Article
L1 over-expressing mouse embryonic stem cells xenografted in a rat model of Parkinson’s disease
L1-überexprimierende embryonale Stammzellen der Maus xenotransplantiert in ein Tiermodell der Parkinson'schen Erkrankung
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Authors
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D. Löttrich
- Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Neurozentrum, Universitätsklinikum Freiburg
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A. Papazoglou
- Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Neurozentrum, Universitätsklinikum Freiburg
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A. Klein
- Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Neurozentrum, Universitätsklinikum Freiburg
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C. Bernreuther
- Zentrum für Molekulare Neurobiologie, Institut für Biosynthese Neuraler Strukturen, Universität Hamburg
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M. Schachner
- Zentrum für Molekulare Neurobiologie, Institut für Biosynthese Neuraler Strukturen, Universität Hamburg
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G. Nikkhah
- Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Neurozentrum, Universitätsklinikum Freiburg
| Published: | May 4, 2005 |
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Outline
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Objective
The cell adhesion molecule L1 shows effects on dopaminergic differentiation and dopaminergic cell survival in vitro. To examine the potential of L1 in vivo, L1 expressing mouse embryonic stem cells were transplanted into the striatum of hemiparkinsonian rats. In this study, we focused on the effect of L1 influence on functional integration, cell survival and differentiation of ES cells in vivo.
Methods
Cells were taken from the inner mass of green fluorescent (GFP) mouse blastocytes and transfected with the L1 gene. The L1 expressing/GFP mouse embryonic stem cells were proliferated in DMEM/F12, L-Glutamine, B27-Supplement, Penicilline/Streptomycine and FGF2 and pre-differentiated for three days under withdrawal of the growth factor. A total number of fifty animals received a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle (MFB). Seventeen animals were transplanted with the L1/GFP expressing mouse embryonic stem cells and another seventeen were grafted with the GFP+ wild type cells without the L1 construct. Both groups received a total cell number of 400,000 cells. A third group of sixteen animals were only grafted with cell culture medium as shams and a fourth group of eight animals were used as healthy controls. Lesion and transplantation effects were validated by apomorphine and amphetamine-nduced rotations and paw-reaching test before and after transplantation.
Results
No change in the apomorphine and amphetamine induced rotations as well as the paw reaching test was observed among the four groups. The morphological analysis revealed teratoma-like tumor formations in a high percentage among the graft recipients (50-60%). Within these tumors, tyrosin hydroxylase (TH) positive neurons were detected in the range from dozens up to several hundreds per graft. Interestingly, the number of TH+ cells in the wild type group was higher and no tumor formation was observed.
Conclusions
In conclusion, there is a clear coherence between mouse embryonic stem cells and tumor formation in a xenograft model. The cell adhesion molecule L1 seems to act differently in vivo than in vitro. TH expression, at least in our model, was impaired and concomitantly tumor formation was enhanced.
