Skip to main content

Advertisement

SpringerLink
Log in

Failure of Schwann cells as supporting cells for adult neural progenitor cell grafts in the acutely injured spinal cord

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Adult neural progenitor cells (NPC) co-grafted with fibroblasts replace cystic lesion defects and promote cell-contact-mediated axonal regeneration in the acutely injured spinal cord. Fibroblasts are required as a platform to maintain NPC within the lesion; however, they are suspected to create an inhospitable milieu for regenerating central nervous system (CNS) axons. Therefore, we thought to replace fibroblasts by primary Schwann cells, which might serve as a superior scaffold to maintain NPC within the lesion and might further enhance axon regrowth and remyelination following spinal cord injury. Adult rats underwent a cervical dorsal column transection immediately followed by transplantation of either NPC/Schwann cell or NPC/Schwann cell/fibroblast co-grafts. Animals receiving Schwann cell or fibroblast grafts alone, or Schwann cell/fibroblast co-grafts served as controls. At 3 weeks after injury/transplantation, histological analysis revealed that only fibroblast-containing grafts were able to replace the cystic lesion defect. In both co-cultures and co-grafts, Schwann cells and NPC were segregated. Almost all NPC migrated out of the graft into the adjacent host spinal cord. As a consequence, only peripheral-type myelin, but no CNS-type myelin, was detected within co-grafts containing NPC/Schwann cells. Corticospinal axon regeneration into Schwann-cell-containing co-grafts was reduced. Taken together, Schwann cells within NPC grafts contribute to remyelination. However, Schwann cells fail as a supporting platform to maintain NPC within the graft and impair CNS axon regeneration; this makes them an unfavorable candidate to support/augment NPC grafts following spinal cord injury.

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

Similar content being viewed by others

References

  • Autilio-Gambetti L, Sipple J, Sudilovsky O, Gambetti P (1982) Intermediate filaments of Schwann cells. J Neurochem 38:774–780

    Article  PubMed  CAS  Google Scholar 

  • Bundesen LQ, Scheel TA, Bregman BS, Kromer LF (2003) Ephrin-B2 and EphB2 regulation of astrocyte-meningeal fibroblast interactions in response to spinal cord lesions in adult rats. J Neurosci 23:7789–7800

    PubMed  CAS  Google Scholar 

  • Bunge MB (1994) Transplantation of purified populations of Schwann cells into lesioned adult rat spinal cord. J Neurol 242:S36–S39

    Article  PubMed  CAS  Google Scholar 

  • Davies JE, Tang X, Denning JW, Archibald SJ, Davies SJ (2004) Decorin suppresses neurocan, brevican, phosphacan and NG2 expression and promotes axon growth across adult rat spinal cord injuries. Eur J Neurosci 19:1226–1242

    Article  PubMed  Google Scholar 

  • Dowsing BJ, Morrison WA, Nicola NA, Starkey GP, Bucci T, Kilpatrick TJ (1999) Leukemia inhibitory factor is an autocrine survival factor for Schwann cells. J Neurochem 73:96–104

    Article  PubMed  CAS  Google Scholar 

  • Ghirnikar RS, Eng LF (1994) Astrocyte-Schwann cell interactions in culture. Glia 11:367–377

    Article  PubMed  CAS  Google Scholar 

  • Griffin JW, Hoffman PN (1993) Degeneration and regeneration in the peripheral nervous system. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy. Saunders, Philadelphia, pp 361–376

    Google Scholar 

  • Honmou O, Felts PA, Waxman SG, Kocsis JD (1996) Restoration of normal conduction properties in demyelinated spinal cord axons in the adult rat by transplantation of exogenous Schwann cells. J Neurosci 16:3199–3208

    PubMed  CAS  Google Scholar 

  • Hughes SM, Lillien LE, Raff MC, Rohrer H, Sendtner M (1988) Ciliary neurotrophic factor induces type-2 astrocyte differentiation in culture. Nature 335:70–73

    Article  PubMed  CAS  Google Scholar 

  • Imaizumi T, Lankford KL, Kocsis JD (2000) Transplantation of olfactory ensheathing cells or Schwann cells restores rapid and secure conduction across the transected spinal cord. Brain Res 854:70–78

    Article  PubMed  CAS  Google Scholar 

  • Jessen KR, Morgan L, Brammer M, Mirsky R (1985) Galactocerebroside is expressed by non-myelin-forming Schwann cells in situ. J Cell Biol 101:1135–1143

    Article  PubMed  CAS  Google Scholar 

  • Keyvan-Fouladi N, Raisman G, Li Y (2005) Delayed repair of corticospinal tract lesions as an assay for the effectiveness of transplantation of Schwann cells. Glia 51:306–311

    Article  PubMed  Google Scholar 

  • Lakatos A, Franklin RJ, Barnett SC (2000) Olfactory ensheathing cells and Schwann cells differ in their in vitro interactions with astrocytes. Glia 32:214–225

    Article  PubMed  CAS  Google Scholar 

  • Lakatos A, Barnett SC, Franklin RJ (2003) Olfactory ensheathing cells induce less host astrocyte response and chondroitin sulphate proteoglycan expression than Schwann cells following transplantation into adult CNS white matter. Exp Neurol 184:237–246

    Article  PubMed  CAS  Google Scholar 

  • Lankford KL, Imaizumi T, Honmou O, Kocsis JD (2002) A quantitative morphometric analysis of rat spinal cord remyelination following transplantation of allogenic Schwann cells. J Comp Neurol 443:259–274

    Article  PubMed  Google Scholar 

  • Li Y, Raisman G (1994) Schwann cells induce sprouting in motor and sensory axons in the adult rat spinal cord. J Neurosci 14:4050–4063

    PubMed  CAS  Google Scholar 

  • Martin D, Robe P, Franzen R, Delree P, Schoenen J, Stevenaert A, Moonen G (1996) Effects of Schwann cell transplantation in a contusion model of rat spinal cord injury. J Neurosci Res 45:588–597

    Article  PubMed  CAS  Google Scholar 

  • Menei P, Montero-Menei C, Whittemore SR, Bunge RP, Bunge MB (1998) Schwann cells genetically modified to secrete human BDNF promote enhanced axonal regrowth across transected adult rat spinal cord. Eur J Neurosci 10:607–621

    Article  PubMed  CAS  Google Scholar 

  • Nakagaito Y, Yoshida T, Satoh M, Takeuchi M (1995) Effects of leukemia inhibitory factor on the differentiation of astrocyte progenitor cells from embryonic mouse cerebral hemispheres. Brain Res Dev Brain Res 87:220–223

    Article  PubMed  CAS  Google Scholar 

  • Pearse DD, Marcillo AE, Oudega M, Lynch MP, Wood PM, Bunge MB (2004) Transplantation of Schwann cells and olfactory ensheathing glia after spinal cord injury: does pretreatment with methylprednisolone and interleukin-10 enhance recovery? J Neurotrauma 21:1223–1239

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Plant GW, Bates ML, Bunge MB (2001) Inhibitory proteoglycan immunoreactivity is higher at the caudal than the rostral Schwann cell graft-transected spinal cord interface. Mol Cell Neurosci 17:471–487

    Article  PubMed  CAS  Google Scholar 

  • Richards LJ, Kilpatrick TJ, Dutton R, Tan SS, Gearing DP, Bartlett PF, Murphy M (1996) Leukaemia inhibitory factor or related factors promote the differentiation of neuronal and astrocytic precursors within the developing murine spinal cord. Eur J Neurosci 8:291–299

    Article  PubMed  CAS  Google Scholar 

  • Takami T, Oudega M, Bates ML, Wood PM, Kleitman N, Bunge MB (2002) Schwann cell but not olfactory ensheathing glia transplants improve hindlimb locomotor performance in the moderately contused adult rat thoracic spinal cord. J Neurosci 22:6670–6681

    PubMed  CAS  Google Scholar 

  • Tuszynski MH, Peterson DA, Ray J, Baird A, Nakahara Y, Gage FH (1994) Fibroblasts genetically modified to produce nerve growth factor induce robust neuritic ingrowth after grafting to the spinal cord. Exp Neurol 126:1–14

    Article  PubMed  CAS  Google Scholar 

  • Tuszynski MH, Weidner N, McCormack M, Miller I, Powell H, Conner J (1998) Grafts of genetically modified Schwann cells to the spinal cord: survival, axon growth, and myelination. Cell Transplant 7:187–196

    Article  PubMed  CAS  Google Scholar 

  • Vroemen M, Weidner N (2003) Purification of Schwann cells by selection of p75 low affinity nerve growth factor receptor expressing cells from adult peripheral nerve. J Neurosci Methods 124:135–143

    Article  PubMed  CAS  Google Scholar 

  • Vroemen M, Aigner L, Winkler J, Weidner N (2003) Adult neural progenitor cell grafts survive after acute spinal cord injury and integrate along axonal pathways. Eur J Neurosci 18:743–751

    Article  PubMed  Google Scholar 

  • Vroemen M, Weidner N, Blesch A (2005) Loss of gene expression in lentivirus- and retrovirus-transduced neural progenitor cells is correlated to migration and differentiation in the adult spinal cord. Exp Neurol 195:127–139

    Article  PubMed  CAS  Google Scholar 

  • Wang GY, Hirai K, Shimada H (1992) The role of laminin, a component of Schwann cell basal lamina, in rat sciatic nerve regeneration within antiserum-treated nerve grafts. Brain Res 570:116–125

    Article  PubMed  CAS  Google Scholar 

  • Weidner N, Blesch A, Grill RJ, Tuszynski MH (1999) Nerve growth factor-hypersecreting Schwann cell grafts augment and guide spinal cord axonal growth and remyelinate central nervous system axons in a phenotypically appropriate manner that correlates with expression of L1. J Comp Neurol 413:495–506

    Article  PubMed  CAS  Google Scholar 

  • Xu XM, Guenard V, Kleitman N, Bunge MB (1995) Axonal regeneration into Schwann cell-seeded guidance channels grafted into transected adult rat spinal cord. J Comp Neurol 351:145–160

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

We thank Dr. J. Archelos for the PO antibody.

Author information

Authors and Affiliations

  1. Department of Neurology, University of Regensburg, Universitätsstrasse 84, 93053, Regensburg, Germany

    Maurice Vroemen, Massimiliano Caioni, Ulrich Bogdahn & Norbert Weidner

Authors
  1. Maurice Vroemen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Massimiliano Caioni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ulrich Bogdahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Norbert Weidner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Norbert Weidner.

Additional information

This work was supported by the Institute International de Recherche en Paraplégie Geneva, on behalf of an anonymous donation, and ReForM-Program, University of Regensburg, School of Medicine.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vroemen, M., Caioni, M., Bogdahn, U. et al. 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 (2007). https://doi.org/10.1007/s00441-006-0252-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-006-0252-y

Keywords

Search

Navigation