Skip to main content

Advertisement

SpringerLink
Log in

A Review of Neural Stem Cell Transplant Therapy for Traumatic Spinal Cord Injury

  • Medicine
  • Published:
SN Comprehensive Clinical Medicine Aims and scope Submit manuscript

Abstract

Stem cell transplants, and neural stem cells (NSCs) in particular, hold tremendous potential in recreating axonal relays that bridge traumatic spinal cord injuries (SCIs). While currently there is no standardized transplant methodology, common themes emerge from reviewing recent studies. Current research focuses on injecting NSCs without damaging existing tissue, overcoming common hurdles such as glial scarring, immune reaction, and tumorigenesis and inducing proper differentiation into sensory and motor neurons. Notably, scaffolding holds promise in improving outcomes. Although animal trials have demonstrated NSC ability to improve motor function, human trials are mostly limited to verification of safety instead of efficacy. While controversy and debate surround the use of stem cells, NSCs for SCI merit further exploration.

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

Similar content being viewed by others

Data availability

Not Applicable

References

  1. National Spinal Cord Injury Statistical Center, Facts and figures at a glance https://www.nscisc.uab.edu/Public/Facts%20and%20Figures%20-%202018.pdf Accessed 28 April 2020

  2. Lim S, Shiue Y, Ho C, Yu S, Kao P, Wang J, et al. Anxiety and depression in patients with traumatic spinal cord injury: a nationwide population-based cohort study. PLoS ONE. 2017;12(1):e0169623.

    Article  Google Scholar 

  3. Lu P, Graham L, Wang Y, Wu D, Tuszynski M. Promotion of survival and differentiation of neural stem cells with fibrin and growth factor cocktails after severe spinal cord injury. J Vis Exp. 2014;89:e50641.

    Google Scholar 

  4. Burns A, Marino R, Kalsi-Ryan S, Middleton J, Tetreault L, Dettori J, et al. Type and timing of rehabilitation following acute and subacute spinal cord injury: a systematic review. Global Spine J. 2017;7(3_suppl):175S–94S.

    Article  Google Scholar 

  5. Siddall PJ, Molloy AR, Walker S, Mather LE, Rutkowski SB, Cousins MJ. The efficacy of intrathecal morphine and clonidine in the treatment of pain after spinal cord injury. Anesth Analg. 2000;91:1493–8.

    Article  CAS  Google Scholar 

  6. Saval A, Chiodo AE. Intrathecal baclofen for spasticity management: a comparative analysis of spasticity of spinal vs cortical origin. J Spinal Cord Med. 2010;33:16–21.

    Article  Google Scholar 

  7. Curtis E, Martin JR, Gabel B, Sidhu N, Rzesiewicz TK, Mandeville R, et al. A first-in-human, phase I study of neural stem cell transplantation for chronic spinal cord injury. Cell Stem Cell. 2018;22:941–950.e6.

    Article  CAS  Google Scholar 

  8. Kim SH, Oh K, Jin HK, Bae J. Immune inflammatory modulation as a potential therapeutic strategy of stem cell therapy for ALS and neurodegenerative diseases. BMB Rep. 2018;51:545–6.

    Article  CAS  Google Scholar 

  9. Shao A, Tu S, Lu J, Zhang J. Crosstalk between stem cell and spinal cord injury: pathophysiology and treatment strategies. Stem Cell Res Ther. 2019;10:238. https://doi.org/10.1186/s13287-019-1357-z.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Shimada I, LeComte M, Granger J, Quinlan N, Spees J. Self-renewal and differentiation of reactive astrocyte-derived neural stem/progenitor cells isolated from the cortical peri-infarct area after stroke. J Neurosci. 2012;32(23):7926–40.

    Article  CAS  Google Scholar 

  11. Nishimura S, Yasuda A, Iwai H, Takano M, Kobayashi Y, Nori S, et al. Time-dependent changes in the microenvironment of injured spinal cord affects the therapeutic potential of neural stem cell transplantation for spinal cord injury. Molec Brain. 2013;6:3. https://doi.org/10.1186/1756-6606-6-3.

    Article  Google Scholar 

  12. Suzuki H, Ahuja CS, Salewski RP, Li L, Satkunendrarajah K, Nagoshi N, et al. Neural stem cell mediated recovery is enhanced by chondroitinase ABC pretreatment in chronic cervical spinal cord injury. PLoS One. 2017;12:e0182339. https://doi.org/10.1371/journal.pone.0182339.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Levi AD, Okonkwo DO, Park P, Jenkins AL, Kurpad SN, Parr AM, et al. Emerging safety of intramedullary transplantation of human neural stem cells in chronic cervical and thoracic spinal cord injury. Neurosurgery. 2018;82:562–75.

    Article  Google Scholar 

  14. Lima C, Pratas-Vital J, Escada P, Hasse-Ferreira A, Capucho C, Peduzzi JD. Olfactory mucosa autografts in human spinal cord injury: a pilot clinical study. J Spinal Cord Med. 2006;29:191–203. https://doi.org/10.1080/10790268.2006.11753874.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Shin JC, Kim KN, Yoo J, Kim I, Yun S, Lee H, et al. Clinical trial of human fetal brain-derived neural stem/progenitor cell transplantation in patients with traumatic cervical spinal cord injury. Neural Plast. 2015;2015:630932.

    Article  Google Scholar 

  16. Lima C, Escada P, Pratas-Vital J, Branco C, Arcangeli CA, Lazzeri G, et al. Olfactory mucosal autografts and rehabilitation for chronic traumatic spinal cord injury. Neurorehabil Neural Repair. 2010;24:10–22.

    Article  Google Scholar 

  17. Nori S, Okada Y, Yasuda A, Tsuji O, Takahashi Y, Kobayashi Y, et al. 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. 2011;108:16825–30. https://doi.org/10.1073/pnas.1108077108.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Fujimoto Y, Abematsu M, Falk A, Tsujimura K, Sanosaka T, Juliandi B, et al. Treatment of a mouse model of spinal cord injury by transplantation of human induced pluripotent stem cell-derived long-term self-renewing neuroepithelial-like stem cells. Stem Cells. 2012;30:1163–73. https://doi.org/10.1002/stem.1083.

    Article  CAS  PubMed  Google Scholar 

  19. Amemori T, Ruzicka J, Romanyuk N, Jhanwar-Uniyal M, Sykova E, Jendelova P. Comparison of intraspinal and intrathecal implantation of induced pluripotent stem cell-derived neural precursors for the treatment of spinal cord injury in rats. Stem Cell Res Ther. 2015;6:257. https://doi.org/10.1186/s13287-015-0255-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Robinson J, Lu P. Optimization of trophic support for neural stem cell grafts in sites of spinal cord injury. Exp Neurol. 2017;291:87–97. https://doi.org/10.1016/j.expneurol.2017.02.007.

    Article  CAS  PubMed  Google Scholar 

  21. Xu B, Zhao Y, Xiao Z, Wang B, Liang H, Li X, et al. A dual functional scaffold tethered with EGFR antibody promotes neural stem cell retention and neuronal differentiation for spinal cord injury repair. Adv Healthc Mater. 2017;6:1601279. https://doi.org/10.1002/adhm.201601279.

    Article  CAS  Google Scholar 

  22. Zweckberger K, Ahuja CS, Liu Y, Wang J, Fehlings MG. Self-assembling peptides optimize the post-traumatic milieu and synergistically enhance the effects of neural stem cell therapy after cervical spinal cord injury. Acta Biomater. 2016;42:77–89. https://doi.org/10.1016/j.actbio.2016.06.016.

    Article  CAS  PubMed  Google Scholar 

  23. Yousefifard M, Rahimi-Movaghar V, Nasirinezhad F, Baikpour M, Safari S, Saadat S, et al. Neural stem/progenitor cell transplantation for spinal cord injury treatment; a systematic review and meta-analysis. Neuroscience. 2016;322:377–97. https://doi.org/10.1016/j.neuroscience.2016.02.034.

    Article  CAS  PubMed  Google Scholar 

  24. Kadoya K, Lu P, Nguyen K, Lee-Kubli C, Kumamaru H, Yao L, et al. Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration. Nat.Med. 2016;22:479–87. https://doi.org/10.1038/nm.4066.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lee SH, Chung YN, Kim YH, Kim YJ, Park JP, Kwon DK, et al. Effects of human neural stem cell transplantation in canine spinal cord hemisection. Neurol.Res. 2009;31:996–1002. https://doi.org/10.1179/174313209X385626.

    Article  PubMed  Google Scholar 

  26. Rosenzweig ES, Brock JH, Lu P, Kumamaru H, Salegio EA, Kadoya K, et al. Restorative effects of human neural stem cell grafts on the primate spinal cord. Nat.Med. 2018;24:484–90. https://doi.org/10.1038/nm.4502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Levi AD, Anderson KD, Okonkwo DO, Park P, Bryce TN, Kurpad SN, et al. Clinical outcomes from a multi-center study of human neural stem cell transplantation in chronic cervical spinal cord injury. J Neurotrauma. 2019;36:891–902.

    Article  Google Scholar 

  28. Pope Benedict XVI. ADDRESS OF HIS HOLINESS POPE BENEDICT XVI TO PARTICIPANTS OF THE SYMPOSIUM ON THE THEME: STEM CELLS: WHAT FUTURE FOR THERAPY? SCIENTIFIC ASPECTS AND BIOETHICAL PROBLEMS. Cell Prolif. 2008;41:4–6. https://doi.org/10.1111/j.1365-2184.2008.00511.x.

    Article  PubMed  Google Scholar 

  29. Turner L. The US direct-to-consumer marketplace for autologous stem cell interventions. Perspect Biol Med. 2018;61:7–24. https://doi.org/10.1353/pbm.2018.0024.

    Article  PubMed  Google Scholar 

  30. Riva L, Campanozzi L, Vitali M, Ricci G, Tambone V. Unproven stem cell therapies: is it my right to try? Annali Dell'Istituto Superiore Di Sanita. 2019;55:179–85. https://doi.org/10.4415/ANN_19_02_10.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Dr. Ian Gallicano for guidance on the topic of this literature review, the Special Master’s Program at Georgetown University for the opportunity to write this review, and the anonymous readers who offered critique of our early drafts.

Code Availability

Not Applicable

Author information

Authors and Affiliations

  1. Special Master’s in Physiology, Georgetown University, 3900 Reservoir Rd. NW, Washington, D. C., 20007, USA

    Eric Fu, Katherine Grayden & Madeline Kaplan

  2. Irvine, USA

    Eric Fu

  3. Georgetown University School of Medicine, Georgetown University Medical Center, 3900 Reservoir Rd. NW, 2007, Washington D.C, USA

    Kyle Wallace

Authors
  1. Eric Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kyle Wallace
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katherine Grayden
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Madeline Kaplan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

“Introduction” and “Studies Involving Non-Human Models” written by Katie Grayden. “Mechanisms” written by Eric Fu. “Studies Involving Human Models” written by Kyle Wallace. “Controversies” and “Conclusion” written by Madeline Kaplan. Manuscript collectively outlined and reviewed by all four authors.

Corresponding author

Correspondence to Eric Fu.

Ethics declarations

Ethics Approval

Not Applicable

Consent to Participate

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.

This article is part of the Topical Collection on Medicine

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fu, E., Wallace, K., Grayden, K. et al. A Review of Neural Stem Cell Transplant Therapy for Traumatic Spinal Cord Injury. SN Compr. Clin. Med. 3, 1586–1592 (2021). https://doi.org/10.1007/s42399-021-00910-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s42399-021-00910-7

Keywords

Search

Navigation