Artikel
Combined therapeutic strategies for functional recovery of peripheral nerves after substance loss: Transplantation of ex vivo genetically modified Schwann cells and post-reconstruction exercise
Kombinierte therapeutische Konzepte für die funktionelle Wiederherstellung peripherer Nerven nach Substanzverlust: Transplantation von ex-vivo genetisch veränderten Schwann-Zellen und post-operatives Training
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Autoren
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K. Haastert
- Abteilung für Neuroanatomie, Medizinische Hochschule Hannover und Zentrum für Systemische Neurowissenschaften (ZSN) Hannover
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C. Mauritz
- Abteilung für Neuroanatomie, Medizinische Hochschule Hannover und Zentrum für Systemische Neurowissenschaften (ZSN) Hannover
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E. Lipokatic
- Abteilung für Neuroanatomie, Medizinische Hochschule Hannover und Zentrum für Systemische Neurowissenschaften (ZSN) Hannover
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C. Matthies
- Neurochirurgische Klinik und Poliklinik, Kopfklinikum, Universitätsklinikum Würzburg
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Z. Ying
- Department of Physiological Science, University of California Los Angeles; USA
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F. Gomez-Pinilla
- Department of Physiological Science, University of California Los Angeles; USA
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C. Grothe
- Abteilung für Neuroanatomie, Medizinische Hochschule Hannover und Zentrum für Systemische Neurowissenschaften (ZSN) Hannover
| Veröffentlicht: | 11. April 2007 |
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Gliederung
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Objective: Functional peripheral nerve regeneration (PNR) across long gaps is still not guaranteed even with modern neurosurgical techniques. Genetically modified Schwann cells (SC) over-expressing regeneration promoting proteins are promising tools in a clinical context of cell transplantation for PNR. Furthermore, voluntary wheel running increases axonal regeneration after crush injury in rats.
Methods: Morphometrical, molecular and functional aspects of PNR were investigated after transection and tissue engineered reconstruction of adult rat sciatic nerves. Gap-bridging tubular grafts were either filled with Matrigel alone or genetically different neonatal rat SC in Matrigel. Transplanted SC over-expressing fibroblast growth factor-2 (FGF-2) were compared with physiological SC. Post-transplantational voluntary running exercise was investigated as additional stimulus for motor recovery, examined by sciatic function index (SFI) analysis.
Results: Transplantation of SC over-expressing FGF-2 resulted in significantly longer and more regenerated myelinated axons (MA) compared to other transplantation conditions. In addition, somatic gene transfer of FGF-2 facilitated sensory recovery [1].
However, short-term exercise (7 days) after SC transplantation did significantly improve motor performance. In correlation to this functional finding, significantly elevated mRNA levels of GAP (Growth Associated Protein)-43 and Synapsin I were found in the lumbar spinal cord of SC transplanted, exercising rats. Long-term exercise (≤4 weeks) after transplantation demonstrated significantly enhanced motor performance of exercising animals. Although, time pattern and grade of motor recovery differed between the groups. Nevertheless, morphometrical tissue analysis revealed significant more regenerated MA after transplantation of FGF-2 over-expressing SC into exercising animals as compared to sedentary rats.
Conclusions: Somatic gene transfer of FGF-2 seemed to specifically promote sensory nerve recovery, whereas motor recovery could not be achieved1.
Our results regarding voluntary exercise during the rehabilitation phase after tissue engineered peripheral nerve reconstruction suggest so far that exercise enhances SC transplant-promoted axonal regeneration and promotes establishment of functional connections.
To follow our aim of clinical use of genetically modified autologous SC transplants, we already established genetic modification of highly enriched adult human SC, suitable for cell transplantation approaches [2].
