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

In English

Författare

  • Diogo Ribeiro
  • Rocio Laguna Goya
  • Geeta Ravindran
  • Romina Vuono
  • Clare L. Parish
  • Claire Foldi
  • Tobias Piroth
  • Shanzheng Yang
  • Malin Parmar
  • Guido Nikkhah
  • Jens Hjerling-Leffler
  • Olle Lindvall
  • Roger Barker
  • Ernest Arenas
Visa allt

Summary, in English

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.

Publiceringsår

2013

Språk

Engelska

Sidor

118-127

Publikation/Tidskrift/Serie

Neurobiology of Disease

Volym

49

Dokumenttyp

Artikel i tidskrift

Förlag

Elsevier

Ämne

  • Neurosciences

Nyckelord

  • Dopaminergic
  • Human fetal ventral midbrain

Status

Published

Forskningsgrupp

  • Developmental and Regenerative Neurobiology

ISBN/ISSN/Övrigt

  • ISSN: 0969-9961