Skip to main content

Advertisement

SpringerLink
Log in

Increased migration of olfactory ensheathing cells secreting the Nogo receptor ectodomain over inhibitory substrates and lesioned spinal cord

  • Research Article
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Olfactory ensheathing cell (OEC) transplantation emerged some years ago as a promising therapeutic strategy to repair injured spinal cord. However, inhibitory molecules are present for long periods of time in lesioned spinal cord, inhibiting both OEC migration and axonal regrowth. Two families of these molecules, chondroitin sulphate proteoglycans (CSPG) and myelin-derived inhibitors (MAIs), are able to trigger inhibitory responses in lesioned axons. Mounting evidence suggests that OEC migration is inhibited by myelin. Here we demonstrate that OEC migration is largely inhibited by CSPGs and that inhibition can be overcome by the bacterial enzyme Chondroitinase ABC. In parallel, we have generated a stable OEC cell line overexpressing the Nogo receptor (NgR) ectodomain to reduce MAI-associated inhibition in vitro and in vivo. Results indicate that engineered cells migrate longer distances than unmodified OECs over myelin or oligodendrocyte-myelin glycoprotein (OMgp)-coated substrates. In addition, they also show improved migration in lesioned spinal cord. Our results provide new insights toward the improvement of the mechanisms of action and optimization of OEC-based cell therapy for spinal cord lesion.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Abbreviations

CGN:

Cerebellar granule neurons

ChABC:

Chondroitinase ABC

CNS:

Central nervous system

CSPG:

Chondroitin sulphate proteoglycan

eGFP:

Enhanced green fluorescence protein

FTTM:

Fourier transform traction microscopy

GDNF:

Glial-derived neurotrophic factor

GFAP:

Glial fibrillary acidic protein

HRP:

Horseradish peroxidase

MAIs:

Myelin-derived molecules

NgR:

Nogo receptor

OEC:

Olfactory ensheathing cell

OMgp:

Oligodendrocyte-myelin glycoprotein

SCI:

Spinal cord injury

TFM:

Traction force microscopy

TUJ-1:

β3-Tubulin

References

  1. Dumont RJ, Okonkwo DO, Verma S, Hurlbert RJ, Boulos PT, Ellegala DB, Dumont AS (2001) Acute spinal cord injury, part I: pathophysiologic mechanisms. Clin Neuropharmacol 24(5):254–264

    Article  CAS  PubMed  Google Scholar 

  2. Furlan JC, Sakakibara BM, Miller WC, Krassioukov AV (2013) Global incidence and prevalence of traumatic spinal cord injury. Can J Neurol Sci 40(4):456–464 (H20571742RW34510)

    Article  PubMed  Google Scholar 

  3. Yang XF, Wang H, Wen L (2011) From myelin debris to inflammatory responses: a vicious circle in diffuse axonal injury. Med Hypotheses 77(1):60–62. doi:10.1016/j.mehy.2011.03.023

    Article  CAS  PubMed  Google Scholar 

  4. Yiu G, He Z (2006) Glial inhibition of CNS axon regeneration. Nat Rev Neurosci 7(8):617–627. doi:10.1038/nrn1956

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Llorens F, Gil V, del Rio JA (2011) Emerging functions of myelin-associated proteins during development, neuronal plasticity, and neurodegeneration. FASEB J 25(2):463–475. doi:10.1096/fj.10-162792

    Article  CAS  PubMed  Google Scholar 

  6. Wang H, Fang H, Dai J, Liu G, Xu ZJ (2013) Induced pluripotent stem cells for spinal cord injury therapy: current status and perspective. Neurol Sci 34(1):11–17. doi:10.1007/s10072-012-1145-3

    Article  PubMed  Google Scholar 

  7. Sun Y, Xu CC, Li J, Guan XY, Gao L, Ma LX, Li RX, Peng YW, Zhu GP (2013) Transplantation of oligodendrocyte precursor cells improves locomotion deficits in rats with spinal cord irradiation injury. PLoS One 8(2):e57534. doi:10.1371/journal.pone.0057534PONE-D-12-27814

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Li Y, Li D, Raisman G (2005) Interaction of olfactory ensheathing cells with astrocytes may be the key to repair of tract injuries in the spinal cord: the ‘pathway hypothesis’. J Neurocytol 34(3–5):343–351. doi:10.1007/s11068-005-8361-1

    Article  PubMed  Google Scholar 

  9. Roet KC, Verhaagen J (2014) Understanding the neural repair-promoting properties of olfactory ensheathing cells. Exp Neurol. doi:10.1016/j.expneurol.2014.05.007

    PubMed  Google Scholar 

  10. Raisman G, Barnett SC, Ramon-Cueto A (2012) Repair of central nervous system lesions by transplantation of olfactory ensheathing cells. Handb Clin Neurol 109:541–549. doi:10.1016/B978-0-444-52137-8.00033-4

    PubMed  Google Scholar 

  11. Doucette JR, Kiernan JA, Flumerfelt BA (1983) The re-innervation of olfactory glomeruli following transection of primary olfactory axons in the central or peripheral nervous system. J Anat 137(Pt 1):1–19

    PubMed Central  PubMed  Google Scholar 

  12. Nedelec S, Dubacq C, Trembleau A (2005) Morphological and molecular features of the mammalian olfactory sensory neuron axons: what makes these axons so special? J Neurocytol 34(1–2):49–64. doi:10.1007/s11068-005-5047-7

    Article  PubMed  Google Scholar 

  13. Ramon-Cueto A, Santos-Benito FF (2001) Cell therapy to repair injured spinal cords: olfactory ensheathing glia transplantation. Restor Neurol Neurosci 19(1–2):149–156

    CAS  PubMed  Google Scholar 

  14. Lu J, Feron F, Mackay-Sim A, Waite PM (2002) Olfactory ensheathing cells promote locomotor recovery after delayed transplantation into transected spinal cord. Brain 125(Pt 1):14–21

    Article  PubMed  Google Scholar 

  15. Lopez-Vales R, Fores J, Navarro X, Verdu E (2006) Olfactory ensheathing glia graft in combination with FK506 administration promote repair after spinal cord injury. Neurobiol Dis 24(3):443–454. doi:10.1016/j.nbd.2006.08.001

    Article  CAS  PubMed  Google Scholar 

  16. Ekberg JA, Amaya D, Mackay-Sim A, St John JA (2012) The migration of olfactory ensheathing cells during development and regeneration. Neuro-Signals 20(3):147–158. doi:10.1159/000330895

    Article  CAS  PubMed  Google Scholar 

  17. Ramon-Cueto A, Plant GW, Avila J, Bunge MB (1998) Long-distance axonal regeneration in the transected adult rat spinal cord is promoted by olfactory ensheathing glia transplants. J Neurosci 18(10):3803–3815

    CAS  PubMed  Google Scholar 

  18. 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(3):279–285. doi:10.1089/089771503321532860

    Article  PubMed  Google Scholar 

  19. 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(43):11120–11130. doi:10.1523/JNEUROSCI.3264-06.2006

    Article  CAS  PubMed  Google Scholar 

  20. Deng C, Gorrie C, Hayward I, Elston B, Venn M, Mackay-Sim A, Waite P (2006) Survival and migration of human and rat olfactory ensheathing cells in intact and injured spinal cord. J Neurosci Res 83(7):1201–1212. doi:10.1002/jnr.20817

    Article  CAS  PubMed  Google Scholar 

  21. Cao L, Su Z, Zhou Q, Lv B, Liu X, Jiao L, Li Z, Zhu Y, Huang Z, Huang A, He C (2006) Glial cell line-derived neurotrophic factor promotes olfactory ensheathing cells migration. Glia 54(6):536–544. doi:10.1002/glia.20403

    Article  PubMed  Google Scholar 

  22. Huang ZH, Wang Y, Su ZD, Geng JG, Chen YZ, Yuan XB, He C (2011) Slit-2 repels the migration of olfactory ensheathing cells by triggering Ca2+—dependent cofilin activation and RhoA inhibition. J Cell Sci 124(Pt 2):186–197. doi:10.1242/jcs.071357

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Wang Y, Huang ZH (2012) Morphological phenotypes of olfactory ensheathing cells display different migratory responses upon Slit-2. Exp Cell Res 318(15):1889–1900. doi:10.1016/j.yexcr.2012.05.024

    Article  CAS  PubMed  Google Scholar 

  24. Nocentini S, Reginensi D, Garcia S, Carulla P, Moreno-Flores MT, Wandosell F, Trepat X, Bribian A, del Rio JA (2012) Myelin-associated proteins block the migration of olfactory ensheathing cells: an in vitro study using single-cell tracking and traction force microscopy. Cell Mol Life Sci 69(10):1689–1703. doi:10.1007/s00018-011-0893-1

    Article  CAS  PubMed  Google Scholar 

  25. Su Z, Cao L, Zhu Y, Liu X, Huang Z, Huang A, He C (2007) Nogo enhances the adhesion of olfactory ensheathing cells and inhibits their migration. J Cell Sci 120(Pt 11):1877–1887. doi:10.1242/jcs.03448

    Article  CAS  PubMed  Google Scholar 

  26. 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(4):424–443. doi:10.1002/glia.20771

    Article  PubMed  Google Scholar 

  27. Riggio C, Nocentini S, Catalayud MP, Goya GF, Cuschieri A, Raffa V, Del Rio JA (2013) Generation of magnetized olfactory ensheathing cells for regenerative studies in the central and peripheral nervous tissue. Int J Mol Sci 14(6):10852–10868. doi:10.3390/ijms140610852

    Article  PubMed Central  PubMed  Google Scholar 

  28. Runyan SA, Phelps PE (2009) Mouse olfactory ensheathing glia enhance axon outgrowth on a myelin substrate in vitro. Exp Neurol 216(1):95–104. doi:10.1016/j.expneurol.2008.11.015

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Silver J, Miller JH (2004) Regeneration beyond the glial scar. Nat Rev Neurosci 5(2):146–156. doi:10.1038/nrn1326

    Article  CAS  PubMed  Google Scholar 

  30. Fawcett JW, Schwab ME, Montani L, Brazda N, Muller HW (2012) Defeating inhibition of regeneration by scar and myelin components. Handb Clin Neurol 109:503–522. doi:10.1016/B978-0-444-52137-8.00031-0

    PubMed  Google Scholar 

  31. Cregg JM, DePaul MA, Filous AR, Lang BT, Tran A, Silver J (2014) Functional regeneration beyond the glial scar. Exp Neurol 253:197–207. doi:10.1016/j.expneurol.2013.12.024

    Article  PubMed  Google Scholar 

  32. Fouad K, Schnell L, Bunge MB, Schwab ME, Liebscher T, Pearse DD (2005) Combining Schwann cell bridges and olfactory-ensheathing glia grafts with chondroitinase promotes locomotor recovery after complete transection of the spinal cord. J Neurosci 25(5):1169–1178. doi:10.1523/JNEUROSCI.3562-04.2005

    Article  CAS  PubMed  Google Scholar 

  33. Fouad K, Pearse DD, Tetzlaff W, Vavrek R (2009) Transplantation and repair: combined cell implantation and chondroitinase delivery prevents deterioration of bladder function in rats with complete spinal cord injury. Spinal Cord 47(10):727–732. doi:10.1038/sc.2009.10

    Article  CAS  PubMed  Google Scholar 

  34. Del Rio JA, Soriano E (2007) Overcoming chondroitin sulphate proteoglycan inhibition of axon growth in the injured brain: lessons from chondroitinase ABC. Curr Pharm Des 13(24):2485–2492

    Article  PubMed  Google Scholar 

  35. Moreno-Flores MT, Lim F, Martin-Bermejo MJ, Diaz-Nido J, Avila J, Wandosell F (2003) Immortalized olfactory ensheathing glia promote axonal regeneration of rat retinal ganglion neurons. J Neurochem 85(4):861–871

    Article  CAS  PubMed  Google Scholar 

  36. Fournier AE, Gould GC, Liu BP, Strittmatter SM (2002) Truncated soluble Nogo receptor binds Nogo-66 and blocks inhibition of axon growth by myelin. J Neurosci 22(20):8876–8883 (22/20/8876)

    CAS  PubMed  Google Scholar 

  37. He XL, Bazan JF, McDermott G, Park JB, Wang K, Tessier-Lavigne M, He Z, Garcia KC (2003) Structure of the Nogo receptor ectodomain: a recognition module implicated in myelin inhibition. Neuron 38(2):177–185 (S0896627303002320)

    Article  CAS  PubMed  Google Scholar 

  38. Li S, Liu BP, Budel S, Li M, Ji B, Walus L, Li W, Jirik A, Rabacchi S, Choi E, Worley D, Sah DW, Pepinsky B, Lee D, Relton J, Strittmatter SM (2004) Blockade of Nogo-66, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein by soluble Nogo-66 receptor promotes axonal sprouting and recovery after spinal injury. J Neurosci 24(46):10511–10520. doi:10.1523/JNEUROSCI.2828-04.2004

    Article  CAS  PubMed  Google Scholar 

  39. Wang X, Baughman KW, Basso DM, Strittmatter SM (2006) Delayed Nogo receptor therapy improves recovery from spinal cord contusion. Ann Neurol 60(5):540–549. doi:10.1002/ana.20953

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Seira O, Gavin R, Gil V, Llorens F, Rangel A, Soriano E, del Rio JA (2010) Neurites regrowth of cortical neurons by GSK3beta inhibition independently of Nogo receptor 1. J Neurochem 113(6):1644–1658. doi:10.1111/j.1471-4159.2010.06726.x

    CAS  PubMed  Google Scholar 

  41. Mingorance A, Fontana X, Sole M, Burgaya F, Urena JM, Teng FY, Tang BL, Hunt D, Anderson PN, Bethea JR, Schwab ME, Soriano E, del Rio JA (2004) Regulation of Nogo and Nogo receptor during the development of the entorhino-hippocampal pathway and after adult hippocampal lesions. Mol Cell Neurosci 26(1):34–49. doi:10.1016/j.mcn.2004.01.001

    Article  CAS  PubMed  Google Scholar 

  42. Montolio M, Messeguer J, Masip I, Guijarro P, Gavin R, Antonio Del Rio J, Messeguer A, Soriano E (2009) A semaphorin 3A inhibitor blocks axonal chemorepulsion and enhances axon regeneration. Chem Biol 16(7):691–701. doi:10.1016/j.chembiol.2009.05.006

    Article  CAS  PubMed  Google Scholar 

  43. Niederost B, Oertle T, Fritsche J, McKinney RA, Bandtlow CE (2002) Nogo-A and myelin-associated glycoprotein mediate neurite growth inhibition by antagonistic regulation of RhoA and Rac1. J Neurosci 22(23):10368–10376

    CAS  PubMed  Google Scholar 

  44. Taylor AM, Blurton-Jones M, Rhee SW, Cribbs DH, Cotman CW, Jeon NL (2005) A microfluidic culture platform for CNS axonal injury, regeneration and transport. Nat Methods 2(8):599–605. doi:10.1038/nmeth777

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Butler JP, Tolic-Norrelykke IM, Fabry B, Fredberg JJ (2002) Traction fields, moments, and strain energy that cells exert on their surroundings. Am J Physiol Cell Physiol 282(3):C595–C605. doi:10.1152/ajpcell.00270.2001

    Article  CAS  PubMed  Google Scholar 

  46. Trepat X, Wasserman MR, Angelini TE, Millet E, Weitz DA, Butler JP, Fredberg JJ (2009) Physical forces during collective cell migration. Nat Phys 5 (6):426–430. doi:http://www.nature.com/nphys/journal/v5/n6/suppinfo/nphys1269_S1.html

  47. 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(16):1708–1719. doi:10.1002/glia.20586

    Article  PubMed  Google Scholar 

  48. 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(10):1735–1750. doi:10.1007/s00018-010-0280-3

    Article  CAS  PubMed  Google Scholar 

  49. Roca-Cusachs P, Sunyer R, Trepat X (2013) Mechanical guidance of cell migration: lessons from chemotaxis. Curr Opin Cell Biol 25(5):543–549. doi:10.1016/j.ceb.2013.04.010

    Article  CAS  PubMed  Google Scholar 

  50. Trepat X, Chen Z, Jacobson K (2012) Cell migration. Comprehensive. Physiology 2(4):2369–2392. doi:10.1002/cphy.c110012

    Google Scholar 

  51. Tambe DT, Croutelle U, Trepat X, Park CY, Kim JH, Millet E, Butler JP, Fredberg JJ (2013) Monolayer stress microscopy: limitations, artifacts, and accuracy of recovered intercellular stresses. PLoS One 8(2):e55172. doi:10.1371/journal.pone.0055172

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. McKeon RJ, Hoke A, Silver J (1995) Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars. Exp Neurol 136(1):32–43. doi:10.1006/exnr.1995.1081

    Article  CAS  PubMed  Google Scholar 

  53. Mountney A, Zahner MR, Sturgill ER, Riley CJ, Aston JW, Oudega M, Schramm LP, Hurtado A, Schnaar RL (2013) Sialidase, chondroitinase ABC, and combination therapy after spinal cord contusion injury. J Neurotrauma 30(3):181–190. doi:10.1089/neu.2012.2353

    Article  PubMed Central  PubMed  Google Scholar 

  54. Bradbury EJ, Moon LD, Popat RJ, King VR, Bennett GS, Patel PN, Fawcett JW, McMahon SB (2002) Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 416(6881):636–640. doi:10.1038/416636a

    Article  CAS  PubMed  Google Scholar 

  55. Bradbury EJ, Carter LM (2011) Manipulating the glial scar: chondroitinase ABC as a therapy for spinal cord injury. Brain Res Bull 84(4–5):306–316. doi:10.1016/j.brainresbull.2010.06.015

    Article  CAS  PubMed  Google Scholar 

  56. Zhang C, He X, Lan B, Li H (2009) Study on repair of subacute spinal cord injury by transplantation of olfactory ensheathing cells combined with chondroitinase ABC in adult rats. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 23(1):8–13

    PubMed  Google Scholar 

  57. Kanno H, Pressman Y, Moody A, Berg R, Muir EM, Rogers JH, Ozawa H, Itoi E, Pearse DD, Bunge MB (2014) Combination of engineered Schwann cell grafts to secrete neurotrophin and chondroitinase promotes axonal regeneration and locomotion after spinal cord injury. J Neurosci 34(5):1838–1855. doi:10.1523/JNEUROSCI.2661-13.2014

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Cafferty WB, Yang SH, Duffy PJ, Li S, Strittmatter SM (2007) Functional axonal regeneration through astrocytic scar genetically modified to digest chondroitin sulfate proteoglycans. J Neurosci 27(9):2176–2185. doi:10.1523/JNEUROSCI.5176-06.2007

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. 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(10):2241–2253. doi:10.1007/s00018-003-3265-7

    Article  CAS  PubMed  Google Scholar 

  60. Park JW, Kim HJ, Kang MW, Jeon NL (2013) Advances in microfluidics-based experimental methods for neuroscience research. Lab Chip 13(4):509–521. doi:10.1039/c2lc41081h

    Article  CAS  PubMed  Google Scholar 

  61. Taylor AM, Rhee SW, Tu CH, Cribbs DH, Cotman CW, Jeon NL (2003) Microfluidic multicompartment device for neuroscience research. Langmuir 19(5):1551–1556. doi:10.1021/la026417v

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Fournier MF, Sauser R, Ambrosi D, Meister JJ, Verkhovsky AB (2010) Force transmission in migrating cells. J Cell Biol 188(2):287–297. doi:10.1083/jcb.200906139

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  63. Mierke CT, Rosel D, Fabry B, Brabek J (2008) Contractile forces in tumor cell migration. Eur J Cell Biol 87(8–9):669–676. doi:10.1016/j.ejcb.2008.01.002

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Wang HB, Dembo M, Hanks SK, Wang Y (2001) Focal adhesion kinase is involved in mechanosensing during fibroblast migration. Proc Natl Acad Sci USA 98(20):11295–11300. doi:10.1073/pnas.20120119898/20/11295

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Li S, Guan JL, Chien S (2005) Biochemistry and biomechanics of cell motility. Annu Rev Biomed Eng 7:105–150. doi:10.1146/annurev.bioeng.7.060804.100340

    Article  CAS  PubMed  Google Scholar 

  66. Schwab ME (2010) Functions of Nogo proteins and their receptors in the nervous system. Nat Rev Neurosci 11(12):799–811. doi:10.1038/nrn2936

    Article  CAS  PubMed  Google Scholar 

  67. Hsieh SH, Ferraro GB, Fournier AE (2006) Myelin-associated inhibitors regulate cofilin phosphorylation and neuronal inhibition through LIM kinase and Slingshot phosphatase. J Neurosci 26(3):1006–1015. doi:10.1523/JNEUROSCI.2806-05.2006

    Article  CAS  PubMed  Google Scholar 

  68. Mimura F, Yamagishi S, Arimura N, Fujitani M, Kubo T, Kaibuchi K, Yamashita T (2006) Myelin-associated glycoprotein inhibits microtubule assembly by a Rho-kinase-dependent mechanism. J Biol Chem 281(23):15970–15979. doi:10.1074/jbc.M510934200

    Article  CAS  PubMed  Google Scholar 

  69. 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. doi:10.1186/1471-2202-14-141

    Article  PubMed Central  PubMed  Google Scholar 

  70. Ould-Yahoui A, Sbai O, Baranger K, Bernard A, Gueye Y, Charrat E, Clement B, Gigmes D, Dive V, Girard SD, Feron F, Khrestchatisky M, Rivera S (2013) Role of matrix metalloproteinases in migration and neurotrophic properties of nasal olfactory stem and ensheathing cells. Cell Transplant 22(6):993–1010. doi:10.3727/096368912X657468

    Article  PubMed  Google Scholar 

  71. Dickendesher TL, Baldwin KT, Mironova YA, Koriyama Y, Raiker SJ, Askew KL, Wood A, Geoffroy CG, Zheng B, Liepmann CD, Katagiri Y, Benowitz LI, Geller HM, Giger RJ (2012) NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans. Nat Neurosci 15(5):703–712. doi:10.1038/nn.3070

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Lukovic D, Valdes-Sanchez L, Sanchez-Vera I, Moreno-Manzano V, Stojkovic M, Bhattacharya SS, Erceg S (2014) Brief report: astrogliosis promotes functional recovery of completely transected spinal cord following transplantation of hESC-derived oligodendrocyte and motoneuron progenitors. Stem Cells 32(2):594–599. doi:10.1002/stem.1562

    Article  CAS  PubMed  Google Scholar 

  73. Vukovic J, Marmorstein LY, McLaughlin PJ, Sasaki T, Plant GW, Harvey AR, Ruitenberg MJ (2009) Lack of fibulin-3 alters regenerative tissue responses in the primary olfactory pathway. Matrix Biol 28(7):406–415. doi:10.1016/j.matbio.2009.06.001

    Article  CAS  PubMed  Google Scholar 

  74. Schwarting GA, Kostek C, Ahmad N, Dibble C, Pays L, Puschel AW (2000) Semaphorin 3A is required for guidance of olfactory axons in mice. J Neurosci 20(20):7691–7697

    CAS  PubMed  Google Scholar 

  75. Lee JK, Geoffroy CG, Chan AF, Tolentino KE, Crawford MJ, Leal MA, Kang B, Zheng B (2010) Assessing spinal axon regeneration and sprouting in Nogo-, MAG-, and OMgp-deficient mice. Neuron 66(5):663–670. doi:10.1016/j.neuron.2010.05.002

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. Masliah E, Xie F, Dayan S, Rockenstein E, Mante M, Adame A, Patrick CM, Chan AF, Zheng B (2010) Genetic deletion of Nogo/Rtn4 ameliorates behavioral and neuropathological outcomes in amyloid precursor protein transgenic mice. Neuroscience 169(1):488–494. doi:10.1016/j.neuroscience.2010.04.045

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. Winzeler AM, Mandemakers WJ, Sun MZ, Stafford M, Phillips CT, Barres BA (2011) The lipid sulfatide is a novel myelin-associated inhibitor of CNS axon outgrowth. J Neurosci 31(17):6481–6492. doi:10.1523/JNEUROSCI.3004-10201131/17/6481 pii

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  78. Stiles TL, Dickendesher TL, Gaultier A, Fernandez-Castaneda A, Mantuano E, Giger RJ, Gonias SL (2013) LDL receptor-related protein-1 is a sialic-acid-independent receptor for myelin-associated glycoprotein that functions in neurite outgrowth inhibition by MAG and CNS myelin. J Cell Sci 126(Pt 1):209–220. doi:10.1242/jcs.113191

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  79. Huang ZH, Wang Y, Cao L, Su ZD, Zhu YL, Chen YZ, Yuan XB, He C (2008) Migratory properties of cultured olfactory ensheathing cells by single-cell migration assay. Cell Res 18(4):479–490. doi:10.1038/cr.2008.38

    Article  CAS  PubMed  Google Scholar 

  80. Fan Z, Shen Y, Zhang F, Zuo B, Lu Q, Wu P, Xie Z, Dong Q, Zhang H (2013) Control of olfactory ensheathing cell behaviors by electrospun silk fibroin fibers. Cell Transplant 22(Suppl 1):S39–S50. doi:10.3727/096368913X672190

    Article  PubMed  Google Scholar 

  81. Zhang LL, Huang LH, Zhang ZX, Hao DJ, He BR (2013) Compatibility of olfactory ensheathing cells with functionalized self-assembling peptide scaffold in vitro. Chin Med J (Engl) 126(20):3891–3896

    CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Tom Yohannan for editorial advice and Oscar Castaño, Miguel Ángel Mateos-Timoneda and E. Engel for helping in S.E.M studies and offering comments on the manuscript. We also thank M. Segura and M. Morell for technical assistance, and members of the Del Río, Samitier and Trepat laboratories for stimulating discussions and ideas. This research was supported by the Spanish Ministry of Science and Innovation (BFU2012-32617), the Generalitat de Catalunya (SGR2014-1218), La Caixa Obra Social Foundation, and the Basque Foundation of Health and Innovation Research (BIO12/AL/004) to JADR. RG was supported by Fondo de Investigaciones Sanitarias (PI11-00075) and work in FW’s lab was supported by grants from the Dirección General de Ciencia y Tecnologia-DGCYT-(SAF2012-39148-C03-01), and EU-FP7-2009-(CT222887), as well as an institutional grant from the ‘Fundación Areces’. Work at XN’s lab was supported by grants from the Spanish Ministry of Science and Innovation (SAF2009-12495), and funds from CIBERNED and Cell Therapy Network (TERCEL) of the Instituto de Salud Carlos III of Spain. XT was supported by the Spanish Ministry of Economy and Competitiveness (BFU2012-38146) and the European Research Council (Grant Agreement 242993). JS was supported by the Fundación Botín and Institute Salud Carlos III PI10/01171. PC was supported by AGAUR, and SN and OS were supported by MINECO and IBEC. DR was supported by a fellowship from the National Commission for Science and Technology (CONICYT, Chile) and A. M-A was supported by a fellowship from the Fundación Tatiana Pérez de Guzmán el Bueno.

Author information

Authors and Affiliations

  1. Molecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia (IBEC), Parc Científic de Barcelona, Baldiri Reixac 15-12, 08028, Barcelona, Spain

    Diego Reginensi, Patricia Carulla, Sara Nocentini, Oscar Seira, Andreu Matamoros-Angles, Rosalina Gavín & José Antonio del Río

  2. Department of Cell Biology, Universitat de Barcelona, Barcelona, Spain

    Diego Reginensi, Patricia Carulla, Sara Nocentini, Oscar Seira, Andreu Matamoros-Angles, Rosalina Gavín & José Antonio del Río

  3. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain

    Diego Reginensi, Patricia Carulla, Sara Nocentini, Oscar Seira, Andreu Matamoros-Angles, Rosalina Gavín & José Antonio del Río

  4. Blusson Spinal Cord Centre and Department of Zoology, Faculty of Science, International Collaboration On Repair Discoveries (ICORD), University of British Columbia, Vancouver, Canada

    Oscar Seira

  5. Integrative cell and tissue dynamics, Institute for Bioengineering of Catalonia, 08028, Barcelona, Spain

    Xavier Serra-Picamal

  6. Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Edif. M, Universitat Autònoma de Barcelona, Bellaterra, 08193, Spain

    Abel Torres-Espín & Xavier Navarro

  7. Grupo de Neurobiología, Instituto de Investigaciones Biosanitarias, Facultad de Ciencias Biosanitarias, Universidad Francisco de Vitoria, Pozuelo de Alarcón 28223, Madrid, Spain

    Abel Torres-Espín & Xavier Navarro

  8. Centro de Biología Molecular ‘Severo Ochoa’, Universidad Autónoma de Madrid (CBM-UAM), Madrid, Spain

    María Teresa Moreno-Flores

  9. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), CBM-UAM, Madrid, Spain

    Francisco Wandosell

  10. Nanobioengineering Laboratory, . Institute for Bioengineering of Catalonia, 08028, Barcelona, Spain

    Josep Samitier

  11. Department of Electronics, University of Barcelona, Centro de Investigaciòn Médica en Red, Biomecánica, Biomateriales y Nanotecnologìa (CIBERBBN), Barcelona, Spain

    Josep Samitier

  12. University of Barcelona, 08028, Barcelona, Spain

    Xavier Trepat

  13. Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010, Barcelona, Spain

    Xavier Trepat

Authors
  1. Diego Reginensi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patricia Carulla
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sara Nocentini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Oscar Seira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xavier Serra-Picamal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Abel Torres-Espín
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Andreu Matamoros-Angles
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rosalina Gavín
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. María Teresa Moreno-Flores
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Francisco Wandosell
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Josep Samitier
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Xavier Trepat
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Xavier Navarro
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. José Antonio del Río
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to José Antonio del Río.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (JPEG 1537 kb)

Supplementary material 2 (JPEG 2406 kb)

Supplementary material 3 (MOV 12887 kb)

Supplementary material 4 (MOV 3030 kb)

Supplementary material 5 (MOV 4809 kb)

Supplementary material 6 (MOV 2043 kb)

Supplementary material 7 (MOV 4769 kb)

Supplementary material 8 (MOV 5708 kb)

Supplementary material 9 (MOV 5874 kb)

Supplementary material 10 (MOV 3618 kb)

Supplementary material 11 (MOV 3812 kb)

Supplementary material 12 (MOV 4506 kb)

Supplementary material 13 (MOV 5178 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Reginensi, D., Carulla, P., Nocentini, S. et al. Increased migration of olfactory ensheathing cells secreting the Nogo receptor ectodomain over inhibitory substrates and lesioned spinal cord. Cell. Mol. Life Sci. 72, 2719–2737 (2015). https://doi.org/10.1007/s00018-015-1869-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-015-1869-3

Keywords

Search

Navigation