A new approach to CNS repair using chimeric peripheral nerve grafts

被引:39
作者
Cui, Q
Pollett, MA
Symons, NA
Plant, GW
Harvey, AR
机构
[1] Univ Western Australia, Sch Anat & Human Biol, Perth, WA 6009, Australia
[2] Univ Western Australia, Reds Spinal Cord Res Lab, CTEC, Perth, WA 6009, Australia
[3] Univ Western Australia, Western Australian Inst Med Res, Perth, WA 6009, Australia
关键词
axon regeneration; axotomy; olfactory ensheathing glia; optic nerve; retinal ganglion cells; Schwann cells; transplantation;
D O I
10.1089/08977150360517155
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
We have examined whether transplanted freeze-thawed peripheral nerve (PN) sheaths repopulated ex vivo with purified adult Schwann cells (SCs) support the regeneration of adult rat retinal ganglion cell (RGC) axons. Cultured adult SCs were derived from donor rats or from the host animals themselves. We also transplanted PN sheaths filled with neonatal SCs or donor adult olfactory ensheathing glia (OEG). 100,000 cells were injected into 1.5-cm lengths of freeze-thawed PN. After 2 days in culture, repopulated PN segments were grafted onto the transected optic nerve of adult Fischer rats. Three weeks later, 6% fluorogold (FG) was applied to distal PN. Retrogradely labeled RGCs were counted in retinal wholemounts and PN grafts were processed for inummohistochemistry. As expected, there was no RGC axon regeneration in cell-free grafts. Regrowth was also absent in neonatal SC- and adult OEG-filled grafts, which contained only small numbers of surviving donor cells. Many cells were, however, seen in adult SC repopulated PN grafts, intermingled with pan-neurofilament(+) and GAP-43(+) fibers. SCs were aligned along the grafts and were S-100(+), p75(+). Ultrastructurally, SCs were associated with myelinated and unmyelinated axons. Hundreds of FG-labeled RGCs were seen in retinas of rats with congeneic or allogeneic PN sheaths repopulated with either donor or autologous (host-derived) adult SCs. Intraocular CNTF injections significantly increased the number of regenerating RGCs in donor and autologous adult SC groups. The use of chimeric grafts to bridge CNS tissue defects could provide a clinical alternative to using multiple PN autografts, the harvesting of which would exacerbate peripheral dysfunction in already injured patients.
引用
收藏
页码:17 / 31
页数:15
相关论文
共 78 条
[1]  
Adlkofer K, 2000, GLIA, V29, P104, DOI 10.1002/(SICI)1098-1136(20000115)29:2<104::AID-GLIA2>3.0.CO
[2]  
2-2
[3]   Peripheral nerve allografting: Review of the literature with relevance to composite tissue transplantation [J].
Bain, JR .
TRANSPLANTATION PROCEEDINGS, 1998, 30 (06) :2762-2767
[4]   The use of adenoviral vectors and ex vivo transduced neurotransplants: Towards promotion of neuroregeneration [J].
Blits, B ;
Dijkhuizen, PA ;
Hermens, WTJMC ;
Van Esseveldt, LE ;
Boer, GJ ;
Verhaagen, J .
CELL TRANSPLANTATION, 2000, 9 (02) :169-178
[5]   Adenoviral vector-mediated expression of a foreign gene in peripheral nerve tissue bridges implanted in the injured peripheral and central nervous system [J].
Blits, B ;
Dijkhuizen, PA ;
Carlstedt, TP ;
Poldervaart, H ;
Schiemanck, S ;
Boer, GJ ;
Verhaagen, J .
EXPERIMENTAL NEUROLOGY, 1999, 160 (01) :256-267
[6]  
BRAY GM, 1987, J EXP BIOL, V132, P5
[7]   Regeneration in the spinal cord [J].
Bregman, BS .
CURRENT OPINION IN NEUROBIOLOGY, 1998, 8 (06) :800-807
[8]  
BUNGE MB, 1999, DEGENERATION REGENER, P171
[9]   IDENTIFICATION OF A LIPID-ANCHORED HEPARAN-SULFATE PROTEOGLYCAN IN SCHWANN-CELLS [J].
CAREY, DJ ;
STAHL, RC .
JOURNAL OF CELL BIOLOGY, 1990, 111 (05) :2053-2062
[10]   Spinal cord repair in adult paraplegic rats: Partial restoration of hind limb function [J].
Cheng, H ;
Cao, YH ;
Olson, L .
SCIENCE, 1996, 273 (5274) :510-513