Lentiviral-mediated transfer of CNTF to Schwann cells within reconstructed peripheral nerve grafts enhances adult retinal ganglion cell survival and axonal regeneration

被引：100

作者：

Hu, Y

Leaver, SG

Plant, GW

Hendriks, WTJ

Niclou, SP

Verhaagen, J

Harvey, AR

Cui, Q

机构：

[1] Univ Western Australia, Sch Anat & Human Biol, Med Res Ctr, Western Australian Inst Med Res, Perth, WA 6009, Australia

[2] Univ Western Australia, Sch Anat & Human Biol, Reds Spinal Cord Res Lab, Perth, WA 6009, Australia

[3] Netherlands Inst Brain Res, NL-1105 AZ Amsterdam, Netherlands

[4] Shantou Univ, Coll Med, Lab Neural Repair, Shantou 515031, Peoples R China

来源：

MOLECULAR THERAPY | 2005年 / 11卷 / 06期

基金：

英国医学研究理事会;

关键词：

axonal regeneration; retinal ganglion cells; lentiviral vectors; ciliary neurotrophic factor; Schwann cells; tissue engineering; gene therapy;

D O I：

10.1016/j.ymthe.2005.01.016

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

We recently described a method for reconstituting peripheral nerve (PN) sheaths using adult Schwann cells (SCs). Reconstructed PN tissue grafted onto the cut optic nerve supports the regeneration of injured adult rat retinal ganglion cell (RGC) axons. To determine whether genetic manipulation of such grafts can further enhance regeneration, adult SCs were transduced with lentiviral vectors encoding either ciliary neurotrophic factor (LV-CNTF) or green fluorescent protein (LV-GFP). SCs expressed transgenes for at least 4 weeks after transplantation. There were high levels of CNTF mRNA and CNTF protein in PN grafts containing LV-CNTF-transduced SCs. Mean RGC survival was significantly increased with these grafts (11,863/retina) compared with LV-GFP controls (7064/retina). LV-CNTF-transduced SCs enhanced axonal regeneration to an even greater extent (3097 vs 393 RGCs/retina in LV-GFP controls). Many regenerated axons were myelinated. The use of genetically modified, reconstituted PN grafts to bridge tissue defects may provide new therapeutic strategies for the treatment of both CNS and PNS injuries.

引用

页码：906 / 915

页数：10

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