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Experimental Cell Transplantation for Traumatic Spinal Cord Injury Regeneration: Intramedullar or Intrathecal Administration

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Stem Cells and Tissue Repair

Abstract

Animal experimentation models are a necessary prerequisite to human trials for the use of regenerative medicine in the treatment of spinal cord injuries. Considerable effort is required for the generation of a consistent and reproducible methodology to incur an injury and evaluate the results. The traumatic contusion model has been accepted as a model that closely mimics a typical human traumatic injury, and here we detail step by step an approach to generate a reproducible lesion in rats. Acute cell transplantation by intramedullar or intrathecal administration is described for regenerative interventions. The same model is suitable to design subacute or chronic therapeutic approaches by interventions 1 week or 1 month after lesion.

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References

  1. Goldschlager T, Oehme D, Ghosh P, Zannettino A, Rosenfeld JV, Jenkin G (2013) Current and future applications for stem cell therapies in spine surgery. Curr Stem Cell Res Ther 8:381

    Article  CAS  PubMed  Google Scholar 

  2. Keirstead HS, Nistor G, Bernal G, Totoiu M, Cloutier F, Sharp K, Steward O (2005) Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J Neurosci 25:4694

    Article  CAS  PubMed  Google Scholar 

  3. Tsuji O, Miura K, Okada Y, Fujiyoshi K, Mukaino M, Nagoshi N, Kitamura K, Kumagai G, Nishino M, Tomisato S, Higashi H, Nagai T, Katoh H, Kohda K, Matsuzaki Y, Yuzaki M, Ikeda E, Toyama Y, Nakamura M, Yamanaka S, Okano H (2010) Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury. Proc Natl Acad Sci U S A 107:12704

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Pearson H (2003) Spinal injuries: in search of a miracle. Nature 423:112

    Article  CAS  PubMed  Google Scholar 

  5. Erceg S, Ronaghi M, Oria M, Rosello MG, Arago MA, Lopez MG, Radojevic I, Moreno-Manzano V, Rodriguez-Jimenez FJ, Bhattacharya SS, Cordoba J, Stojkovic M (2010) Transplanted oligodendrocytes and motoneuron progenitors generated from human embryonic stem cells promote locomotor recovery after spinal cord transection. Stem Cells 28:1541

    Article  PubMed Central  PubMed  Google Scholar 

  6. Kerr CL, Letzen BS, Hill CM, Agrawal G, Thakor NV, Sterneckert JL, Gearhart JD, All AH (2010) Efficient differentiation of human embryonic stem cells into oligodendrocyte progenitors for application in a rat contusion model of spinal cord injury. Int J Neurosci 120:305

    Article  CAS  PubMed  Google Scholar 

  7. Kumagai G, Okada Y, Yamane J, Nagoshi N, Kitamura K, Mukaino M, Tsuji O, Fujiyoshi K, Katoh H, Okada S, Shibata S, Matsuzaki Y, Toh S, Toyama Y, Nakamura M, Okano H (2009) Roles of ES cell-derived gliogenic neural stem/progenitor cells in functional recovery after spinal cord injury. PLoS One 4:e7706

    Article  PubMed Central  PubMed  Google Scholar 

  8. Liang P, Jin LH, Liang T, Liu EZ, Zhao SG (2006) Human neural stem cells promote corticospinal axons regeneration and synapse reformation in injured spinal cord of rats. Chin Med J (Engl) 119:1331

    Google Scholar 

  9. Nori S, Okada Y, Yasuda A, Tsuji O, Takahashi Y, Kobayashi Y, Fujiyoshi K, Koike M, Uchiyama Y, Ikeda E, Toyama Y, Yamanaka S, Nakamura M, Okano H (2011) Grafted human-induced pluripotent stem-cell-derived neurospheres promote motor functional recovery after spinal cord injury in mice. Proc Natl Acad Sci U S A 108:16825

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Tsuji O, Miura K, Fujiyoshi K, Momoshima S, Nakamura M, Okano H (2011) Cell therapy for spinal cord injury by neural stem/progenitor cells derived from iPS/ES cells. Neurotherapeutics 8:668

    Article  PubMed Central  PubMed  Google Scholar 

  11. Varma AK, Das A, Wallace GT, Barry J, Vertegel AA, Ray SK, Banik NL (2013) Spinal cord injury: a review of current therapy, future treatments, and basic science frontiers. Neurochem Res 38:895

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Nishimura S, Yasuda A, Iwai H, Takano M, Kobayashi Y, Nori S, Tsuji O, Fujiyoshi K, Ebise H, Toyama Y, Okano H, Nakamura M (2013) Time-dependent changes in the microenvironment of injured spinal cord affects the therapeutic potential of neural stem cell transplantation for spinal cord injury. Mol Brain 6:3

    Article  PubMed Central  PubMed  Google Scholar 

  13. Cusimano M, Biziato D, Brambilla E, Donega M, Alfaro-Cervello C, Snider S, Salani G, Pucci F, Comi G, Garcia-Verdugo JM, De Palma M, Martino G, Pluchino S (2012) Transplanted neural stem/precursor cells instruct phagocytes and reduce secondary tissue damage in the injured spinal cord. Brain 135:447

    Article  PubMed Central  PubMed  Google Scholar 

  14. Moreno-Manzano V, Rodriguez-Jimenez FJ, Garcia-Rosello M, Lainez S, Erceg S, Calvo MT, Ronaghi M, Lloret M, Planells-Cases R, Sanchez-Puelles JM, Stojkovic M (2009) Activated spinal cord ependymal stem cells rescue neurological function. Stem Cells 27:733

    Article  PubMed  Google Scholar 

  15. Hodgetts SI, Simmons PJ, Plant GW (2013) A comparison of the behavioral and anatomical outcomes in sub-acute and chronic spinal cord injury models following treatment with human mesenchymal precursor cell transplantation and recombinant decorin. Exp Neurol 248C:343

    Article  Google Scholar 

  16. Yang CC, Shih YH, Ko MH, Hsu SY, Cheng H, Fu YS (2008) Transplantation of human umbilical mesenchymal stem cells from Wharton’s jelly after complete transection of the rat spinal cord. PLoS One 3:e3336

    Article  PubMed Central  PubMed  Google Scholar 

  17. Basso DM, Beattie MS, Bresnahan JC (1996) Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp Neurol 139:244

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by FISS PI13/00319, Instituto de Salud Carlos III (Cofinanciación FEDER), and the Spanish Consolider Ion Channel Initiative [CSD 2008-00005] MICINN grants.

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Correspondence to Victoria Moreno-Manzano .

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Alastrue-Agudo, A. et al. (2014). Experimental Cell Transplantation for Traumatic Spinal Cord Injury Regeneration: Intramedullar or Intrathecal Administration. In: Kioussi, C. (eds) Stem Cells and Tissue Repair. Methods in Molecular Biology, vol 1210. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1435-7_3

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  • DOI: https://doi.org/10.1007/978-1-4939-1435-7_3

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1434-0

  • Online ISBN: 978-1-4939-1435-7

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