Skip to main content

Advertisement

Log in

The Anti-inflammation Property of Olfactory Ensheathing Cells in Neural Regeneration After Spinal Cord Injury

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Neural regeneration has troubled investigators worldwide in the past decades. Currently, cell transplantation emerged as a breakthrough targeted therapy for spinal cord injury (SCI) in the neurotrauma field, which provides a promising strategy in neural regeneration. Olfactory ensheathing cells (OECs), a specialized type of glial cells, is considered as the excellent candidate due to its unique variable and intrinsic regeneration-supportive properties. In fact, OECs could support olfactory receptor neuron turnover and axonal extension, which is essential to maintain the function of olfactory nervous system. Hitherto, an increasing number of literatures demonstrate that transplantation of OECs exerts vital roles in neural regeneration and functional recovery after neural injury, including central and peripheral nervous system. It is common knowledge that the deteriorating microenvironment (ischemia, hypoxia, scar, acute and chronic inflammation, etc.) resulting from injured nervous system is adverse for neural regeneration. Interestingly, recent studies indicated that OECs could promote neural repair through improvement of the disastrous microenvironments, especially to the overwhelmed inflammatory responses. Although OECs possess unusual advantages over other cells for neural repair, particularly in SCI, the mechanisms of OEC-mediated neural repair are still controversial with regard to anti-inflammation. Therefore, it is significant to summarize the anti-inflammation property of OECs, which is helpful to understand the biological characteristics of OECs and drive future studies. Here, we mainly focus on the anti-inflammatory role of OECs to make systematic review and discuss OEC-based therapy for CNS injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data Availability

Not applicable.

References

  1. Kadomatsu K, Sakamoto K (2014) Mechanisms of axon regeneration and its inhibition: roles of sulfated glycans. Arch Biochem Biophys 558:36–41. https://doi.org/10.1016/j.abb.2014.06.009

    Article  CAS  PubMed  Google Scholar 

  2. Yang H, He B, Hao D (2015) Biological roles of olfactory ensheathing cells in facilitating neural regeneration: a systematic review. Mol Neurobiol 51:168–179. https://doi.org/10.1007/s12035-014-8664-2

    Article  CAS  PubMed  Google Scholar 

  3. Mahar M, Cavalli V (2018) Intrinsic mechanisms of neuronal axon regeneration. Nat Rev Neurosci 19:323–337. https://doi.org/10.1038/s41583-018-0001-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. L Ee BB, Cripps RA, Fitzharris M and Wing PC (2013) The global map for traumatic spinal cord injury epidemiology: update 2011, global incidence rate. Spinal Cord 52.

  5. Mackay-Sim A, Féron F, Cochrane J, Bassingthwaighte L, Bayliss C, Davies W, Fronek P, Gray C, Kerr G, Licina P, Nowitzke A, Perry C, Silburn P, Urquhart S, Geraghty T (2008) Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial. Brain : J Neurol 131:2376–2386. https://doi.org/10.1093/brain/awn173

    Article  CAS  Google Scholar 

  6. Satti H, Waheed A, Ahmed P, Ahmed K, Akram Z, Aziz T, Satti T, Shahbaz N, Khan M, Malik S (2016) Autologous mesenchymal stromal cell transplantation for spinal cord injury: a phase I pilot study. Cytotherapy 18:518–522. https://doi.org/10.1016/j.jcyt.2016.01.004

    Article  PubMed  Google Scholar 

  7. Curtis E, Martin J, Gabel B, Sidhu N, Rzesiewicz T, Mandeville R, Van Gorp S, Leerink M, Tadokoro T, Marsala S, Jamieson C, Marsala M, Ciacci J (2018) A first-in-human, phase I study of neural stem cell transplantation for chronic spinal cord injury. Cell Stem Cell 22:941-950.e6. https://doi.org/10.1016/j.stem.2018.05.014

    Article  CAS  PubMed  Google Scholar 

  8. Assinck P, Duncan G, Hilton B, Plemel J, Tetzlaff W (2017) Cell transplantation therapy for spinal cord injury. Nat Neurosci 20:637–647. https://doi.org/10.1038/nn.4541

    Article  CAS  PubMed  Google Scholar 

  9. Guo J, Cao G, Yang G, Zhang Y, Wang Y, Song W, Xu Y, Ma T, Liu R, Zhang Q, Hao D, Yang H (2020) Transplantation of activated olfactory ensheathing cells by curcumin strengthens regeneration and recovery of function after spinal cord injury in rats. Cytotherapy 22:301–312. https://doi.org/10.1016/j.jcyt.2020.03.002

    Article  CAS  PubMed  Google Scholar 

  10. Wang G, Cheng Z, Yuan P, Li H, He X (2021) Olfactory ensheathing cell transplantation alters the expression of chondroitin sulfate proteoglycans and promotes axonal regeneration after spinal cord injury. Neural Regen Res 16:1638–1644. https://doi.org/10.4103/1673-5374.301023

    Article  PubMed  PubMed Central  Google Scholar 

  11. Oyinbo C (2011) Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp 71:281–299

    Google Scholar 

  12. Xue M, Yong V (2020) Neuroinflammation in intracerebral haemorrhage: immunotherapies with potential for translation. Lancet Neurol 19:1023–1032. https://doi.org/10.1016/s1474-4422(20)30364-1

    Article  CAS  PubMed  Google Scholar 

  13. Sun X, Jones Z, Chen X, Zhou L, So K, Ren Y (2016) Multiple organ dysfunction and systemic inflammation after spinal cord injury: a complex relationship. J Neuroinflammation 13:260. https://doi.org/10.1186/s12974-016-0736-y

    Article  PubMed  PubMed Central  Google Scholar 

  14. Varela MLO, Mogildea M, Moreno I and Lopes A (2018) Acute inflammation and metabolism. Inflammation.

  15. Mollaei M, Abbasi A, Hassan Z, Pakravan N (2020) The intrinsic and extrinsic elements regulating inflammation. Life Sci 260:118258. https://doi.org/10.1016/j.lfs.2020.118258

    Article  CAS  PubMed  Google Scholar 

  16. Ren Y, Young W (2013) Managing inflammation after spinal cord injury through manipulation of macrophage function. Neural Plast 2013:945034. https://doi.org/10.1155/2013/945034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhou X, He X, Ren Y (2014) Function of microglia and macrophages in secondary damage after spinal cord injury. Neural Regen Res 9:1787–1795. https://doi.org/10.4103/1673-5374.143423

    Article  PubMed  PubMed Central  Google Scholar 

  18. Anwar M, Al Shehabi T, Eid A (2016) Inflammogenesis of secondary spinal cord injury. Front Cell Neurosci 10:98. https://doi.org/10.3389/fncel.2016.00098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hasturk A, Atalay B, Calisaneller T, Ozdemir O, Oruckaptan H, Altinors N (2009) Analysis of serum pro-inflammatory cytokine levels after rat spinal cord ischemia/reperfusion injury and correlation with tissue damage. Turk Neurosurg 19:353–359

    PubMed  Google Scholar 

  20. Hu J, Shi L, Chen Y, Xie X, Zhang N, Zhu A, Jiang Z, Feng Y, Zhang C, Xi J, Lü H (2016) Differential effects of myelin basic protein-activated Th1 and Th2 cells on the local immune microenvironment of injured spinal cord. Exp Neurol 277:190–201. https://doi.org/10.1016/j.expneurol.2016.01.002

    Article  CAS  PubMed  Google Scholar 

  21. Anthony DC, Couch Y (2014) The systemic response to CNS injury. Exp Neurol 258:105–111

    Article  CAS  Google Scholar 

  22. Myers S, Gobejishvili L, Saraswat Ohri S, Garrett Wilson C, Andres K, Riegler A, Donde H, Joshi-Barve S, Barve S, Whittemore S (2019) Following spinal cord injury, PDE4B drives an acute, local inflammatory response and a chronic, systemic response exacerbated by gut dysbiosis and endotoxemia. Neurobiol Dis 124:353–363. https://doi.org/10.1016/j.nbd.2018.12.008

    Article  CAS  PubMed  Google Scholar 

  23. Lin S, Xu C, Hu H, Zhang C, Mei C (2021) Regulation of inflammatory cytokines for spinal cord injury recovery. Histol Histopathol 36:137–142. https://doi.org/10.14670/hh-18-262

    Article  CAS  PubMed  Google Scholar 

  24. Wang D, Zhao S, Pan J, Wang Z, Li Y, Xu X, Yang J, Zhang X, Wang Y, Liu M (2021) Ginsenoside Rb1 attenuates microglia activation to improve spinal cord injury via microRNA-130b-5p/TLR4/NF-κB axis. J Cell Physiol 236:2144–2155. https://doi.org/10.1002/jcp.30001

    Article  CAS  PubMed  Google Scholar 

  25. Wewetzer K, Verdú E, Angelov D, Navarro X (2002) Olfactory ensheathing glia and Schwann cells: two of a kind? Cell Tissue Res 309:337–345. https://doi.org/10.1007/s00441-002-0607-y

    Article  PubMed  Google Scholar 

  26. Su Z, He C (2010) Olfactory ensheathing cells: biology in neural development and regeneration. Prog Neurobiol 92:517–532. https://doi.org/10.1016/j.pneurobio.2010.08.008

    Article  PubMed  Google Scholar 

  27. Barton M, John J, Clarke M, Wright A and Ekberg J (2017) The glia response after peripheral nerve injury: a comparison between schwann cells and olfactory ensheathing cells and their uses for neural regenerative therapies. Int J MolSci 18.https://doi.org/10.3390/ijms18020287

  28. Barraud P, Seferiadis A, Tyson L, Zwart M, Szabo-Rogers H, Ruhrberg C, Liu K, Baker C (2010) Neural crest origin of olfactory ensheathing glia. Proc Natl Acad Sci USA 107:21040–21045. https://doi.org/10.1073/pnas.1012248107

    Article  PubMed  PubMed Central  Google Scholar 

  29. Forni P, Wray S (2012) Neural crest and olfactory system: new prospective. Mol Neurobiol 46:349–360. https://doi.org/10.1007/s12035-012-8286-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Suzuki J, Osumi N (2015) Neural crest and placode contributions to olfactory development. Curr Top Dev Biol 111:351–374. https://doi.org/10.1016/bs.ctdb.2014.11.010

    Article  CAS  PubMed  Google Scholar 

  31. Pellitteri R, Spatuzza M, Stanzani S, Zaccheo D (2010) Biomarkers expression in rat olfactory ensheathing cells. Front Biosci (Schol Ed) 2:289–298. https://doi.org/10.2741/s64

    Article  Google Scholar 

  32. Lee M, Calle E, Brennan A, Ahmed S, Sviderskaya E, Jessen K, Mirsky R (2001) In early development of the rat mRNA for the major myelin protein P(0) is expressed in nonsensory areas of the embryonic inner ear, notochord, enteric nervous system, and olfactory ensheathing cells. Dev Dyn: Off Publ Am Assoc Anatomists 222:40–51. https://doi.org/10.1002/dvdy.1165

    Article  CAS  Google Scholar 

  33. Boyd J, Jahed A, McDonald T, Krol K, Van Eyk J, Doucette R, Kawaja M (2006) Proteomic evaluation reveals that olfactory ensheathing cells but not Schwann cells express calponin. Glia 53:434–440. https://doi.org/10.1002/glia.20299

    Article  PubMed  Google Scholar 

  34. Jahed A, Rowland J, McDonald T, Boyd J, Doucette R, Kawaja M (2007) Olfactory ensheathing cells express smooth muscle alpha-actin in vitro and in vivo. J Comp Neurol 503:209–223. https://doi.org/10.1002/cne.21385

    Article  CAS  PubMed  Google Scholar 

  35. Nazareth L, Shelper T, Chacko A, Basu S, Delbaz A, Lee J, Chen M, St John J, Ekberg J (2020) Key differences between olfactory ensheathing cells and Schwann cells regarding phagocytosis of necrotic cells: implications for transplantation therapies. Sci Rep 10:18936. https://doi.org/10.1038/s41598-020-75850-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Lakatos A, Franklin R, Barnett S (2000) Olfactory ensheathing cells and Schwann cells differ in their in vitro interactions with astrocytes. Glia 32:214–225. https://doi.org/10.1002/1098-1136(200012)32:3%3c214::aid-glia20%3e3.0.co;2-7

    Article  CAS  PubMed  Google Scholar 

  37. Franssen E, Roet K, de Bree F, Verhaagen J (2009) Olfactory ensheathing glia and Schwann cells exhibit a distinct interaction behavior with meningeal cells. J Neurosci Res 87:1556–1564. https://doi.org/10.1002/jnr.21979

    Article  CAS  PubMed  Google Scholar 

  38. Lankford K, Sasaki M, Radtke C, Kocsis J (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. https://doi.org/10.1002/glia.20718

    Article  PubMed  Google Scholar 

  39. Kumar R, Hayat S, Felts P, Bunting S, Wigley C (2005) Functional differences and interactions between phenotypic subpopulations of olfactory ensheathing cells in promoting CNS axonal regeneration. Glia 50:12–20. https://doi.org/10.1002/glia.20154

    Article  PubMed  Google Scholar 

  40. Guérout N, Derambure C, Drouot L, Bon-Mardion N, Duclos C, Boyer O, Marie J (2010) Comparative gene expression profiling of olfactory ensheathing cells from olfactory bulb and olfactory mucosa. Glia 58:1570–1580. https://doi.org/10.1002/glia.21030

    Article  PubMed  Google Scholar 

  41. Honoré A, Le Corre S, Derambure C, Normand R, Duclos C, Boyer O, Marie J, Guérout N (2012) Isolation, characterization, and genetic profiling of subpopulations of olfactory ensheathing cells from the olfactory bulb. Glia 60:404–413. https://doi.org/10.1002/glia.22274

    Article  PubMed  Google Scholar 

  42. Lima C, Escada P, Pratas-Vital J, Branco C, Arcangeli C, Lazzeri G, Maia C, Capucho C, Hasse-Ferreira A, Peduzzi J (2010) Olfactory mucosal autografts and rehabilitation for chronic traumatic spinal cord injury. Neurorehabil Neural Repair 24:10–22. https://doi.org/10.1177/1545968309347685

    Article  PubMed  Google Scholar 

  43. 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. https://doi.org/10.3727/096368912x663532

    Article  PubMed  Google Scholar 

  44. Chen L, Huang H, Xi H, Zhang F, Liu Y, Chen D and Xiao J (2014) A prospective randomized double-blind clinical trial using a combination of olfactory ensheathing cells and Schwann cells for the treatment of chronic complete spinal cord injuries. Cell Transplant:S35–44. https://doi.org/10.3727/096368914x685014

  45. Chuah M, West A (2002) Cellular and molecular biology of ensheathing cells. Microsc Res Tech 58:216–227. https://doi.org/10.1002/jemt.10151

    Article  CAS  PubMed  Google Scholar 

  46. Smith K, Whitcroft K, Law S, Andrews P, Choi D, Jagger D (2020) Olfactory ensheathing cells from the nasal mucosa and olfactory bulb have distinct membrane properties. J Neurosci Res 98:888–901. https://doi.org/10.1002/jnr.24566

    Article  CAS  PubMed  Google Scholar 

  47. Ramón-Cueto A, Avila J (1998) Olfactory ensheathing glia: properties and function. Brain Res Bull 46:175–187. https://doi.org/10.1016/s0361-9230(97)00463-2

    Article  PubMed  Google Scholar 

  48. Khankan R, Wanner I, Phelps P (2015) Olfactory ensheathing cell-neurite alignment enhances neurite outgrowth in scar-like cultures. Exp Neurol 269:93–101. https://doi.org/10.1016/j.expneurol.2015.03.025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Zhang L, Zhuang X, Chen Y, Xia H (2019) Intravenous transplantation of olfactory bulb ensheathing cells for a spinal cord hemisection injury rat model. Cell Transplant 28:1585–1602. https://doi.org/10.1177/0963689719883842

    Article  PubMed  PubMed Central  Google Scholar 

  50. Chio J, Punjani N, Hejrati N, Zavvarian M, Hong J and Fehlings M (2021) Extracellular matrix and oxidative stress following traumatic spinal cord injury: physiological and pathophysiological roles and opportunities for therapeutic intervention. Antioxid Redox Signalhttps://doi.org/10.1089/ars.2021.0120

  51. Orr M, Gensel J (2018) Spinal cord injury scarring and inflammation: therapies targeting glial and inflammatory responses. Neurother : J Am Soc Experiment NeuroTher 15:541–553. https://doi.org/10.1007/s13311-018-0631-6

    Article  CAS  Google Scholar 

  52. David S, Kroner A (2011) Repertoire of microglial and macrophage responses after spinal cord injury. Nat Rev Neurosci 12:388–399. https://doi.org/10.1038/nrn3053

    Article  CAS  PubMed  Google Scholar 

  53. Yu S, Li Z, Xu X, Yao F, Luo Y, Liu Y, Cheng L, Zheng M, Jing J (2022) M1-type microglia can induce astrocytes to deposit chondroitin sulfate proteoglycan after spinal cord injury. Neural Regen Res 17:1072–1079. https://doi.org/10.4103/1673-5374.324858

    Article  PubMed  Google Scholar 

  54. Benowitz L, Popovich P (2011) Inflammation and axon regeneration. Curr Opin Neurol 24:577–583. https://doi.org/10.1097/WCO.0b013e32834c208d

    Article  CAS  PubMed  Google Scholar 

  55. David S, Zarruk J, Ghasemlou N (2012) Inflammatory pathways in spinal cord injury. Int Rev Neurobiol 106:127–152. https://doi.org/10.1016/b978-0-12-407178-0.00006-5

    Article  CAS  PubMed  Google Scholar 

  56. Nan B, Getchell M, Partin J, Getchell T (2001) Leukemia inhibitory factor, interleukin-6, and their receptors are expressed transiently in the olfactory mucosa after target ablation. J Comp Neurol 435:60–77. https://doi.org/10.1002/cne.1193

    Article  CAS  PubMed  Google Scholar 

  57. Getchell T, Shah D, Partin J, Subhedar N, Getchell M (2002) Leukemia inhibitory factor mRNA expression is upregulated in macrophages and olfactory receptor neurons after target ablation. J Neurosci Res 67:246–254. https://doi.org/10.1002/jnr.10090

    Article  CAS  PubMed  Google Scholar 

  58. Gadient R, Patterson P (1999) Leukemia inhibitory factor, interleukin 6, and other cytokines using the GP130 transducing receptor: roles in inflammation and injury. Stem Cells (Dayton, Ohio) 17:127–137. https://doi.org/10.1002/stem.170127

    Article  CAS  Google Scholar 

  59. Williams S, Franklin R, Barnett S (2004) Response of olfactory ensheathing cells to the degeneration and regeneration of the peripheral olfactory system and the involvement of the neuregulins. J Comp Neurol 470:50–62. https://doi.org/10.1002/cne.11045

    Article  CAS  PubMed  Google Scholar 

  60. Vincent A, Taylor J, Choi-Lundberg D, West A, Chuah M (2005) Genetic expression profile of olfactory ensheathing cells is distinct from that of Schwann cells and astrocytes. Glia 51:132–147. https://doi.org/10.1002/glia.20195

    Article  PubMed  Google Scholar 

  61. Franssen E, De Bree F, Essing A, Ramon-Cueto A, Verhaagen J (2008) Comparative gene expression profiling of olfactory ensheathing glia and Schwann cells indicates distinct tissue repair characteristics of olfactory ensheathing glia. Glia 56:1285–1298. https://doi.org/10.1002/glia.20697

    Article  PubMed  Google Scholar 

  62. Finneran D, Nash K (2019) Neuroinflammation and fractalkine signaling in Alzheimer’s disease. J Neuroinflammation 16:30. https://doi.org/10.1186/s12974-019-1412-9

    Article  PubMed  PubMed Central  Google Scholar 

  63. Yan Y, Su J and Zhang Z (2021) The CXCL12/CXCR4/ACKR3 Response axis in chronic neurodegenerative disorders of the central nervous system: therapeutic target and biomarker. Cell MolNeurobiol.https://doi.org/10.1007/s10571-021-01115-1

  64. Hisaoka T, Morikawa Y, Kitamura T, Senba E (2003) Expression of a member of tumor necrosis factor receptor superfamily, TROY, in the developing mouse brain. Brain Res Dev Brain Res 143:105–109. https://doi.org/10.1016/s0165-3806(03)00101-9

    Article  CAS  PubMed  Google Scholar 

  65. 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. https://doi.org/10.1002/glia.10323

    Article  PubMed  Google Scholar 

  66. Tang R, Botchway B, Meng Y, Zhang Y, Zhou C, Jiang J, Liu X (2020) The inhibition of inflammatory signaling pathway by secretory leukocyte protease inhibitor can improve spinal cord injury. Cell Mol Neurobiol 40:1067–1073. https://doi.org/10.1007/s10571-020-00799-1

    Article  CAS  PubMed  Google Scholar 

  67. Xu L, Botchway B, Zhang S, Zhou J, Liu X (2018) Inhibition of NF-κB signaling pathway by resveratrol improves spinal cord injury. Front Neurosci 12:690. https://doi.org/10.3389/fnins.2018.00690

    Article  PubMed  PubMed Central  Google Scholar 

  68. Fan H, Tang H, Shan L, Liu S, Huang D, Chen X, Chen Z, Yang M, Yin X, Yang H, Hao D (2019) Quercetin prevents necroptosis of oligodendrocytes by inhibiting macrophages/microglia polarization to M1 phenotype after spinal cord injury in rats. J Neuroinflammation 16:206. https://doi.org/10.1186/s12974-019-1613-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Fan H, Tang H, Chen Z, Wang H, Zhang L, Jiang Y, Li T, Yang C, Wang X, Li X, Wu S, Zhang G (2020) Inhibiting HMGB1-RAGE axis prevents pro-inflammatory macrophages/microglia polarization and affords neuroprotection after spinal cord injury. J Neuroinflammation 17:295. https://doi.org/10.1186/s12974-020-01973-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Chuah M, Hale D, West A (2011) Interaction of olfactory ensheathing cells with other cell types in vitro and after transplantation: glial scars and inflammation. Exp Neurol 229:46–53. https://doi.org/10.1016/j.expneurol.2010.08.012

    Article  PubMed  Google Scholar 

  71. Nakajima H, Honjoh K, Watanabe S, Kubota A, Matsumine A (2020) Distribution and polarization of microglia and macrophages at injured sites and the lumbar enlargement after spinal cord injury. Neurosci Lett 737:135152. https://doi.org/10.1016/j.neulet.2020.135152

    Article  CAS  PubMed  Google Scholar 

  72. Ding Y, Zhang D, Wang S, Zhang X, Yang J (2021) Hematogenous macrophages: a new therapeutic target for spinal cord injury. Front Cell Dev Biol 9:767888. https://doi.org/10.3389/fcell.2021.767888

    Article  PubMed  PubMed Central  Google Scholar 

  73. López-Vales R, García-Alías G, Forés J, Vela J, Navarro X, Verdú E (2004) Transplanted olfactory ensheathing cells modulate the inflammatory response in the injured spinal cord. Neuron Glia Biol 1:201–209. https://doi.org/10.1017/s1740925x05000037

    Article  PubMed  Google Scholar 

  74. López-Vales R, Forés J, Verdú 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. https://doi.org/10.1016/j.nbd.2005.06.011

    Article  CAS  PubMed  Google Scholar 

  75. López-Vales R, Forés J, Navarro X, Verdú E (2007) Chronic transplantation of olfactory ensheathing cells promotes partial recovery after complete spinal cord transection in the rat. Glia 55:303–311. https://doi.org/10.1002/glia.20457

    Article  PubMed  Google Scholar 

  76. He B, Xie S, Wu M, Hao D, Yang H (2014) Phagocytic removal of neuronal debris by olfactory ensheathing cells enhances neuronal survival and neurite outgrowth via p38MAPK activity. Mol Neurobiol 49:1501–1512. https://doi.org/10.1007/s12035-013-8588-2

    Article  CAS  PubMed  Google Scholar 

  77. Liu S, Zou Y, Belegu V, Lv L, Lin N, Wang T, McDonald J, Zhou X, Xia Q, Wang T (2014) Co-grafting of neural stem cells with olfactory en sheathing cells promotes neuronal restoration in traumatic brain injury with an anti-inflammatory mechanism. J Neuroinflammation 11:66. https://doi.org/10.1186/1742-2094-11-66

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Zhou Y, Liu Z, Liu Z, Chen S, Li M, Shahveranov A, Ye D, Tian Y (2016) Interleukin-6: an emerging regulator of pathological pain. J Neuroinflammation 13:141. https://doi.org/10.1186/s12974-016-0607-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Zhang J, Chen H, Duan Z, Chen K, Liu Z, Zhang L, Yao D, Li B (2017) The effects of co-transplantation of olfactory ensheathing cells and schwann cells on local inflammation environment in the contused spinal cord of rats. Mol Neurobiol 54:943–953. https://doi.org/10.1007/s12035-016-9709-5

    Article  CAS  PubMed  Google Scholar 

  80. Khankan R, Griffis K, Haggerty-Skeans J, Zhong H, Roy R, Edgerton V, Phelps P (2016) Olfactory ensheathing cell transplantation after a complete spinal cord transection mediates neuroprotective and immunomodulatory mechanisms to facilitate regeneration. J Neurosci : Off J Soc Neurosci 36:6269–6286. https://doi.org/10.1523/jneurosci.0085-16.2016

    Article  CAS  Google Scholar 

  81. Delarue Q, Robac A, Massardier R, Marie J, Guérout N (2021) Comparison of the effects of two therapeutic strategies based on olfactory ensheathing cell transplantation and repetitive magnetic stimulation after spinal cord injury in female mice. J Neurosci Res 99:1835–1849. https://doi.org/10.1002/jnr.24836

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Xie J, Li Y, Dai J, He Y, Sun D, Dai C, Xu H, Yin Z (2019) Olfactory ensheathing cells grafted into the retina of RCS rats suppress inflammation by down-regulating the JAK/STAT Pathway. Front Cell Neurosci 13:341. https://doi.org/10.3389/fncel.2019.00341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Mothe A, Bozkurt G, Catapano J, Zabojova J, Wang X, Keating A, Tator C (2011) Intrathecal transplantation of stem cells by lumbar puncture for thoracic spinal cord injury in the rat. Spinal Cord 49:967–973. https://doi.org/10.1038/sc.2011.46

    Article  CAS  PubMed  Google Scholar 

  84. White S, Czisch C, Han M, Plant C, Harvey A, Plant G (2016) Intravenous transplantation of mesenchymal progenitors distribute solely to the lungs and improve outcomes in cervical spinal cord injury. Stem Cells (Dayton, Ohio) 34:1812–1825. https://doi.org/10.1002/stem.2364

    Article  CAS  Google Scholar 

  85. Zhang L, Zhuang X, Kotitalo P, Keller T, Krzyczmonik A, Haaparanta-Solin M, Solin O, Forsback S, Grönroos T, Han C, López-Picón F, Xia H (2021) viaIntravenous transplantation of olfactory ensheathing cells reduces neuroinflammation after spinal cord injury interleukin-1 receptor antagonist. Theranostics 11:1147–1161. https://doi.org/10.7150/thno.52197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Yan H, Lu D, Rivkees S (2003) Lysophosphatidic acid regulates the proliferation and migration of olfactory ensheathing cells in vitro. Glia 44:26–36. https://doi.org/10.1002/glia.10265

    Article  PubMed  Google Scholar 

  87. Hao D, Liu C, Zhang L, Chen B, Zhang Q, Zhang R, An J, Zhao J, Wu M, Wang Y, Simental A, He B, Yang H (2017) Lipopolysaccharide and curcumin co-stimulation potentiates olfactory ensheathing cell phagocytosis via enhancing their activation. Neurother : J Am Soc Experiment NeuroTher 14:502–518. https://doi.org/10.1007/s13311-016-0485-8

    Article  CAS  Google Scholar 

  88. Wang X, Jiang C, Zhang Y, Chen Z, Fan H, Zhang Y, Wang Z, Tian F, Li J, Yang H, Hao D (2022) The promoting effects of activated olfactory ensheathing cells on angiogenesis after spinal cord injury through the PI3K/Akt pathway. Cell Biosci 12:23. https://doi.org/10.1186/s13578-022-00765-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Gu M, Gao Z, Li X, Guo L, Lu T, Li Y, He X (2017) Conditioned medium of olfactory ensheathing cells promotes the functional recovery and axonal regeneration after contusive spinal cord injury. Brain Res 1654:43–54. https://doi.org/10.1016/j.brainres.2016.10.023

    Article  CAS  PubMed  Google Scholar 

  90. Fan H, Chen Z, Tang H, Shan L, Chen Z, Wang X, Huang D, Liu S, Chen X, Yang H, Hao D (2022) Exosomes derived from olfactory ensheathing cells provided neuroprotection for spinal cord injury by switching the phenotype of macrophages/microglia. Bioeng Transl Med 7:e10287. https://doi.org/10.1002/btm2.10287

    Article  CAS  PubMed  Google Scholar 

  91. Liddelow S, Barres B (2017) Reactive astrocytes: production, function, and therapeutic potential. Immunity 46:957–967. https://doi.org/10.1016/j.immuni.2017.06.006

    Article  CAS  PubMed  Google Scholar 

  92. Hale D, Ray S, Leung J, Holloway A, Chung R, West A, Chuah M (2011) Olfactory ensheathing cells moderate nuclear factor kappaB translocation in astrocytes. Mol Cell Neurosci 46:213–221. https://doi.org/10.1016/j.mcn.2010.09.004

    Article  CAS  PubMed  Google Scholar 

  93. Saglam A, Calof A, Wray S (2021) Novel factor in olfactory ensheathing cell-astrocyte crosstalk: anti-inflammatory protein α-crystallin B. Glia 69:1022–1036. https://doi.org/10.1002/glia.23946

    Article  CAS  PubMed  Google Scholar 

  94. Verdú E, García-Alías G, Forés J, Gudiño-Cabrera G, Muñetón V, Nieto-Sampedro M, Navarro X (2001) Effects of ensheathing cells transplanted into photochemically damaged spinal cord. NeuroReport 12:2303–2309. https://doi.org/10.1097/00001756-200108080-00005

    Article  PubMed  Google Scholar 

  95. Gorrie C, Hayward I, Cameron N, Kailainathan G, Nandapalan N, Sutharsan R, Wang J, Mackay-Sim A, Waite P (2010) Effects of human OEC-derived cell transplants in rodent spinal cord contusion injury. Brain Res 1337:8–20. https://doi.org/10.1016/j.brainres.2010.04.019

    Article  CAS  PubMed  Google Scholar 

  96. Ursavas S, Darici H, Karaoz E (2021) Olfactory ensheathing cells: unique glial cells promising for treatments of spinal cord injury. J Neurosci Res 99:1579–1597. https://doi.org/10.1002/jnr.24817

    Article  CAS  PubMed  Google Scholar 

  97. Li B, Xu C, Zhang J, Li Y, Duan Z (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 : MN 48:35–44. https://doi.org/10.1007/s12031-012-9740-6

    Article  CAS  PubMed  Google Scholar 

  98. Sasaki M, Hains B, Lankford K, Waxman S, Kocsis J (2006) Protection of corticospinal tract neurons after dorsal spinal cord transection and engraftment of olfactory ensheathing cells. Glia 53:352–359. https://doi.org/10.1002/glia.20285

    Article  PubMed  PubMed Central  Google Scholar 

  99. López-Vales R, García-Alías G, Forés J, Navarro X, Verdú E (2004) Increased expression of cyclo-oxygenase 2 and vascular endothelial growth factor in lesioned spinal cord by transplanted olfactory ensheathing cells. J Neurotrauma 21:1031–1043. https://doi.org/10.1089/0897715041651105

    Article  PubMed  Google Scholar 

  100. Yao R, Murtaza M, Velasquez J, Todorovic M, Rayfield A, Ekberg J, Barton M, St John J (2018) Olfactory ensheathing cells for spinal cord injury: sniffing out the issues. Cell Transplant 27:879–889. https://doi.org/10.1177/0963689718779353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Reshamwala R, Shah M, Belt L, Ekberg J, St John J (2020) Reliable cell purification and determination of cell purity: crucial aspects of olfactory ensheathing cell transplantation for spinal cord repair. Neural Regen Res 15:2016–2026. https://doi.org/10.4103/1673-5374.282218

    Article  PubMed  PubMed Central  Google Scholar 

  102. Wang X, Jiang C, Zhang Y, Chen Z, Wang Z, Yang H and Hao D (2021) Analysis and comparison of a spinal cord injury model with a single-axle-lever clip or a parallel-moving clip compression in rats. Spinal Cord.https://doi.org/10.1038/s41393-021-00720-7

Download references

Funding

This work was supported by the National Natural Science Foundation Item of China (No. 82071551 and 81830077) and Natural Science Foundation of Shaanxi Province (2020JM-686).

Author information

Authors and Affiliations

Authors

Contributions

HY conceived the review and supervised the project. CJ wrote the manuscript. CJ and YZJ contributed to literature review and editing. XHW contributed to literature review and drew the figures. ZC and YYZ contributed to the compiled table. DJH contributed to content and editing. All the authors contributed to the article and approved the submitted version.

Corresponding authors

Correspondence to Dingjun Hao or Hao Yang.

Ethics declarations

Ethics Approval and Consent to Participate

Not applicable.

Research Involving Human Participants and/or Animals

Not applicable.

Informed Consent

Not applicable.

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, C., Wang, X., Jiang, Y. et al. The Anti-inflammation Property of Olfactory Ensheathing Cells in Neural Regeneration After Spinal Cord Injury. Mol Neurobiol 59, 6447–6459 (2022). https://doi.org/10.1007/s12035-022-02983-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-022-02983-4

Keywords

Navigation