Get started
Work

In-vitro kultivierte Vorläuferzellen des Ventralen Mesencephalons von Rattenembryonen in verschiedenen embryonalen Differenzierungsstadien : eine Untersuchung von Zellen zu Genen

Year: 2007
Type: dissertation
Abstract: Parkinson’s disease (PD) is a well-known neurodegenerative disease characterized by loss of dopaminergic neurons (DNs) in the substantia nigra. Implanting healthy DNs seems to be an ideal restorative therapy. However, the limited availability of DNs becomes a main obstacle. Embryonic ventral mesencephalic precursor cells (VMPCs) have been shown to produce considerable DNs in vitro. In the first experiment, different VMPCs from different rat embryos with crown-rump lengths of 3-4mm, 5-6mm, 7-8mm, 9-10mm and 11-12mm were expanded for 7 days with bFGF, and induced to differentiate in vitro for next 7 days with AA-2P. Immunocytochemical staining revealed that the ratio of TH+ cells in the total cell population derived from 5-6mm embryos was highest. Although there was no significant difference related to the yields of β- III Tubulin+ immature neurons between the 3-4mm embryo culture and the 5-6mm embryo culture, the ratio of TH+ cells versus β-III Tubulin+ cells in the 5-6mm embryo culture was also higher than that in the 3-4mm embryo culture. In order to identify the molecular difference critical to DN maturation, the changes of gene expression profiling in the 3-4mm, 4-5mm and 5-6mm embryo cultures derived from inbred rats were analyzed with Affymetrix microarray on 3 different time points in the second experiment. Totally 114 known genes, together with 344 unknown Expressed Sequence Tags (ESTs), were found to be significantly up- or down-regulated simultaneously in all those 3 cultures. Among them, 36 known gene and 46 ESTs were differently expressed between the 3-4mm embryo culture and the 5-6mm embryo culture on at least one time point. Moreover, among these 36 known genes, 10 were related to matrix formation mainly by fibroblasts, 3 related to active astrocytes and another 3 related to oligodendrocytes. In addition, 7 genes were involved in the regulation of cell growth and differentiation. Another 7 had special molecular functions like calcium ion binding. Further exploration on these known genes and unknown ESTs will find novel factors or mechanisms strongly influencing the maturation process of DNs. These findings may promote the current scientific attempts to develop precursor cell-based neural transplantation approaches for PD.
Language: English
Open Access status: green
OpenAlex ID: W7126303343
Cites:
Cited by:
Related to: 10