Abstract
Spinal cord injury is characterized by massive cellular and axonal loss, a neurotoxic environment, inhibitory molecules and physical barriers that hamper nerve regeneration and reconnection leading to chronic paralysis. Transplantation of different types of cells is one of the strategies being examined in order to restore the lost cell populations and to re-establish a permissive environment for nerve regeneration. The mammalian olfactory system is one of the few zones in the body where neurogenesis occurs during the lifetime of the organism, with olfactory neurons being replaced daily with their axons elongating from the peripheral nervous system into the central nervous system to re-establish functional connections. The regenerative ability of this system is largely attributed to the presence of a unique group of cells called olfactory ensheathing cells (OECs). OECs have emerged as an encouraging cell candidate for transplantation therapies to repair the injured spinal cord with multiple animal models showing significant functional improvements and several human trials establishing that the procedure is safe and feasible. Even though the results are promising with some animal models showing remarkable restoration of function, the variability amongst studies in terms of outcome assessments, cell purity, cell culture and transplantation protocols make it difficult to reach firm conclusions about the effectiveness of OEC transplant therapy to treat the injured spinal cord. These variations need to be addressed in order to achieve a more realistic understanding of how the benefits of OEC transplantation enhance the therapeutic outcomes.
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Abbreviations
- BDNF:
-
Brain-derived neurotrophic factor
- cAMP:
-
Cyclic adenosine monophosphate
- CNS:
-
Central nervous system
- CP:
-
Cribriform plate
- CSPG:
-
Chondroitin sulfate proteoglycan
- DAPI:
-
4’,6-diamidino-2-phenylindole
- dBcAMP:
-
Dibutyryl cyclic adenosine monophosphate
- FGF:
-
Fibroblast growth factor
- GDNF:
-
Glial cell-derived neurotrophic factor
- GFAP:
-
Glial fibrillary acidic protein
- GL:
-
Glomerular layer
- HNK-1:
-
Human natural killer-1
- IGF:
-
Insulin-like growth factor
- LP:
-
Lamina propria
- MAG:
-
Myelin associated glycoprotein
- NFL:
-
Nerve fibre layer
- NGF:
-
Nerve growth factor
- Nogo:
-
Neurite outgrowth inhibitory protein
- NPY:
-
Neuropeptide Y
- NT4:
-
Neurotrophin 4
- NT5:
-
Neurotrophin 5
- OE:
-
Olfactory epithelium
- OEC:
-
Olfactory ensheathing cell
- OMgp:
-
Oligodendrocyte-myelin glycoprotein
- p75NTR :
-
p75 low-affinity neurotrophin receptor
- PNS:
-
Peripheral nervous system
- SCI:
-
Spinal cord injury
- TROY:
-
TNFRSF expressed on the mouse embryo
- VEGF:
-
Vascular endothelial growth factor
References
Amemori T, Jendelova P, Ruzickova K, Arboleda D, Sykova E (2010) Co-transplantation of olfactory ensheathing glia and mesenchymal stromal cells does not have synergistic effects after spinal cord injury in the rat. Cytotherapy 12:212–225
Antonic A, Sena ES, Lees JS, Wills TE, Skeers P, Batchelor PE, Macleod MR, Howells DW (2013) Stem cell transplantation in traumatic spinal cord injury: a systematic review and meta-analysis of animal studies. PLoS Biol 11:e1001738
Aoki M, Kishima H, Yoshimura K, Ishihara M, Ueno M, Hata K, Yamashita T, Iwatsuki K, Yoshimine T (2010) Limited functional recovery in rats with complete spinal cord injury after transplantation of whole-layer olfactory mucosa: laboratory investigation. J Neurosurg Spine 12:122–130
Arevalo MA, Santos-Galindo M, Bellini MJ, Azcoitia I, Garcia-Segura LM (2010) Actions of estrogens on glial cells: implications for neuroprotection. Biochim Biophys Acta 1800:1106–1112
Au WW, Treloar HB, Greer CA (2002) Sublaminar organization of the mouse olfactory bulb nerve layer. J Comp Neurol 446:68–80
Barbour HR, Plant CD, Harvey AR, Plant GW (2013) Tissue sparing, behavioral recovery, supraspinal axonal sparing/regeneration following sub-acute glial transplantation in a model of spinal cord contusion. BMC Neurosci 14:106
Barraud P, Seferiadis AA, Tyson LD, Zwart MF, Szabo-Rogers HL, Ruhrberg C, Liu KJ, Baker CV (2010) Neural crest origin of olfactory ensheathing glia. Proc Natl Acad Sci U S A 107:21040–21045
Barraud P, St John JA, Stolt CC, Wegner M, Baker CV (2013) Olfactory ensheathing glia are required for embryonic olfactory axon targeting and the migration of gonadotropin-releasing hormone neurons. Biol Open 2:750–759
Bartolomei JC, Greer CA (2000) Olfactory ensheathing cells: bridging the gap in spinal cord injury. Neurosurgery 47:1057–1069
Batzofin BM, Weiss YG, Ledot SF (2013) Do corticosteroids improve outcome for any critical illness? Curr Opin Anesthesio 26:164–170
Beattie MS, Bresnahan JC, Komon J, Tovar CA, Van Meter M, Anderson DK, Faden AI, Hsu CY, Noble LJ, Salzman S, Young W (1997) Endogenous repair after spinal cord contusion injuries in the rat. Exp Neurol 148:453–463
Block ML, Hong JS (2005) Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol 76:77–98
Bolton AE (2005) Biologic effects and basic science of a novel immune-modulation therapy. Am J Cardiol 95:24C–29C; discussion 38C-40C
Boruch AV, Conners JJ, Pipitone M, Deadwyler G, Storer PD, Devries GH, Jones KJ (2001) Neurotrophic and migratory properties of an olfactory ensheathing cell line. Glia 33:225–229
Bunge RP, Bunge MB, Rish H (1960) Electron microscopic study of demyelination in an experimentally induced lesion in adult cat spinal cord. J Biophys Biochem Cytol 7:685–696
Byrnes KR, Stoica B, Riccio A, Pajoohesh-Ganji A, Loane DJ, Faden AI (2009) Activation of metabotropic glutamate receptor 5 improves recovery after spinal cord injury in rodents. Ann Neurol 66:63–74
Cabezas R, El-Bacha RS, Gonzalez J, Barreto GE (2012) Mitochondrial functions in astrocytes: neuroprotective implications from oxidative damage by rotenone. Neurosci Res 74:80–90
Cao L, Liu L, Chen ZY, Wang LM, Ye JL, Qiu HY, Lu CL, He C (2004) Olfactory ensheathing cells genetically modified to secrete GDNF to promote spinal cord repair. Brain 127:535–549
Cao L, Zhu YL, Su ZD, Lv BL, Huang ZH, Mu LF, He C (2007) Olfactory ensheathing cells promote migration of Schwann cells by secreted nerve growth factor. Glia 55:897–904
Centenaro LA, Jaeger MD, Ilha J, de Souza MA, Kalil-Gaspar PI, Cunha NB, Marcuzzo S, Achaval M (2011) Olfactory and respiratory lamina propria transplantation after spinal cord transection in rats: effects on functional recovery and axonal regeneration. Brain Res 1426:54–72
Chatzipanteli K, Garcia R, Marcillo AE, Loor KE, Kraydieh S, Dietrich WD (2002) Temporal and segmental distribution of constitutive and inducible nitric oxide synthases after traumatic spinal cord injury: effect of aminoguanidine treatment. J Neurotrauma 19:639–651
Chehrehasa F, Windus LC, Ekberg JA, Scott SE, Amaya D, Mackay-Sim A, St John JA (2010) Olfactory glia enhance neonatal axon regeneration. Mol Cell Neurosci 45:277–288
Chehrehasa F, Ekberg JA, Lineburg K, Amaya D, Mackay-Sim A, St John JA (2012) Two phases of replacement replenish the olfactory ensheathing cell population after injury in postnatal mice. Glia 60:322–332
Chhabra HS, Lima C, Sachdeva S, Mittal A, Nigam V, Chaturvedi D, Arora M, Aggarwal A, Kapur R, Khan TA (2009) Autologous olfactory [corrected] mucosal transplant in chronic spinal cord injury: an Indian Pilot Study. Spinal Cord 47:887–895
Chuah MI, Zheng DR (1992) The human primary olfactory pathway: fine structural and cytochemical aspects during development and in adults. Microsc Res Tech 23:76–85
Chuah MI, Au C (1994) Olfactory cell-cultures on ensheathing cell monolayers. Chemical Senses 19:25–34
Chuah MI, Teague R (1999) Basic fibroblast growth factor in the primary olfactory pathway: Mitogenic effect on ensheathing cells. Neuroscience 88:1043–1050
Chuah MI, Choi-Lundberg D, Weston S, Vincent AJ, Chung RS, Vickers JC, West AK (2004) Olfactory ensheathing cells promote collateral axonal branching in the injured adult rat spinal cord. Exp Neurol 185:15–25
Chuah MI, Hale DM, West AK (2011) Interaction of olfactory ensheathing cells with other cell types in vitro and after transplantation: glial scars and inflammation. Exp Neurol 229:46–53
Chugani DC, Kedersha NL, Rome LH (1991) Vault immunofluorescence in the brain: new insights regarding the origin of microglia. J Neurosci 11:256–268
Chung RS, Woodhouse A, Fung S, Dickson TC, West AK, Vickers JC, Chuah MI (2004) Olfactory ensheathing cells promote neurite sprouting of injured axons in vitro by direct cellular contact and secretion of soluble factors. Cell Mol Life Sci 61:1238–1245
Chung WS, Barres BA (2012) The role of glial cells in synapse elimination. Curr Opin Neurobiol 22:438–445
Collazos-Castro JE, Muneton-Gomez VC, Nieto-Sampedro M (2005) Olfactory glia transplantation into cervical spinal cord contusion injuries. J Neurosurg-Spine 3:308–317
Doucette JR (1984) The glial cells in the nerve fiber layer of the rat olfactory bulb. Anat Rec 210:385–391
Doucette R (1990) Glial influences on axonal growth in the primary olfactory system. Glia 3:433–449
Doucette R (1995) Olfactory ensheathing cells—potential for glial-cell transplantation into areas of CNS injury. Histol Histopathol 10:503–507
Doucette R (2002) Olfactory ensheathing cells: past, present and future. Faseb J 16:A751–A751
Doucette R, Devon R (1993) Olfactory ensheathing cells—factors influencing the phenotype of these glial-cells. Biol Pathol Astrocyte Neuron Interact 2:117–124
Ekberg JA, Amaya D, Chehrehasa F, Lineburg K, Claxton C, Windus LC, Key B, Mackay-Sim A, St John JA (2011) OMP-ZsGreen fluorescent protein transgenic mice for visualisation of olfactory sensory neurons in vivo and in vitro. J Neurosci Methods 196:88–98
Fairless R, Barnett SC (2005) Olfactory ensheathing cells: their role in central nervous system repair. Int J Biochem Cell Biol 37:693–699
Farbman AI, Squinto LM (1985) Early development of olfactory receptor cell axons. Dev Brain Res 19:205–213
Feron F, Perry C, Cochrane J, Licina P, Nowitzke A, Urquhart S, Geraghty T, Mackay-Sim A (2005) Autologous olfactory ensheathing cell transplantation in human spinal cord injury. Brain 128:2951–2960
Flora G, Joseph G, Patel S, Singh A, Bleicher D, Barakat DJ, Louro J, Fenton S, Garg M, Bunge MB, Pearse DD (2013) Combining neurotrophin-transduced schwann cells and rolipram to promote functional recovery from subacute spinal cord injury. Cell Transplant 22:2203–2217
Friedman JA, Windebank AJ, Yaszemski MJ, Moore MJ, Lewellyn EB (2002a) A Schwann cell-seeded, biodegradable polymer implant for promoting axon regeneration after spinal cord injury. Ann Neurol 52:S87–S87
Friedman JA, Windebank AJ, Moore MJ, Spinner RJ, Currier BL, Yaszemski MJ (2002b) Biodegradable polymer grafts for surgical repair of the injured spinal cord. Neurosurgery 51:742–751
Gao Z, Zhu Q, Zhang Y, Zhao Y, Cai L, Shields CB, Cai J (2013) Reciprocal modulation between microglia and astrocyte in reactive gliosis following the CNS injury. Mol Neurobiol 48:690–701
Garcia-Escudero V, Garcia-Gomez A, Langa E, Martin-Bermejo MJ, Ramirez-Camacho R, Garcia-Berrocal JR, Moreno-Flores MT, Avila J, Lim F (2012) Patient-derived olfactory mucosa cells but not lung or skin fibroblasts mediate axonal regeneration of retinal ganglion neurons. Neurosci Lett 509:27–32
Gong Q, Bailey MS, Pixley SK, Ennis M, Liu W, Shipley MT (1994) Localization and regulation of low affinity nerve growth factor receptor expression in the rat olfactory system during development and regeneration. J Comp Neurol 344:336–348
Granger N, Blamires H, Franklin RJ, Jeffery ND (2012) Autologous olfactory mucosal cell transplants in clinical spinal cord injury: a randomized double-blinded trial in a canine translational model. Brain 135:3227–3237
Graziadei PP, Levine RR, Graziadei GA (1978) Regeneration of olfactory axons and synapse formation in the forebrain after bulbectomy in neonatal mice. Proc Natl Acad Sci U S A 75:5230–5234
Gudino-Cabrera G, Pastor AM, de la Cruz RR, Delgado-Garcia JM, Nieto-Sampedro M (2000) Limits to the capacity of transplants of olfactory glia to promote axonal regrowth in the CNS. Neuroreport 11:467–471
Guest JD, Herrera L, Margitich I, Oliveria M, Marcillo A, Casas CE (2008) Xenografts of expanded primate olfactory ensheathing glia support transient behavioral recovery that is independent of serotonergic or corticospinal axonal regeneration in nude rats following spinal cord transection. Exp Neurol 212:261–274
Hermann GE, Rogers RC, Bresnahan JC, Beattie MS (2001) Tumor necrosis factor-alpha induces cFOS and strongly potentiates glutamate-mediated cell death in the rat spinal cord. Neurobiol Dis 8:590–599
Hisaoka T, Morikawa Y, Kitamura T, Senba E (2004) Expression of a member of tumor necrosis factor receptor superfamily, TROY, in the developing olfactory system. Glia 45:313–324
Huang H, Chen L, Wang H, Xiu B, Li B, Wang R, Zhang J, Zhang F, Gu Z, Li Y, Song Y, Hao W, Pang S, Sun J (2003) Influence of patients’ age on functional recovery after transplantation of olfactory ensheathing cells into injured spinal cord injury. Chin Med J (Engl) 116:1488–1491
Huang H, Wang H, Chen L, Gu Z, Zhang J, Zhang F, Song Y, Li Y, Tan K, Liu Y, Xi H (2006) Influence factors for functional improvement after olfactory ensheathing cell transplantation for chronic spinal cord injury. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 20:434–438
Huang HY, Chen L, Xi HT, Wang HM, Zhang J, Zhang F, Liu YC (2008a) Fetal olfactory ensheathing cells transplantation in amyotrophic lateral sclerosis patients: a controlled pilot study. Clin Transplant 22:710–718
Huang ZH, Wang Y, Cao L, Su ZD, Zhu YL, Chen YZ, Yuan XB, He C (2008b) Migratory properties of cultured olfactory ensheathing cells by single-cell migration assay. Cell Res 18:479–490
Huang HY, Xi HT, Chen L, Zhang F, Liu YC (2012) Long-term outcome of olfactory ensheathing cell therapy for patients with complete chronic spinal cord injury. Cell Transplant 21:21S23–S31
Hulsebosch CE (2002) Recent advances in pathophysiology and treatment of spinal cord injury. Adv Physiol Educ 26:238–255
Hurlbert RJ, Hadley MN, Walters BC, Aarabi B, Dhall SS, Gelb DE, Rozzelle CJ, Ryken TC, Theodore N (2013) Pharmacological therapy for acute spinal cord injury. Neurosurgery 72:93–105
Jauregui-Huerta F, Ruvalcaba-Delgadillo Y, Gonzalez-Castaneda R, Garcia-Estrada J, Gonzalez-Perez O, Luquin S (2010) Responses of glial cells to stress and glucocorticoids. Curr Immunol Rev 6:195–204
Jessen KR (2004) Glial cells. Int J Biochem Cell Biol 36:1861–1867
Jessen KR (2006) A brief look at glial cells. Novartis Found Symp 276:5–14; discussion 54–17, 275–281
Jones DG, Anderson ER, Galvin KA (2003) Spinal cord regeneration: moving tentatively towards new perspectives. Neurorehabilitation 18:339–351
Kafitz KW, Greer CA (1999) Olfactory ensheathing cells promote neurite extension from embryonic olfactory receptor cells in vitro. Glia 25:99–110
Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG (2009) Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci 29:13435–13444
Kriegstein AR, Gotz M (2003) Radial glia diversity: a matter of cell fate. Glia 43:37–43
Lakatos A, Franklin RJM, Barnett SC (2000) Olfactory ensheathing cells and Schwann cells differ in their in vitro interactions with astrocytes. Glia 32:214–225
Lamond R, Barnett SC (2013) Schwann cells but not olfactory ensheathing cells inhibit CNS myelination via the secretion of connective tissue growth factor. J Neurosci 33:18686–18697
Lankford KL, Sasaki M, Radtke C, Kocsis JD (2008) Olfactory ensheathing cells exhibit unique migratory, phagocytic, and myelinating properties in the X-irradiated spinal cord not shared by Schwann cells. Glia 56:1664–1678
Lavdas AA, Chen J, Papastefanaki F, Chen S, Schachner M, Matsas R, Thomaidou D (2010) Schwann cells engineered to express the cell adhesion molecule L1 accelerate myelination and motor recovery after spinal cord injury. Exp Neurol 221:206–216
Leal-Filho MB (2011) Spinal cord injury: from inflammation to glial scar. Surg Neurol Int 2:112
Leung JY, Chapman JA, Harris JA, Hale D, Chung RS, West AK, Chuah MI (2008) Olfactory ensheathing cells are attracted to, and can endocytose, bacteria. Cell Mol Life Sci 65:2732–2739
Li BC, Xu C, Zhang JY, Li Y, Duan ZX (2012) Differing Schwann cells and olfactory ensheathing cells behaviors, from interacting with astrocyte, produce similar improvements in contused rat spinal cord’s motor function. J Mol Neurosci 48:35–44
Li Y, Field PM, Raisman G (1997) Repair of adult rat corticospinal tract by transplants of olfactory ensheathing cells. Science 277:2000–2002
Li Y, Decherchi P, Raisman G (2003) Transplantation of olfactory ensheathing cells into spinal cord lesions restores breathing and climbing. J Neurosci 23:727–731
Li Y, Field PM, Raisman G (2005) Olfactory ensheathing cells and olfactory nerve fibroblasts maintain continuous open channels for regrowth of olfactory nerve fibres. Glia 52:245–251
Li Y, Yamamoto M, Raisman G, Choi D, Carlstedt T (2007) An experimental model of ventral root repair showing the beneficial effect of transplanting olfactory ensheathing cells. Neurosurgery 60:734–740; discussion 740–731
Lim PAC, Tow AM (2007) Recovery and regeneration after spinal cord injury: a review and summary of recent literature. Ann Acad Med Singapore 36:49–57
Lima C, Pratas-Vital J, Escada P, Hasse-Ferreira A, Capucho C, Peduzzi JD (2006) Olfactory mucosa autografts in human spinal cord injury: a pilot clinical study. J Spinal Cord Med 29:191–203
Lopez MV, Cuadrado MP, Ruiz-Poveda OM, Del Fresno AM, Accame ME (2007) Neuroprotective effect of individual ginsenosides on astrocytes primary culture. Biochim Biophys Acta 1770:1308–1316
Lopez-Vales R, Fores J, Verdu E, Navarro X (2006) Acute and delayed transplantation of olfactory ensheathing cells promote partial recovery after complete transection of the spinal cord. Neurobiol Dis 21:57–68
Lu P, Yang H, Culbertson M, Graham L, Roskams AJ, Tuszynski MH (2006) Olfactory ensheathing cells do not exhibit unique migratory or axonal growth-promoting properties after spinal cord injury. J Neurosci 26:11120–11130
Ma YH, Zhang Y, Cao L, Su JC, Wang ZW, Xu AB, Zhang SC (2010) Effect of neurotrophin-3 genetically modified olfactory ensheathing cells transplantation on spinal cord injury. Cell Transplant 19:167–177
Mackay-Sim A, Kittel P (1991a) Cell dynamics in the adult mouse olfactory epithelium: a quantitative autoradiographic study. J Neurosci 11:979–984
Mackay-Sim A, Kittel PW (1991b) On the life span of olfactory receptor neurons. Eur J Neurosci 3:209–215.
Mackay-Sim A, St John JA (2011) Olfactory ensheathing cells from the nose: clinical application in human spinal cord injuries. Exp Neurol 229:174–180
Mackay-Sim A, Feron F, Cochrane J, Bassingthwaighte L, Bayliss C, Davies W, Fronek P, Gray C, Kerr G, Licina P, Nowitzke A, Perry C, Silburn PAS, Urquhart S, Geraghty T (2008) Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial. Brain 131:2376–2386
Matthews MA, St Onge MF, Faciane CL, Gelderd JB (1979) Axon sprouting into segments of rat spinal cord adjacent to the site of a previous transection. Neuropathol Appl Neurobiol 5:181–196
Mayeur A, Duclos C, Honore A, Gauberti M, Drouot L, do Rego JC, Bon-Mardion N, Jean L, Verin E, Emery E, Lemarchant S, Vivien D, Boyer O, Marie JP, Guerout N (2013) Potential of olfactory ensheathing cells from different sources for spinal cord repair. PLoS ONE 8:e62860
Mombaerts P, Wang F, Dulac C, Chao SK, Nemes A, Mendelsohn M, Edmondson J, Axel R (1996) Visualizing an olfactory sensory map. Cell 87:675–686
Munoz-Quiles C, Santos-Benito FF, Liamusi MB, Ramon-Cueto A (2009) Chronic spinal injury repair by olfactory bulb ensheathing glia and feasibility for autologous therapy. J Neuropath Exp Neur 68:1294–1308
Ndubaku U, de Bellard ME (2008) Glial cells: old cells with new twists. Acta Histochem 110:182–195
Novikova LN, Lobov S, Wiberg M, Novikov LN (2011) Efficacy of olfactory ensheathing cells to support regeneration after spinal cord injury is influenced by method of culture preparation. Exp Neurol 229:132–142
Oudega M, Xu XM (2006) Schwann cell transplantation for repair of the adult spinal cord. J Neurotrauma 23:453–467
Panni P, Ferguson IA, Beacham I, Mackay-Sim A, Ekberg JA, St John JA (2013) Phagocytosis of bacteria by olfactory ensheathing cells and Schwann cells. Neurosci Lett 539:65–70
Park HW, Lim MJ, Jung H, Lee SP, Paik KS, Chang MS (2010) Human mesenchymal stem cell-derived Schwann cell-like cells exhibit neurotrophic effects, via distinct growth factor production, in a model of spinal cord injury. Glia 58:1118–1132
Parrinello S, Napoli I, Ribeiro S, Wingfield Digby P, Fedorova M, Parkinson DB, Doddrell RD, Nakayama M, Adams RH, Lloyd AC (2010) EphB signaling directs peripheral nerve regeneration through Sox2-dependent Schwann cell sorting. Cell 143:145–155
Pearse DD, Chatzipanteli K, Marcillo AE, Bunge MB, Dietrich WD (2003) Comparison of iNOS inhibition by antisense and pharmacological inhibitors after spinal cord injury. J Neuropathol Exp Neurol 62:1096–1107
Pfeifer K, Vroemen M, Blesch A, Weidner N (2004) Adult neural progenitor cells provide a permissive guiding substrate for corticospinal axon growth following spinal cord injury. Eur J Neurosci 20:1695–1704
Qiu J, Cai D, Dai H, McAtee M, Hoffman PN, Bregman BS, Filbin MT (2002) Spinal axon regeneration induced by elevation of cyclic AMP. Neuron 34:895–903
Radtke C, Lankford KL, Wewetzer K, Imaizumi T, Fodor WL, Kocsis JD (2010) Impaired spinal cord remyelination by long-term cultured adult porcine olfactory ensheathing cells correlates with altered in vitro phenotypic properties. Xenotransplantation 17:71–80
Raisman G, Li Y (2007) Repair of neural pathways by olfactory ensheathing cells. Nat Rev Neurosci 8:312–319
Ramer LM, Au E, Richter MW, Liu J, Tetzlaff W, Roskams AJ (2004) Peripheral olfactory ensheathing cells reduce scar and cavity formation and promote regeneration after spinal cord injury. J Comp Neurol 473:1–15
Ramon-Cueto A (2000) Olfactory ensheathing glia transplantation into the injured spinal cord. Neural Plast Regen 128:265–272
Ramon-Cueto A (2011) Olfactory ensheathing glia for nervous system repair. Exp Neurol 229:1–1
Ramon-Cueto A, Nieto-Sampedro M (1994) Regeneration into the spinal cord of transected dorsal root axons is promoted by ensheathing glia transplants. Exp Neurol 127:232–244
Ramon-Cueto A, Avila J (1998) Olfactory ensheathing glia: properties and function. Brain Res Bull 46:175–187
Ramon-Cueto A, Santos-Benito FF (2001) Cell therapy to repair injured spinal cords: olfactory ensheathing glia transplantation. Restor Neurol Neuros 19:149–156
Resnick DK, Cechvala CF, Yan Y, Witwer BP, Sun D, Zhang S (2003) Adult olfactory ensheathing cell transplantation for acute spinal cord injury. J Neurotrauma 20:279–285
Richter MW, Fletcher PA, Liu J, Tetzlaff W, Roskams AJ (2005) Lamina propria and olfactory bulb ensheathing cells exhibit differential integration and migration and promote differential axon sprouting in the lesioned spinal cord. J Neurosci 25:10700–10711
Roloff F, Ziege S, Baumgartner W, Wewetzer K, Bicker G (2013) Schwann cell-free adult canine olfactory ensheathing cell preparations from olfactory bulb and mucosa display differential migratory and neurite growth-promoting properties in vitro. BMC Neurosci 14:141
Rubio MP, Munoz-Quiles C, Ramon-Cueto A (2008) Adult olfactory bulbs from primates provide reliable ensheathing glia for cell therapy. Glia 56:539–551
Salehi M, Pasbakhsh P, Soleimani M, Abbasi M, Hasanzadeh G, Modaresi MH, Sobhani A (2009) Repair of spinal cord injury by co-transplantation of embryonic stem cell-derived motor neuron and olfactory ensheathing cell. Iran Biomed J 13:125–135
Santos-Benito FF, Ramon-Cueto A (2003) Olfactory ensheathing glia transplantation: a therapy to promote repair in the mammalian central nervous system. Anat Rec B New Anat 271:77–85
Santos-Silva A, Fairless R, Frame MC, Montague P, Smith GM, Toft A, Riddell JS, Barnett SC (2007) FGF/heparin differentially regulates Schwann cell and olfactory ensheathing cell interactions with astrocytes: a role in astrocytosis. J Neurosci 27:7154–7167
Singh S, Swarnkar S, Goswami P, Nath C (2011) Astrocytes and microglia: responses to neuropathological conditions. Int J Neurosci 121:589–597
St John JA, Ekberg JA, Dando S, Meedeniya ACB, Horton RE, Batzloff M, Owen SJ, Holt S, Peak IR, Ulett G, Mackay-Sim A, Beacham IR (2014) Burkholderia pseudomallei penetrates the brain via destruction of the olfactory and trigeminal nerves: implications for the pathogenesis of neurological melioidosis. mBIO in press
Stahel PF, VanderHeiden T, Finn MA (2012) Management strategies for acute spinal cord injury: current options and future perspectives. Curr Opin Crit Care 18:651–660
Stamegna JC, Felix MS, Roux-Peyronnet J, Rossi V, Feron F, Gauthier P, Matarazzo V (2011) Nasal OEC transplantation promotes respiratory recovery in a subchronic rat model of cervical spinal cord contusion. Exp Neurol 229:120–131
Su Z, He C (2010) Olfactory ensheathing cells: biology in neural development and regeneration. Prog Neurobiol 92:517–532
Su Z, Yuan Y, Chen J, Cao L, Zhu Y, Gao L, Qiu Y, He C (2009) Reactive astrocytes in glial scar attract olfactory ensheathing cells migration by secreted TNF-alpha in spinal cord lesion of rat. PLoS ONE 4:e8141
Su Z, Chen J, Qiu Y, Yuan Y, Zhu F, Zhu Y, Liu X, Pu Y, He C (2013) Olfactory ensheathing cells: the primary innate immunocytes in the olfactory pathway to engulf apoptotic olfactory nerve debris. Glia 61:490–503
Tabakow P, Jarmundowicz W, Czapiga B, Fortuna W, Miedzybrodzki R, Czyz M, Huber J, Szarek D, Okurowski S, Szewczyk P, Gorski A, Raisman G (2013) Transplantation of autologous olfactory ensheathing cells in complete human spinal cord injury. Cell Transplant 22:1591–1612
Teng X, Nagata I, Li HP, Kimura-Kuroda J, Sango K, Kawamura K, Raisman G, Kawano H (2008) Regeneration of nigrostriatal dopaminergic axons after transplantation of olfactory ensheathing cells and fibroblasts prevents fibrotic scar formation at the lesion site. J Neurosci Res 86:3140–3150
Tennent R, Chuah MI (1996) Ultrastructural study of ensheathing cells in early development of olfactory axons. Brain Res Dev Brain Res 95:135–139
Tharion G, Indirani K, Durai M, Meenakshi M, Devasahayam SR, Prabhav NR, Solomons C, Bhattacharji S (2011) Motor recovery following olfactory ensheathing cell transplantation in rats with spinal cord injury. Neurol India 59:77–83
Tisay KT, Key B (1999) The extracellular matrix modulates olfactory neurite outgrowth on ensheathing cells. J Neurosci 19:9890–9899
Toft A, Scott DT, Barnett SC, Riddell JS (2007) Electrophysiological evidence that olfactory cell transplants improve function after spinal cord injury. Brain 130:970–984
Toft A, Tome M, Barnett SC, Riddell JS (2013) A comparative study of glial and non-neural cell properties for transplant-mediated repair of the injured spinal cord. Glia 61:513–528
Torres-Espin A, Redondo-Castro E, Hernandez J, Navarro X (2014) Bone marrow mesenchymal stromal cells and olfactory ensheathing cells transplantation after spinal cord injury—a morphological and functional comparison in rats. Eur J Neurosci 39:1701–1717
Ubink R, Hokfelt T (2000) Expression of neuropeptide Y in olfactory ensheathing cells during prenatal development. J Comp Neurol 423:13–25
Valverde F, Santacana M, Heredia M (1992) Formation of an olfactory glomerulus: morphological aspects of development and organization. Neuroscience 49:255–275
Vassar R, Chao SK, Sitcheran R, Nunez JM, Vosshall LB, Axel R (1994) Topographic organization of sensory projections to the olfactory bulb. Cell 79:981–991
Vincent AJ, West AK, Chuah MI (2003) Morphological plasticity of olfactory ensheathing cells is regulated by cAMP and endothelin-1. Glia 41:393–403
Vincent AJ, West AK, Chuah MI (2005a) Morphological and functional plasticity of olfactory ensheathing cells. J Neurocytol 34:65–80
Vincent AJ, Taylor JM, Choi-Lundberg DL, West AK, Chuah MI (2005b) Genetic expression profile of olfactory ensheathing cells is distinct from that of Schwann cells and astrocytes. Glia 51:132–147
Vroemen M, Caioni M, Bogdahn U, Weidner N (2007) Failure of Schwann cells as supporting cells for adult neural progenitor cell grafts in the acutely injured spinal cord. Cell Tissue Res 327:1–13
Vukovic J, Ruitenberg MJ, Roet K, Franssen E, Arulpragasam A, Sasaki T, Verhaagen J, Harvey AR, Busfield SJ, Plant GW (2009) The glycoprotein Fibulin-3 regulates morphology and motility of olfactory ensheathing cells in vitro. Glia 57:424–443
Wewetzer K, Kern N, Ebel C, Radtke C, Brandes G (2005) Phagocytosis of O4+ axonal fragments in vitro by p75- neonatal rat olfactory ensheathing cells. Glia 49:577–587
Whitesides JG 3rd, LaMantia AS (1996) Differential adhesion and the initial assembly of the mammalian olfactory nerve. J Comp Neurol 373:240–254
Windus LC, Claxton C, Allen CL, Key B, St John JA (2007) Motile membrane protrusions regulate cell-cell adhesion and migration of olfactory ensheathing glia. Glia 55:1708–1719
Windus LC, Lineburg KE, Scott SE, Claxton C, Mackay-Sim A, Key B, St John JA (2010) Lamellipodia mediate the heterogeneity of central olfactory ensheathing cell interactions. Cell Mol Life Sci 67:1735–1750
Windus LC, Chehrehasa F, Lineburg KE, Claxton C, Mackay-Sim A, Key B, St John JA (2011) Stimulation of olfactory ensheathing cell motility enhances olfactory axon growth. Cell Mol Life Sci 68:3233–3247
Woodhall E, West AK, Chuah MI (2001) Cultured olfactory ensheathing cells express nerve growth factor, brain-derived neurotrophic factor, glia cell line-derived neurotrophic factor and their receptors. Mol Brain Res 88:203–213
Woodhall E, West AK, Vickers JC, Chuah MI (2003) Olfactory ensheathing cell phenotype following implantation in the lesioned spinal cord. Cell Mol Life Sci 60:2241–2253
Wu J, Sun TS, Ren JX, Wang XZ (2008) Ex vivo non-viral vector-mediated neurotrophin-3 gene transfer to olfactory ensheathing glia: effects on axonal regeneration and functional recovery after implantation in rats with spinal cord injury. Neurosci Bull 24:57–65
Wu XJ, Bolger WE, Anders JJ (2013) Fibroblasts isolated from human middle turbinate mucosa cause neural progenitor cells to differentiate into glial lineage cells. PLoS ONE 8 e76926
Xu XH, Zhou JF, Li TZ, Zhang ZH, Shan L, Xiang ZH, Yu ZW, Zhang WD, He C (2009) Polygalasaponin G promotes neurite outgrowth of cultured neuron on myelin. Neurosci Lett 460:41–46
Yamamoto M, Raisman G, Li DQ, Li Y (2009) Transplanted olfactory mucosal cells restore paw reaching function without regeneration of severed corticospinal tract fibres across the lesion. Brain Res 1303:26–31
Yan H, Bunge MB, Wood PM, Plant GW (2001) Mitogenic response of adult rat olfactory ensheathing glia to four growth factors. Glia 33:334–342
Zhang SX, Huang FF, Gates M, Holmberg EG (2011) Scar ablation combined with LP/OEC transplantation promotes anatomical recovery and P0-positive myelination in chronically contused spinal cord of rats. Brain Res 1399:1–14
Ziege S, Baumgartner W, Wewetzer K (2013) Toward defining the regenerative potential of olfactory mucosa: establishment of Schwann cell-free adult canine olfactory ensheathing cell preparations suitable for transplantation. Cell Transplant 22:355–367
Ziegler MD, Hsu D, Takeoka A, Zhong H, Ramon-Cueto A, Phelps PE, Roy RR, Edgerton VR (2011) Further evidence of olfactory ensheathing glia facilitating axonal regeneration after a complete spinal cord transection. Exp Neurol 229:109–119
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Tello Velasquez, J., Ekberg, J., St John, J. (2015). Transplantation of Olfactory Ensheathing Cells in Spinal Cord Injury. In: Zhao, LR., Zhang, J. (eds) Cellular Therapy for Stroke and CNS Injuries. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-319-11481-1_13
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