D Ribeiro, R Laguna Goya, G Ravindran, R Vuono, CL Parish, C Foldi, T Piroth, S Yang, M Parmar, G Nikkhah, J Hjerling-Leffler, O Lindvall, RA Barker, E Arenas
Neurobiology of Disease | Published : 2013
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, Wnt5..
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Awarded by Seventh Framework Programme
Funding Acknowledgements
We would like to thank all members of the Arenas group for fruitful discussions, to Johny Soderlund and Pam Tyers for technical support and Alessandra Nani for secretarial assistance. This work was supported by grants from the Swedish Research Council (VR2008:2811, VR2008:3287 and DBRM), Karolinska Institutet, Parkinsonfonden, German Parkinson Foundation (dPV), National Health and Medical Research Council Australia (NHMRC) and the European Commission under the 7th Framework Programme - HEALTH - Collaborative Projects: NeuroStemcell (European Consortium for Stem Cell Therapy in Neurodegenerative Diseases) and Transeuro (Contract no. 242003). DR was supported by the Foundation for Science and Technology from the Portuguese Government (SFRH/BD/24585/2005). CLP was supported by a National Health and Medical Research Council, Australia (NHMRC) CJ Martin training fellowship, an NHMRC career development award and a Viertel senior medical research fellowship, Australia.