Artikel
Gene activated fat grafts for the repair of spinal cord injury: a pilot study
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Autoren
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K. Hakan Sitoci-Ficici
- Klinik und Poliklinik für Neurochirurgie, Carl Gustav Carus Universitätsklinikum, Technische Universität Dresden, Dresden, Deutschland
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Volker M. Betz
- Klinik und Poliklinik für Unfall- und Wiederherstellungschirurgie, Carl Gustav Carus Universitätsklinikum, Technische Universität Dresden, Dresden, Deutschland
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Ortrud Uckermann
- Klinik und Poliklinik für Neurochirurgie, Carl Gustav Carus Universitätsklinikum, Technische Universität Dresden, Dresden, Deutschland
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Elke Leipnitz
- Klinik und Poliklinik für Neurochirurgie, Carl Gustav Carus Universitätsklinikum, Technische Universität Dresden, Dresden, Deutschland
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Anne Iltzsche
- Klinik und Poliklinik für Neurochirurgie, Carl Gustav Carus Universitätsklinikum, Technische Universität Dresden, Dresden, Deutschland
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Christian Thirion
- SIRION Biotech GmbH, Martinsried, Deutschland
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Michael Salomon
- SIRION Biotech GmbH, Martinsried, Deutschland
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Hans Zwipp
- Klinik und Poliklinik für Unfall- und Wiederherstellungschirurgie, Carl Gustav Carus Universitätsklinikum, Technische Universität Dresden, Dresden, Deutschland
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Gabriele Schackert
- Klinik und Poliklinik für Neurochirurgie, Carl Gustav Carus Universitätsklinikum, Technische Universität Dresden, Dresden, Deutschland
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Oliver B. Betz
- Klinik und Poliklinik für Orthopädie, Klinikum Großhadern, Ludwig-Maximilians-Universität München, München, Deutschland
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Matthias Kirsch
- Klinik und Poliklinik für Neurochirurgie, Carl Gustav Carus Universitätsklinikum, Technische Universität Dresden, Dresden, Deutschland
| Veröffentlicht: | 21. Mai 2013 |
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Gliederung
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Objective: Gene-based therapies offer great promise for the treatment of spinal cord injury. However, the most appropriate combination of therapeutic gene, cellular vehicle and space filling scaffold still has to be determined. In this pilot experiment, we evaluated the feasibility and short-term effects using autologous gene activated fat grafts for spinal cord repair.
Method: Experimental spinal cord injury was produced in Fischer-344 rats (n=24) by T9-T10 hemimyelonectomy and animals were divided in four groups. Spinal cord defects were treated with either (I) syngeneic fat grafts activated by an adenoviral vector carrying the human NT-3 cDNA (n=4), (II) fat grafts transduced by an adenoviral vector carrying BDNF (n=4), (III) untreated fat grafts (n=8) or (IV) remained untreated (n=8). Half of the animals of each group were euthanized either 7 or 21 days after surgery and spinal cord tissue was investigated by H&E based histology and selective antibody staining for iba-1, GFAP, and β-III-Tubulin.
Results: Neurotrophic factors NT-3 and BDNF were produced by gene activated fat grafts for at least 21 days in vitro and in vivo. Fat tissue grafts remained stable at the site of implantation at 7 days and at 21 days. In the BDNF group, reduced microglia activation and macrophage infiltration after spinal cord injury was detected. Axonal elongation into the adipose tissue did not reach statistical significance in the gene activated fat graft groups within the “short” observation period.
Conclusions: Gene activated autologous fat tissue can serve as a three-dimensional scaffold delivering therapeutic molecules to the site of spinal cord injury over an extended period of time. The fat tissue implant led to a significantly reduced scar development at the injury site. Investigations into improved functional restoration require extended observation times.
