Article
Xenotransplantation of L1 over expressing mouse embryonic stem cells in a rat model of Parkinson’s disease
Xenotransplantation L1 überexprimierender embryonaler Maus-Stammzellen im Tiermodell der Parkinsonschen Krankheit
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Authors
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David Löttrich
- Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Universitätsklinikum Freiburg, Freiburg
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C. Bernreuther
- Zentrum für Molekulare Neurobiologie, Institut für Biosynthese Neuraler Strukturen, Universität Hamburg, Hamburg
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A. Papazoglou
- Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Universitätsklinikum Freiburg, Freiburg
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M. Schachner
- Zentrum für Molekulare Neurobiologie, Institut für Biosynthese Neuraler Strukturen, Universität Hamburg, Hamburg
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G. Nikkhah
- Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Universitätsklinikum Freiburg, Freiburg
| Published: | April 23, 2004 |
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Outline
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Objective
This study was designed to examine the effects of the cell adhesion molecule L1 on the dopaminergic differentiation of transplanted mouse embryonic stem cells. We focused on functional integration, cell survival and differentiation in vivo.
Methods
L1 over expressing and GFP-labelled mouse embryonic stem cells were proliferated in DMEM/F12, L-Glutamine, B27-Supplement, Penicilline/Streptomycine and FGF2 for one and three weeks and differentiated for three days in medium without FGF2. We transplanted a total of twenty-three female Sprague Dawley rats in three groups (two experimental and one control) which were previously unilaterally 6-OHDA lesioned. Each animal received a total cell number of 200,000 cells. The first experimental group (seven animals) received L1-cells proliferated for seven days and the second experimental group (seven animals) received L1-cells proliferated for three weeks. The control group (nine animals) received GFP labelled cells without the L1 construct. Lesion and transplantation effects were validated by apomorphine and amphetamine rotation tests, which were performed three weeks post lesion and two and three weeks post transplantation.
Results
The results demonstrate differential graft survival, depending on the proliferation time in vitro. Grafts allowed to proliferate for three weeks in vitro prior to transplantation demonstrated robust survival and showed substantial differentiation of dopaminergic neurons, in the range of several hundreds. Additionally, signs of teratoma-like tumor formation was observed in a high percentage of graft recipients (90%). In contrast, grafts derived from cell cultures after 1 week of proliferation exhibited only modest survival and no TH expression. Whereas compensation of rotational asymmetry was observed in the first animal group (> 50%), no behavioral recovery was seen in the latter group.
Conclusions
Taken together a clear correlation between graft survival, tumour growth, and a priori cell culture period was found. Furthermore, L1 graft survival also significantly influenced the extent of TH expression. Therefore, the cell adhesion molecule L1 appears to be a promising candidate, molecule relevant for the survival and differentiation of dopaminergic neurons.
