title: Gene-activated fat grafts for the repair of spinal cord injury: a pilot study.
abstract: BACKGROUND
  Spinal cord injury (SCI) is a complex disease requiring a concerted multi-target approach. The most appropriate combination of therapeutic gene, cellular vehicle, and space filling scaffold still has to be determined. We present an approach that employs syngeneic adipose tissue serving as a three-dimensional biological implant, source of progenitor cells, and delivery system for therapeutic genes. In this pilot experiment, we evaluated the feasibility and short-term effects using gene-activated autologous fat grafts after SCI.
  
  
  METHODS
  An experimental SCI model was established in syngeneic Fischer 344 rats by a T9-T10 hemimyelonectomy. Fat tissue was harvested from two donor rats. Animals were divided into four groups and treated with either (i) fat grafts activated by an adenoviral vector carrying the human NT-3 cDNA, (ii) or BDNF, (iii) or with untreated fat grafts or (iv) remained untreated. Animals were euthanized either 7 or 21 days after surgery, and spinal cord tissue was investigated by histological and immunohistochemical methods.
  
  
  RESULTS
  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. Neither BDNF-activated nor NT-3-activated fat graft had a detectable limiting effect on the neuronal degeneration. BDNF recruited microglia to perilesional site and attenuated their inflammatory response.
  
  
  CONCLUSIONS
  Gene-activated syngeneic fat tissue serves as a three-dimensional biological material delivering therapeutic molecules to the site of SCI over an extended period of time. The BDNF-fat graft attenuated the inflammatory response. Whether these findings translate into functional recovery will require extended observation times.
authors.affiliation: Department of Trauma and Reconstructive Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Volker M
authors.initials: VM
authors.lastname: Betz
authors.affiliation: Department of Neurosurgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
authors.forename: K Hakan
authors.initials: KH
authors.lastname: Sitoci-Ficici
authors.affiliation: Department of Neurosurgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
authors.forename: Ortrud
authors.initials: O
authors.lastname: Uckermann
authors.affiliation: Department of Neurosurgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Leipnitz
authors.affiliation: Department of Neurosurgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Iltzsche
authors.affiliation: SIRION Biotech GmbH, Martinsried, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Thirion
authors.affiliation: SIRION Biotech GmbH, Martinsried, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Salomon
authors.affiliation: Department of Trauma and Reconstructive Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Zwipp
authors.affiliation: Department of Neurosurgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schackert
authors.affiliation: Department of Orthopedic Surgery, University Hospital Grosshadern, University of Munich, Munich, Germany. oliver.betz@med.uni-muenchen.de.
authors.forename: Oliver B
authors.initials: OB
authors.lastname: Betz
authors.affiliation: Department of Neurosurgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany. Matthias.Kirsch@uniklinikum-dresden.de.|DFG-Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany. Matthias.Kirsch@uniklinikum-dresden.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kirsch
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000637:transplantation*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D015316:Genetic Therapy; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D010865:Pilot Projects; D051381:Rats; D011916:Rats, Inbred F344; D013119:Spinal Cord Injuries / Q000601:surgery / Q000628:therapy*; D014184:Transplantation, Homologous
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors
keywords: Functionalized fat graft; Gene therapy; Neurotrophic factors; Spinal cord injury