Peripheral Nerve Injuries and Transplantation of Olfactory Ensheathing Cells for Axonal Regeneration and Remyelination: Fact or Fiction?
Abstract
:1. Introduction
2. OEC Transplantation into Sciatic Nerve Supports Axonal Regeneration and Remyelination
3. Implantation of OEC-Seeded Scaffolds for Nerve Substance Defect Repair
3.1. OECs for Facial Nerve Repair
3.2. OECs in Dorsal Root Injury
4. Concluding Remarks
Supplementary Materials
ijms-13-12911-s001.pdfAcknowledgements
Abbreviations
CHS | collagen-heparan sulphate |
CNS | central nervous system |
DREZ/DH | dorsal root entry zone/dorsal horn |
ECM | extracellular matrix |
EMG | electromyography |
GFP | green fluorescent protein |
CMAP | compound muscle action potential |
Nav | voltage-gated TTX-sensitive sodium channels |
Nav1.6 | voltage gated sodium channel subtype 1.6 |
NGF | nerve growth factor |
NCV | nerve conduction velocity; nerve growth factor |
OB | olfactory bulb |
OECs | olfactory ensheathing cells |
OM | olfactory mucosa |
PDLLA | poly D, L-lactic acid |
PGA | polymer polyglycolic acid |
PHB | poly-3-hydroxybutyrate |
PLGL | poly [LA-co-(Glc-alt-Lys)] |
PLLA | poly L-lactic acid |
p75NGFR | p75 nerve growth factor receptor |
PNS | peripheral nervous system |
SFI | sciatic functional index |
SpC | spinal cord |
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Nerve lesion model | OEC condition | OEC application | Outcome | Limits | Reference |
---|---|---|---|---|---|
Sciatic nerve crush lesion (rat) | GFP-OECs purified 30,000 cells/μL and 10 μL used | OEC injection proximal and distal to lesion | myelin formation and axonal regeneration high density of Na(v)1.6 newly formed nodes of Ranvier | no functional testing performed | Dombrowski et al., 2006 [16] |
Sciatic nerve transection and silicone entubulation (rat) | OB OECs | OECs injected in silicone tube | improvement of CMAP increased nerve fiber regeneration and thickness of myelination | no limits or side effects reported | Cheng et al., 2003 [17] |
Sciatic nerve transaction (rat) | OB OECs | OEC injection in lesion side | enhancement of axonal regeneration reduction of motoneuron apoptosis | no significant difference in neuronal survival in experimental and control groups | Wang et al., 2005 [18] |
Sciatic nerve transaction (rat) | olfactory mucosa transplantation | olfactory mucosa transplantation | SFI increased | Control group only nontransected animals | Delaviz et al.. 2008 [19] |
Sciatic nerve transaction and microsurgical repair by suture (rat) | GFP-OECs purified/PKH labeled 30,000 cells/μL and 10 μL used | OECs injection proximal and distal to lesion | Axonal regeneration and remyelination newly formed nodes of Ranvier functional improvement | Observation interval limited to 3 weeks | Radtke et al., 2009 [20] |
Sciatic nerve lesion 12–15mm gap and tube implantation (rat) | Purified PKH-labelled OB OECs 120,000 cells/tube | Silicone tubel prefilled with OECs in laminin gel | Enhancement axonal regeneration increased CMAP functional improvement | Regeneration limit at 15 mm Regeneration in 50% of animals | Verdu et al., 1999 [21] |
Sciatic nerve lesion 10 mm PLGA conduit implantation (rat) | CM-Dil labeled OECs in 1 × 10,000 μL and 50 μL used | PLGA filled with OECs OECs in EMC | Nerve fiber regenation motor function recovery NCV and CMAP recovery | No recovery SFI after 12 weeks | Li et al., 2010 [22] |
Sciatic nerve lesion 20 mm and PLGA conduit implantation (rat) | Purified OECs Hoechst-labelled 3 × 100,000 μL and 20 μL used | PLGA filled with OECs OECs in EMC | Enhancement axonal regeneration increased myelinated fibers recovery sensory and motor function | 20% of rats showed autophagia and heel ulcers | You et al., 2010 [23] |
Sciatic nerve lesion and 20 mm resection, no surgical repair (rat) | Cultured OECs from olfactory bulb GFP-labelled cells, purity was determined by p75NGFR | Cell suspension was laid into transaction site immediately after resection | Muscle strength and morphometric axon counting with complete restoration, increase of neurotrophic factors | OECs did not directly on axonal regrowth, but seem to create favorable microenviroment | Guerout et al., 2011a [24] |
Sciatic nerve lesion 15 mm and biogenic conduit implantation (rat) | Purified neonatal OECs or purified neonatal SCs | Conduits filled with OECs or SCs | Improvement in motor function | Recovery better after SCs compared to OECs with conduit implantation nerve transplant best results | Penna et al., 2012 [25] |
Facial nerve lesion (rats) 5 mm interstump distance silicone tube | OB OECs deplated of fibroblasts 200,000 OECs | Collagen gel containing OECs in silicone tube | Increased motoneurons 10 fold increase in motoneurons increased sproutuing and pathfinding | No functional alterations | Guntinas-Lichius et al., 2001 [26] |
Facial nerve lesion (rat) end-to end anastomosis | OM freshly prepared detection by y-chromsome | OM laid over sutured epineurium | Reduction of collateral branching promatio of functional recovery sustained expression trophic factors | No improvement of accuracy of reinnervation | Guntinas-Lichius et al., 2002 [27] |
Facial nerve lesion (rat) | OB OECs and OM transplantation | OM pieces were applied OEC suspension injected | Moderate nerve regeneration | Only OM yielded in major improvement | Angelov et al., 2005 [28] |
Fiacial nerve lesion (rat) and immediate repair by suture | Mixed OECs and S-type OECs | Bolus of cultured cells was applied to the cut ends before suture | Increased rate of eye closure recovery | Disorganization of the facial nucleus and aberrant nerve branching unchanged | Choi and Raisman, 2005 [29] |
recurrent laryngeal nerve section/anastomosis (rat) | OECs from mucosa (OM-OECs), or olfactory bulb (OB-OECs) or co-transplantation of both | Cells were laid over section/anastomosis site immediately at the time of surgery (6 ×10,000 cells) | Co-transplantation of OM-OECs and OB-OECs supported major functional recovery with reduction of synkinesis | OM-OECs or OB-OECs displayed opposite abilities to improve functional recovery | Guerout et al., 2011b [30] |
Vagus nerve transaction and immediate repair by suture | Cultivated olfactory bulb or cultivated olfactory mucosa of non-cultivated olfact. mucosa | best vocal fold angular movement with cultivated olfactory mucosa in all cell groups less synkinesis | de Corgnol et al., 2011 [31] | ||
Complete vagus nerve lesion and anastomosis in rat | GPF OM and OB OECs 5 × 1,000,000 cells/animal | OB or OM OECs in matrigel per micropipette in anatomosis side | Improvement of reinnervation (EMG) increased myelinated fibers functional improvement | OM OECs improves muscular activity but no increases in number of myelinated fibers | Pavoit et al., 2011 [32] |
Transection of dorsal roots L3-L6 in rats | OECs from olfactory nerve and glomerular layer, immunopurified marked with PKH28 | Impantation into DREZ | promotion of central regeneration and functional reconnection of regenerating sensory afferents, reflex recovery | immunoreactive fibers entering DH with lower density than contalateral side | Navarro et al., 1999 [33] |
Dorsal root rhizotomy at C3-T3 in rats | purified OB-OECs | direct OEC transplantation dorsal horn OEC transplants or into the DREZ | axons regenerated at the rhizotomy site | no regeneration across DREZ no regeneration into dorsal horn | Gomez et al., 2003 [34] |
Doral root entry zone/dorsal horn rhizotomy in rats | purified by p75NGFR OECs identification by β-gal 30,000–200,000 cells | injection of OEC suspension at DREZ/DH | no advantage in promoting ingrowth of afferent fibers in DREZ | no evidence of functional recovery of afferent fibers, minimal ingrowth of afferent fibers in SpC | Riddell et al., 2004 [35] |
Dorsal root transection at L4 in rats | endogenous matrix containing GFP-OECs | direct application to surfaces of rootlet and SpC combined with fibrin glue | regenerated dorsal root axons crossed repaired DREZ | transplanted cells did not enter the spinal cord itself | Li et al., 2004 [36] |
Cervical or lumbar dorsal root lesion in rats | GFP-OECs from lamina propria | OECs transplanted into DRG, intact or injured dorsal roots or the dorsal columns via DREZ | OECs migration into the DRG/dorsal root | OECs migrated within the PNS but did not cross the DREZ no primary afferent regeneration | Ramer et al., 2004 [37] |
Dorsal roots transection C5-T2 acute and chronic lesion (rats) | GFP-OECs from OB | OECs injection in roots C4-T1 | restoration fore-paw function recovery sensory input axonal regeneration | none of chronically rhizotomized rats showed electrophysiological responses | Ibrahim et al., 2009 [38] |
Dorsal root injury at C7 and C8 in rats | GFP-cultures enriched for OECs 6 × 10,000 cells | stereotactic injection into dorsal horn | attenuation of neuropathic pain | no improvement sensory function increasement of selfmutilation no functional improvement | Wu et al., 2010 [39] |
Avulsion of ventral root at S1 and reimplantation (rat) | GFP-OECs and fibroblasts 1:1 | OECs transplanted at SpC interface OECs matrix cut into pieces | increase of fibers crossing lesion side migration of OECs | 20% of fibers enter roots without OEC transplantation | Li et al., 2007 [17] |
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Radtke, C.; Kocsis, J.D. Peripheral Nerve Injuries and Transplantation of Olfactory Ensheathing Cells for Axonal Regeneration and Remyelination: Fact or Fiction? Int. J. Mol. Sci. 2012, 13, 12911-12924. https://doi.org/10.3390/ijms131012911
Radtke C, Kocsis JD. Peripheral Nerve Injuries and Transplantation of Olfactory Ensheathing Cells for Axonal Regeneration and Remyelination: Fact or Fiction? International Journal of Molecular Sciences. 2012; 13(10):12911-12924. https://doi.org/10.3390/ijms131012911
Chicago/Turabian StyleRadtke, Christine, and Jeffery D. Kocsis. 2012. "Peripheral Nerve Injuries and Transplantation of Olfactory Ensheathing Cells for Axonal Regeneration and Remyelination: Fact or Fiction?" International Journal of Molecular Sciences 13, no. 10: 12911-12924. https://doi.org/10.3390/ijms131012911
APA StyleRadtke, C., & Kocsis, J. D. (2012). Peripheral Nerve Injuries and Transplantation of Olfactory Ensheathing Cells for Axonal Regeneration and Remyelination: Fact or Fiction? International Journal of Molecular Sciences, 13(10), 12911-12924. https://doi.org/10.3390/ijms131012911