Artikel
Functional integration of mesenchymal adult stem cells in the rodent brain
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Autoren
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G. Lepski
- Klinik für Neurochirurgie, Eberhard-Karls-Universität Tübingen
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C. Jannes
- Klinik für Neurochirurgie, Eberhard-Karls-Universität Tübingen
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M. Tatagiba
- Klinik für Neurochirurgie, Eberhard-Karls-Universität Tübingen
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G. Nikkhah
- Klinik für Neurochirurgie, Albert-Ludwig-Universität Freiburg
| Veröffentlicht: | 20. Mai 2009 |
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Gliederung
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Objective: Many neurological diseases impose severe deficits on patients, and there is no effective treatment available for these diseases. The possibility of neurorrestoration has brought new hope to this field, and the successful integration and differentiation of stem cells in the adult brain has become an important goal. In this work we tried to find out whether adult mesenchymal stem cells from rats have the ability to differentiate into mature neurons and to generate new circuits in the host adult brain.
Methods: Mesenchymal stem cells were isolated from the bone marrow of adult Sprague-Dowley rats and transfected with lentivirus for expression of green fluorescent protein (GFP). The isolated cells were cultivated in a medium containing increased cAMP for the induction of neuronal phenotypes. A cell suspension was implanted stereotactically into the hippocampus of 30 young Sprague-Dowley rats, at 150,000 cells per deposit. Three months after surgery, the animals were sacrificed through decapitation and brains immediately removed for fluorescence-guided patch clamp recordings. Immunhistochemistry with MAP2, NeuN, and NF200 was used to confirm neuronal differentiation. Cells co-expressing NeuN and GFP were counted stereologically in the hippocampus.
Results: The isolated cell population was able to differentiate into mature neurons in vitro, and were positively stained for NeuN, MAP2 and NF200. Three months after implantation, mature neurons derived from the donor could be identified by expression of neuronal markers together with GFP. Patch clamp recordings in brain slices revealed normal neuronal electrophysiological activity with spontaneous excitatory and inhibitory post-synaptic potentials on the implanted cells, confirming functional maturation and integration into the local hippocampal circuitry. We counted stereologically 1472±418 double-labeled cells (NeuN-GFP) in the hippocampus.
Conclusions: This is the first report successfully demonstrating the maturation and functional integration of mesenchymal adult stem cells in the host brain, and it represents an important step toward neurorestoration with adult stem cells.
