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

Jensen, Pia; Gramsbergen, Jan-Bert; Zimmer, Jens; Widmer, Hans R; Meyer, Morten (2011). Enhanced proliferation and dopaminergic differentiation of ventral mesencephalic precursor cells by synergistic effect of FGF2 and reduced oxygen tension. Experimental cell research, 317(12), pp. 1649-62. San Diego, Calif.: Elsevier 10.1016/j.yexcr.2011.04.012

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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 precursor cells.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurosurgery
UniBE Contributor:	Widmer, Hans Rudolf
ISSN:	0014-4827
Publisher:	Elsevier
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:23
Last Modified:	05 Dec 2022 14:06
Publisher DOI:	10.1016/j.yexcr.2011.04.012
PubMed ID:	21570391
Web of Science ID:	000292181600001
URI:	https://boris.unibe.ch/id/eprint/7980 (FactScience: 213378)