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Title: Enhanced proliferation and dopaminergic differentiation of ventral mesencephalic precursor cells by synergistic effect of FGF2 and reduced oxygen tension

Effective numerical expansion of dopaminergic precursors might overcome the limited availability of transplantable cells in replacement strategies for Parkinson's disease. Here we investigated the effect of fibroblast growth factor-2 (FGF2) and FGF8 on expansion and dopaminergic differentiation of rat embryonic ventral mesencephalic neuroblasts cultured at high (20%) and low (3%) oxygen tension. More cells incorporated bromodeoxyuridine in cultures expanded at low as compared to high oxygen tension, and after 6 days of differentiation there were significantly more neuronal cells in low than in high oxygen cultures. Low oxygen during FGF2-mediated expansion resulted also in a significant increase in tyrosine hydroxylase-immunoreactive (TH-ir) dopaminergic neurons as compared to high oxygen tension, but no corresponding effect was observed for dopamine release into the culture medium. However, switching FGF2-expanded cultures from low to high oxygen tension during the last two days of differentiation significantly enhanced dopamine release and intracellular dopamine levels as compared to all other treatment groups. In addition, the short-term exposure to high oxygen enhanced in situ assessed TH enzyme activity, which may explain the elevated dopamine levels. Our findings demonstrate that modulation of oxygen tension is a recognizable factor for in vitro expansion and dopaminergic differentiation of rat embryonic midbrain precursormore » cells.« less
Authors:
 [1] ;  [2] ; ;  [1] ;  [3] ;  [1]
  1. Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Winslowparken 21, DK-5000 Odense C (Denmark)
  2. (Switzerland)
  3. Department of Neurosurgery, University of Bern, CH-3010 Bern (Switzerland)
Publication Date:
OSTI Identifier:
22212158
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 317; Journal Issue: 12; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BUDR; CATTLE; CULTURE MEDIA; DEOXYURIDINE; DOPA; DOPAMINE; ENZYME ACTIVITY; FIBROBLASTS; GROWTH FACTORS; HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY; HYDROXYLASES; NERVOUS SYSTEM DISEASES; OXYGEN; PEROXIDASES; RATS; SCANNING ELECTRON MICROSCOPY; STEM CELLS; TETRAZOLIUM; TYROSINE