Differentially promoted peripheral nerve regeneration by grafted Schwann cells over-expressing different FGF-2 isoforms.
Artificial nerve grafts are needed to reconstruct massive defects in the peripheral nervous system when autologous nerve grafts are not available in sufficient amounts. Nerve grafts containing Schwann cells display a suitable substrate for long-distance regeneration. We present here a comprehensive analysis of the in vivo effects of different isoforms of fibroblast growth factor-2 (FGF-2) on peripheral nerve regeneration across long gaps. FGF-2 isoforms were provided by grafted, genetically modified Schwann cells over-expressing 18-kDa-FGF-2 and 21-/23-kDa-FGF-2, respectively. Functional tests evaluated motor and sensory recovery. Additionally, morphometrical analyses of regenerated nerves were performed 3 and 6 months after grafting. Distinct regeneration promoting effects of the different FGF-2 isoforms were found. 18-kDa-FGF-2 mediated inhibitory effects on the grade of myelination of regenerating axons, whereas 21-/23-kDa-FGF-2 mediated early recovery of sensory functions and stimulation of long-distance myelination of regenerating axons. The results contribute to the development of new therapeutic strategies in peripheral nerve repair.
Haastert
Kirsten
K
Department of Neuroanatomy, Hannover Medical School, OE 4140, Carl-Neuberg-Str.1, 30625 Hannover, Germany. Haastert.kirsten@mh-hannover.de
Lipokatic
Esther
E
Fischer
Martin
M
Timmer
Marco
M
Grothe
Claudia
C
D000818:Animals; D004594:Electrophysiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D007536:Isomerism; D008854:Microscopy, Electron; D009043:Motor Activity; D009046:Motor Neurons / Q000502:physiology / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000502:physiology / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012018:Reflex; D012583:Schwann Cells / Q000502:physiology / Q000637:transplantation*; D012584:Sciatic Nerve / Q000166:cytology / Q000293:injuries* / Q000502:physiology; D014162:Transfection
D016222:Fibroblast Growth Factor 2