PMID- 17689533 OWN - NLM STAT- MEDLINE DCOM- 20080108 LR - 20141120 IS - 0014-4886 (Print) IS - 0014-4886 (Linking) VI - 207 IP - 2 DP - 2007 Oct TI - The importance of transgene and cell type on the regeneration of adult retinal ganglion cell axons within reconstituted bridging grafts. PG - 314-28 AB - When grafted onto the cut optic nerve, chimeric peripheral nerve (PN) sheaths reconstituted with adult Schwann cells (SCs) support the regeneration of adult rat retinal ganglion cell (RGC) axons. Regrowth can be further enhanced by using PN containing SCs transduced ex vivo with lentiviral (LV) vectors encoding a secretable form of ciliary neurotrophic factor (CNTF). To determine whether other neurotrophic factors or different cell types also enhance RGC regrowth in this bridging model, we tested the effectiveness of (1) adult SCs transduced with brain-derived neurotrophic factor (BDNF) or glial cell line-derived neurotrophic factor (GDNF), and (2) fibroblasts (FBs) genetically modified to express CNTF. SCs transduced with LV-BDNF and LV-GDNF secreted measurable and bioactive amounts of each of these proteins, but reconstituted grafts containing LV-BDNF or LV-GDNF transduced SCs did not enhance RGC survival or axonal regrowth. LV-BDNF modified grafts did, however, contain many pan-neurofilament immunolabeled axons, many of which were also immunoreactive for calcitonin gene-related peptide (CGRP) and were presumably of peripheral sensory origin. Nor-adrenergic and cholinergic axons were also seen in these grafts. There were far fewer axons in LV-GDNF engineered grafts. Reconstituted PN sheaths containing FBs that had been modified to express CNTF did not promote RGC viability or regeneration, and PN reconstituted with a mixed population of SCs and CNTF expressing FBs were less effective than SCs alone. These data show that both the type of neurotrophic factor and the cell types that express these factors are crucial elements when designing bridging substrates to promote long-distance regeneration in the injured CNS. FAU - Hu, Ying AU - Hu Y AD - School of Anatomy and Human Biology, The University of Western Australia, Crawley, WA 6009, Australia. FAU - Arulpragasam, Ajanthy AU - Arulpragasam A FAU - Plant, Giles W AU - Plant GW FAU - Hendriks, William T J AU - Hendriks WT FAU - Cui, Qi AU - Cui Q FAU - Harvey, Alan R AU - Harvey AR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070808 PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Ciliary Neurotrophic Factor) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Tubb3 protein, rat) RN - 0 (Tubulin) SB - IM MH - Analysis of Variance MH - Animals MH - Axons/*physiology MH - Brain-Derived Neurotrophic Factor/biosynthesis/therapeutic use MH - Cells, Cultured MH - Ciliary Neurotrophic Factor/metabolism MH - Enzyme-Linked Immunosorbent Assay/methods MH - Female MH - Gene Expression Regulation/drug effects/physiology MH - Glial Cell Line-Derived Neurotrophic Factor/biosynthesis/therapeutic use MH - Lentivirus/physiology MH - Nerve Regeneration/*physiology MH - Optic Nerve Injuries/pathology/physiopathology/*therapy MH - Rats MH - Rats, Inbred F344 MH - Rats, Sprague-Dawley MH - Retinal Ganglion Cells/*pathology MH - Schwann Cells/physiology/transplantation MH - Tissue Engineering/*methods MH - Transduction, Genetic/*methods MH - Tubulin/metabolism EDAT- 2007/08/11 09:00 MHDA- 2008/01/09 09:00 CRDT- 2007/08/11 09:00 PHST- 2007/04/27 00:00 [received] PHST- 2007/06/27 00:00 [revised] PHST- 2007/07/02 00:00 [accepted] PHST- 2007/08/11 09:00 [pubmed] PHST- 2008/01/09 09:00 [medline] PHST- 2007/08/11 09:00 [entrez] AID - S0014-4886(07)00262-2 [pii] AID - 10.1016/j.expneurol.2007.07.001 [doi] PST - ppublish SO - Exp Neurol. 2007 Oct;207(2):314-28. doi: 10.1016/j.expneurol.2007.07.001. Epub 2007 Aug 8.