Differentially promoted peripheral nerve regeneration by grafted Schwann cells over-expressing different FGF-2 isoforms

被引:105
作者
Haastert, K
Lipokatic, E
Fischer, M
Timmer, M
Grothe, C
机构
[1] Hannover Med Sch, Dept Neuroanat, D-30625 Hannover, Germany
[2] Ctr Syst Neurosci, Hannover, Germany
[3] Hannover Med Sch, Dept Neurophysiol, D-30625 Hannover, Germany
关键词
fibroblast growth factor-2; isoforms; peripheral nerve regeneration; cell therapy; neurotrophic therapy; Schwann cells; genetic modification;
D O I
10.1016/j.nbd.2005.06.020
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:138 / 153
页数:16
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