title: Preclinical Efficacy Failure of Human CNS-Derived Stem Cells for Use in the Pathway Study of Cervical Spinal Cord Injury.
abstract: We previously showed the efficacy of multiple research cell lines (RCLs) of human CNS neural stem cells (HuCNS-SCs) in mouse and rat models of thoracic spinal cord injury (SCI), supporting a thoracic SCI clinical trial. Experts recommend in vivo preclinical testing of the intended clinical cell lot/line (CCL) in models with validity for the planned clinical target. We therefore tested the efficacy of two HuCNS-SC lines in cervical SCI: one RCL, and one CCL intended for use in the Pathway Study of cervical SCI in man. We assessed locomotor recovery and sensory function, as well as engraftment, migration, and fate. No evidence of efficacy of the CCL was observed; some data suggested a negative impact of the CCL on outcomes. These data raise questions about the development and validation of potency/comparability assays for clinical testing of cell products, and lack of US Food and Drug Administration requirements for in vivo testing of intended clinical cell lines.
authors.affiliation: Sue & Bill Gross Stem Cell Center, University of California-Irvine, Irvine, CA 92697, USA; Physical & Medical Rehabilitation, University of California-Irvine, Irvine, CA 92697, USA; Institute for Memory Impairments & Neurological Disorders, University of California-Irvine, Irvine, CA 92697, USA; Anatomy & Neurobiology, University of California-Irvine, Irvine, CA 92697, USA. Electronic address: aja@uci.edu.
authors.forename: Aileen J
authors.initials: AJ
authors.lastname: Anderson
authors.affiliation: Sue & Bill Gross Stem Cell Center, University of California-Irvine, Irvine, CA 92697, USA; Institute for Memory Impairments & Neurological Disorders, University of California-Irvine, Irvine, CA 92697, USA.
authors.forename: Katja M
authors.initials: KM
authors.lastname: Piltti
authors.affiliation: Sue & Bill Gross Stem Cell Center, University of California-Irvine, Irvine, CA 92697, USA; Institute for Memory Impairments & Neurological Disorders, University of California-Irvine, Irvine, CA 92697, USA.
authors.forename: Mitra J
authors.initials: MJ
authors.lastname: Hooshmand
authors.affiliation: Sue & Bill Gross Stem Cell Center, University of California-Irvine, Irvine, CA 92697, USA; Institute for Memory Impairments & Neurological Disorders, University of California-Irvine, Irvine, CA 92697, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Nishi
authors.affiliation: Sue & Bill Gross Stem Cell Center, University of California-Irvine, Irvine, CA 92697, USA; Physical & Medical Rehabilitation, University of California-Irvine, Irvine, CA 92697, USA; Institute for Memory Impairments & Neurological Disorders, University of California-Irvine, Irvine, CA 92697, USA; Anatomy & Neurobiology, University of California-Irvine, Irvine, CA 92697, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Cummings
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D066193:Cervical Cord / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006085:Graft Survival; D006801:Humans; D008124:Locomotion; D051379:Mice; D009043:Motor Activity; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D020127:Recovery of Function; D015398:Signal Transduction; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology / Q000534:rehabilitation / Q000628:therapy; D033581:Stem Cell Transplantation; D013997:Time Factors; D016896:Treatment Outcome
keywords: FDA guidelines for cell therapies; RIGOR; cervical; efficacy; good manufacturing practices (GMP); human neural stem cells (hNSC); spinal cord injury (SCI)