title: Safety of Autologous Human Schwann Cell Transplantation in Subacute Thoracic Spinal Cord Injury.
abstract: The rationale for implantation of autologous human Schwann cells (SCs) in persons with subacute spinal cord injury (SCI) is based on evidence that transplanted SCs are neuroprotective, support local axonal plasticity, and are capable of myelinating axons. A Phase I clinical trial was conducted to evaluate the safety of autologous human SC transplantation into the injury epicenter of six subjects with subacute SCI. The trial was an open-label, unblinded, non-randomized, non-placebo controlled study with a dose escalation design and standard medical rehabilitation. Participants were paraplegics with neurologically complete, trauma-induced spinal lesions. Autologous SCs were cultured in vitro from a sural nerve harvested from each participant and injected into the epicenter of the spinal lesion. Outcome measures for safety were protocol compliance, feasibility, adverse events, stability of neurological level, absence of detectable mass lesion, and the emergence of clinically significant neuropathic pain or muscle spasticity no greater than expected for a natural course cohort. One year post-transplantation, there were no surgical, medical, or neurological complications to indicate that the timing or procedure for the cell transplantation was unsafe. There were no adverse events or serious adverse events related to the cell therapy. There was no evidence of additional spinal cord damage, mass lesion, or syrinx formation. We conclude that it is feasible to identify eligible candidates, appropriately obtain informed consent, perform a peripheral nerve harvest to obtain SCs within 5-30 days of injury, and perform an intra-spinal transplantation of highly purified autologous SCs within 4-7 weeks of injury.
authors.affiliation: 1 The Miami Project to Cure Paralysis, The University of Miami Miller School of Medicine , Miami, Florida.|2 Department of Neurological Surgery, The University of Miami Miller School of Medicine , Miami, Florida.
authors.forename: Kim D
authors.initials: KD
authors.lastname: Anderson
authors.affiliation: 1 The Miami Project to Cure Paralysis, The University of Miami Miller School of Medicine , Miami, Florida.|2 Department of Neurological Surgery, The University of Miami Miller School of Medicine , Miami, Florida.|3 The Neuroscience Program, The University of Miami Miller School of Medicine , Miami, Florida.
authors.forename: James D
authors.initials: JD
authors.lastname: Guest
authors.affiliation: 1 The Miami Project to Cure Paralysis, The University of Miami Miller School of Medicine , Miami, Florida.|2 Department of Neurological Surgery, The University of Miami Miller School of Medicine , Miami, Florida.|3 The Neuroscience Program, The University of Miami Miller School of Medicine , Miami, Florida.|4 Department of Cell Biology, The University of Miami Miller School of Medicine , Miami, Florida.|5 Department of Neurology, The University of Miami Miller School of Medicine , Miami, Florida.|6 Department of The Interdisciplinary Stem Cell Institute, The University of Miami Miller School of Medicine , Miami, Florida.
authors.forename: W Dalton
authors.initials: WD
authors.lastname: Dietrich
authors.affiliation: 1 The Miami Project to Cure Paralysis, The University of Miami Miller School of Medicine , Miami, Florida.|2 Department of Neurological Surgery, The University of Miami Miller School of Medicine , Miami, Florida.|3 The Neuroscience Program, The University of Miami Miller School of Medicine , Miami, Florida.|4 Department of Cell Biology, The University of Miami Miller School of Medicine , Miami, Florida.|5 Department of Neurology, The University of Miami Miller School of Medicine , Miami, Florida.|6 Department of The Interdisciplinary Stem Cell Institute, The University of Miami Miller School of Medicine , Miami, Florida.
authors.forename: Mary
authors.initials: M
authors.lastname: Bartlett Bunge
authors.affiliation: 7 Department of Psychiatry, The University of Miami Miller School of Medicine , Miami, Florida.
authors.forename: Rosie
authors.initials: R
authors.lastname: Curiel
authors.affiliation: 1 The Miami Project to Cure Paralysis, The University of Miami Miller School of Medicine , Miami, Florida.|2 Department of Neurological Surgery, The University of Miami Miller School of Medicine , Miami, Florida.
authors.forename: Marine
authors.initials: M
authors.lastname: Dididze
authors.affiliation: 1 The Miami Project to Cure Paralysis, The University of Miami Miller School of Medicine , Miami, Florida.|2 Department of Neurological Surgery, The University of Miami Miller School of Medicine , Miami, Florida.|5 Department of Neurology, The University of Miami Miller School of Medicine , Miami, Florida.|8 Department of Orthopaedics, The University of Miami Miller School of Medicine , Miami, Florida.|9 Department of Rehabilitation Medicine, The University of Miami Miller School of Medicine , Miami, Florida.
authors.forename: Barth A
authors.initials: BA
authors.lastname: Green
authors.affiliation: 1 The Miami Project to Cure Paralysis, The University of Miami Miller School of Medicine , Miami, Florida.|6 Department of The Interdisciplinary Stem Cell Institute, The University of Miami Miller School of Medicine , Miami, Florida.
authors.forename: Aisha
authors.initials: A
authors.lastname: Khan
authors.affiliation: 1 The Miami Project to Cure Paralysis, The University of Miami Miller School of Medicine , Miami, Florida.|2 Department of Neurological Surgery, The University of Miami Miller School of Medicine , Miami, Florida.|3 The Neuroscience Program, The University of Miami Miller School of Medicine , Miami, Florida.|6 Department of The Interdisciplinary Stem Cell Institute, The University of Miami Miller School of Medicine , Miami, Florida.|11 Bruce W. Carter Department of Veterans Affairs Medical Center , Miami, Florida.
authors.forename: Damien D
authors.initials: DD
authors.lastname: Pearse
authors.affiliation: 10 Department of Radiology, The University of Miami Miller School of Medicine , Miami, Florida.
authors.forename: Efrat
authors.initials: E
authors.lastname: Saraf-Lavi
authors.affiliation: 1 The Miami Project to Cure Paralysis, The University of Miami Miller School of Medicine , Miami, Florida.|2 Department of Neurological Surgery, The University of Miami Miller School of Medicine , Miami, Florida.|3 The Neuroscience Program, The University of Miami Miller School of Medicine , Miami, Florida.|9 Department of Rehabilitation Medicine, The University of Miami Miller School of Medicine , Miami, Florida.|11 Bruce W. Carter Department of Veterans Affairs Medical Center , Miami, Florida.
authors.forename: Eva
authors.initials: E
authors.lastname: Widerström-Noga
authors.affiliation: 1 The Miami Project to Cure Paralysis, The University of Miami Miller School of Medicine , Miami, Florida.|2 Department of Neurological Surgery, The University of Miami Miller School of Medicine , Miami, Florida.
authors.forename: Patrick
authors.initials: P
authors.lastname: Wood
authors.affiliation: 1 The Miami Project to Cure Paralysis, The University of Miami Miller School of Medicine , Miami, Florida.|2 Department of Neurological Surgery, The University of Miami Miller School of Medicine , Miami, Florida.|8 Department of Orthopaedics, The University of Miami Miller School of Medicine , Miami, Florida.
authors.forename: Allan D
authors.initials: AD
authors.lastname: Levi
mesh_terms: D000328:Adult; D006801:Humans; D008297:Male; D012583:Schwann Cells / Q000637:transplantation*; D013119:Spinal Cord Injuries / Q000628:therapy*; D014182:Transplantation, Autologous / Q000009:adverse effects / Q000379:methods; D055815:Young Adult
keywords: Schwann cells; autologous transplantation; human; paraplegia; spinal cord injury