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

Autor: Ribeiro D; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, S-171 77 Stockholm, Sweden., Laguna Goya R; Cambridge Centre for Brain Repair, University of Cambridge, Forvie Site, Robinson Way, Cambridge CB2 0PY, UK., Ravindran G; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, S-171 77 Stockholm, Sweden., Vuono R; Cambridge Centre for Brain Repair, University of Cambridge, Forvie Site, Robinson Way, Cambridge CB2 0PY, UK., Parish CL; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, S-171 77 Stockholm, Sweden., Foldi C; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, S-171 77 Stockholm, Sweden., Piroth T; Laboratory of Molecular Neurosurgery and Neurological Clinic, Department of Stereotactical Neurosurgery, University Freiburg Medical Center, Breisacher Str. 64, 79106 Freiburg i. B., Germany., Yang S; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, S-171 77 Stockholm, Sweden., Parmar M; Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, BMC A11, 22184 Lund, Sweden., Nikkhah G; Laboratory of Molecular Neurosurgery and Neurological Clinic, Department of Stereotactical Neurosurgery, University Freiburg Medical Center, Breisacher Str. 64, 79106 Freiburg i. B., Germany., Hjerling-Leffler J; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, S-171 77 Stockholm, Sweden., Lindvall O; Laboratory of Neurogenesis and Cell Therapy, Wallenberg Neuroscience Center and Lund Stem Cell Center, University Hospital, SE-221 84 Lund, Sweden., Barker RA; Cambridge Centre for Brain Repair, University of Cambridge, Forvie Site, Robinson Way, Cambridge CB2 0PY, UK., Arenas E; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, S-171 77 Stockholm, Sweden. Electronic address: ernest.arenas@ki.se.
Jazyk: angličtina
Zdroj: Neurobiology of disease [Neurobiol Dis] 2013 Jan; Vol. 49, pp. 118-27. Date of Electronic Publication: 2012 Aug 24.
DOI: 10.1016/j.nbd.2012.08.006
Abstrakt: 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.
(Copyright © 2012 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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