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

doi:10.1093/neuros/nyx250

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

Neurosurgery

Research output: Contribution to journal › Article › peer-review

118 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 language	English (US)
Pages (from-to)	562-575
Number of pages	14
Journal	Clinical neurosurgery
Volume	82
Issue number	4
DOIs	https://doi.org/10.1093/neuros/nyx250
State	Published - Apr 1 2018

Bibliographical note

Publisher Copyright:
Copyright © 2017 by the Congress of Neurological Surgeons.

Keywords

Cervical
Injection
Spinal cord injury
Stem cells
Thoracic

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10.1093/neuros/nyx250

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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

Levi, AD, Okonkwo, DO, Park, P, Jenkins, AL, Kurpad, SN, Parr, AM, Ganju, A, Aarabi, B, Kim, D, Casha, S, Fehlings, MG, Harrop, JS, Anderson, KD, 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, vol. 82, no. 4, pp. 562-575. https://doi.org/10.1093/neuros/nyx250

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

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.",

keywords = "Cervical, Injection, Spinal cord injury, Stem cells, Thoracic",

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

note = "Publisher Copyright: Copyright {\textcopyright} 2017 by the Congress of Neurological Surgeons.",

year = "2018",

month = apr,

day = "1",

doi = "10.1093/neuros/nyx250",

language = "English (US)",

volume = "82",

pages = "562--575",

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TY - JOUR

T1 - Emerging safety of intramedullary transplantation of human neural stem cells in chronic cervical and thoracic spinal cord injury

AU - Levi, Allan D.

AU - Okonkwo, David O.

AU - Park, Paul

AU - Jenkins, Arthur L.

AU - Kurpad, Shekar N.

AU - Parr, Ann M.

AU - Ganju, Aruna

AU - Aarabi, Bizhan

AU - Kim, Dong

AU - Casha, Steven

AU - Fehlings, Michael G.

AU - Harrop, James S.

AU - Anderson, Kim D.

AU - Gage, Allyson

AU - Hsieh, Jane

AU - Huhn, Stephen

AU - Curt, Armin

AU - Guzman, Raphael

PY - 2018/4/1

Y1 - 2018/4/1

N2 - 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.

AB - 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.

KW - Cervical

KW - Injection

KW - Spinal cord injury

KW - Stem cells

KW - Thoracic

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DO - 10.1093/neuros/nyx250

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SN - 0148-396X

VL - 82

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JO - Clinical neurosurgery

JF - Clinical neurosurgery

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ER -

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

Abstract

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