Emerging safety of intramedullary transplantation of human neural stem cells in chronic cervical and thoracic spinal cord injury

Allan D. Levi, David O. Okonkwo, Paul Park, Arthur L. Jenkins, Shekar N. Kurpad, Ann M. Parr, Aruna Ganju, Bizhan Aarabi, Dong Kim, Steven Casha, Michael G. Fehlings, James S. Harrop, Kim D. Anderson, Allyson Gage, Jane Hsieh, Stephen Huhn, Armin Curt, Raphael Guzman

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

BACKGROUND: Human central nervous system stem cells (HuCNS-SC) are multipotent adult stem cells with successful engraftment, migration, and region-appropriate differentiation after spinal cord injury (SCI). OBJECTIVE: To present data on the surgical safety profile and feasibility of multiple intramedullary perilesional injections of HuCNS-SC after SCI. METHODS: Intramedullary free-hand (manual) transplantation of HuCNS-SC cells was performed in subjects with thoracic (n = 12) and cervical (n = 17) complete and sensory incomplete chronic traumatic SCI. RESULTS: Intramedullary stem cell transplantation needle times in the thoracic cohort (20MHuCNS-SC)were 19:30 min and total injection time was 42:15 min. The cervical cohort I (n = 6), demonstrated that escalating doses of HuCNS-SC up to 40 M range were well tolerated. In cohort II (40 M, n = 11), the intramedullary stem cell transplantation needle times and total injection time was 26:05 ± 1:08 and 58:14 ± 4:06 min, respectively. In the first year after injection, there were 4 serious adverse events in 4 of the 12 thoracic subjects and 15 serious adverse events in 9 of the 17 cervical patients. No safety concerns were considered related to the cells or the manual intramedullary injection. Cervical magnetic resonance images demonstrated mild increased T2 signal change in 8 of 17 transplanted subjects without motor decrements or emerging neuropathic pain. All T2 signal change resolved by 6 to 12 mo post-transplant. CONCLUSION: A total cell dose of 20 M cells via 4 and up to 40 M cells via 8 perilesional intramedullary injections after thoracic and cervical SCI respectively proved safe and feasible using a manual injection technique.

Original languageEnglish (US)
Pages (from-to)562-575
Number of pages14
JournalClinical neurosurgery
Volume82
Issue number4
DOIs
StatePublished - Apr 1 2018

Keywords

  • Cervical
  • Injection
  • Spinal cord injury
  • Stem cells
  • Thoracic

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    Levi, A. D., Okonkwo, D. O., Park, P., Jenkins, A. L., Kurpad, S. N., Parr, A. M., Ganju, A., Aarabi, B., Kim, D., Casha, S., Fehlings, M. G., Harrop, J. S., Anderson, K. D., Gage, A., Hsieh, J., Huhn, S., Curt, A., & Guzman, R. (2018). Emerging safety of intramedullary transplantation of human neural stem cells in chronic cervical and thoracic spinal cord injury. Clinical neurosurgery, 82(4), 562-575. https://doi.org/10.1093/neuros/nyx250