RESEARCH—HUMAN—CLINICAL STUDIES

Emerging Safety of Intramedullary Transplantation of Human Neural Stem Cells in Chronic Cervical and Thoracic Spinal Cord Injury

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

Author Information

Department of Neurological Surgery and the Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida

Department of Neurosurgery, University of Pittsburgh, Pittsburgh, Pennsylvania

Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan

Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New York

Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin

Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota

Department of Neurological Surgery, Northwestern Feinberg School of Medicine, Chicago, Illinois

Department of Neurosurgery, University of Maryland, College Park, Maryland

Department of Neurosurgery, University of Texas Health Science Center, Austin, Texas

Department of Clinical Neurosciences and the Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada

Division of Neurosurgery and Spinal Program, University Health Network, University of Toronto, Toronto, Ontario, Canada

Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania

Stem Cells Inc., Newark, California

Spinal Cord Injury Unit, Balgrist University Hospital, Zürich, Switzerland

Department of Neurosurgery, University Hospital Basel, Basel, Switzerland

Correspondence: Allan D. Levi, MD, PhD, Department of Neurological Surgery, University of Miami Miller School of Medicine, Lois Pope Life Center, 1095 NW 14th Terr, Suite 2–24, Miami, FL 33136. E-mail: [email protected]

Neurosurgery 82(4):p 562-575, April 2018. | DOI: 10.1093/neuros/nyx250

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 (20 M HuCNS-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.

Copyright © 2017 by the Congress of Neurological Surgeons

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