{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T09:13:34Z","timestamp":1793697214689,"version":"4.5.1"},"reference-count":15,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"6","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,1]]},"abstract":"<jats:sec>\n<jats:title>OBJECTIVE<\/jats:title>\n<jats:p>The primary objective of this study was to evaluate the safety of 3 escalating doses of oligodendrocyte progenitor cells (LCTOPC1; previously known as GRNOPC1 and AST-OPC1) administered at a single time point between 21 and 42 days postinjury to participants with subacute cervical spinal cord injuries (SCIs). The secondary objective was to evaluate changes in neurological function following administration of LCTOPC1.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>METHODS<\/jats:title>\n<jats:p>This study was designed as an open-label, dose-escalation, multicenter clinical trial. Twenty-five participants with C4\u20137 American Spinal Injury Association Impairment Scale grade A or B injuries received a single dose of either 2 \u00d7 10<jats:sup>6<\/jats:sup>, 1 \u00d7 10<jats:sup>7<\/jats:sup>, or 2 \u00d7 10<jats:sup>7<\/jats:sup> LCTOPC1 delivered via intraparenchymal injection into the spinal cord at the site of injury using a custom-designed syringe positioning device. Low-dose tacrolimus was administered until day 60. Outcome measures included adverse event (AE) monitoring and neurological function as measured by the International Standards for Neurological Classification of Spinal Cord Injury.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>RESULTS<\/jats:title>\n<jats:p>All 25 participants experienced at least one AE, with a total of 534 AEs (32 study-related vs 502 study-unrelated anticipated complications of SCI) reported at the completion of 1-year follow-up. There were 29 serious AEs reported. Two grade 3 serious AEs (CSF leak in one participant and a bacterial infection in another) were considered related to the injection procedure and to immunosuppression with tacrolimus, respectively. The CSF leakage resolved with sequelae, including self-limited altered mental status, and the infection resolved with antibiotic therapy. For all participants, MRI scans demonstrated no evidence of an enlarging mass, spinal cord damage related to the injection procedure, inflammatory lesions in the spinal cord, or masses in the ventricular system. At 1-year follow-up, 21\/22 (96%) of the intention-to-treat group recovered one or more levels of neurological function on at least one side of their body, and 7\/22 (32%) recovered two or more levels of neurological function on at least one side of their body.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>CONCLUSIONS<\/jats:title>\n<jats:p>LCTOPC1 can be safely administered to participants in the subacute period after cervical SCI. The injection procedure, low-dose temporary immunosuppression regimen, and LCTOPC1 were well tolerated. The safety and neurological function data support further investigation to determine the efficacy of LCTOPC1 in the treatment of SCI.<\/jats:p>\n<jats:p>Clinical trial registration no.: NCT02302157 (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>)<\/jats:p>\n<\/jats:sec>","DOI":"10.3171\/2022.5.spine22167","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T08:59:13Z","timestamp":1657270753000},"page":"812-820","source":"Crossref","is-referenced-by-count":69,"title":["A phase 1\/2a dose-escalation study of oligodendrocyte progenitor cells in individuals with subacute cervical spinal cord injury"],"prefix":"10.3171","volume":"37","author":[{"given":"Richard G.","family":"Fessler","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Rush University Medical Center, Chicago, Illinois;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Ehsanian","sequence":"additional","affiliation":[{"name":"Division of Physical Medicine and Rehabilitation, Department of Orthopedics & Rehabilitation, University of New Mexico School of Medicine, Albuquerque, New Mexico;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles Y.","family":"Liu","sequence":"additional","affiliation":[{"name":"USC Neurorestoration Center, Los Angeles;"},{"name":"Department of Neurological Surgery, USC Keck School of Medicine, Los Angeles;"},{"name":"Rancho Los Amigos National Rehabilitation Center, Downey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary K.","family":"Steinberg","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Jones","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University, Philadelphia, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane S.","family":"Lebkowski","sequence":"additional","affiliation":[{"name":"Asterias Biotherapeutics, a wholly owned subsidiary of Lineage Cell Therapeutics, Carlsbad;"},{"name":"Regenerative Patch Technologies, LLC, Menlo Park;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward D.","family":"Wirth","sequence":"additional","affiliation":[{"name":"Asterias Biotherapeutics, a wholly owned subsidiary of Lineage Cell Therapeutics, Carlsbad;"},{"name":"Aspen Neuroscience, San Diego; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen L.","family":"McKenna","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, California;"},{"name":"Department of Physical Medicine and Rehabilitation, Santa Clara Valley Medical Center, San Jose, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"issue":"8","key":"b1","series-title":"Regen Med","first-page":"939","article-title":"Preclinical safety of human embryonic stem cell-derived oligodendrocyte progenitors supporting clinical trials in spinal cord injury","volume":"10","author":"Priest CA","year":"2015","unstructured":"Priest CA, Manley NC, Denham J, Wirth ED III, Lebkowski JS. Preclinical safety of human embryonic stem cell-derived oligodendrocyte progenitors supporting clinical trials in spinal cord injury. Regen Med. 2015;10(8):939\u2013958.26345388"},{"issue":"6","key":"b2","series-title":"Stem Cells Dev","first-page":"943","article-title":"Oligodendrocyte progenitor cells derived from human embryonic stem cells express neurotrophic factors","volume":"15","author":"Zhang YW","year":"2006","unstructured":"Zhang YW, Denham J, Thies RS. Oligodendrocyte progenitor cells derived from human embryonic stem cells express neurotrophic factors. Stem Cells Dev. 2006;15(6):943\u2013952.17253955"},{"issue":"19","key":"b3","series-title":"J Neurosci","first-page":"4694","article-title":"Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury","volume":"25","author":"Keirstead HS","year":"2005","unstructured":"Keirstead HS, Nistor G, Bernal G,  Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J Neurosci. 2005;25(19):4694\u20134705.15888645"},{"key":"b4","series-title":"Nature","article-title":"Human embryonic stem cell trial wins approval","author":"Wadman M","unstructured":"Wadman M. Human embryonic stem cell trial wins approval. Nature. Published online January 24, 2009. doi:10.1038\/news.2009.56"},{"key":"b5","article-title":"A Phase 1 Safety Study of GRNOPC1 in Patients With Neurologically Complete, Subacute, Spinal Cord Injury","author":"Lineage Cell Therapeutics, Inc.","unstructured":"Lineage Cell Therapeutics, Inc.. A Phase 1 Safety Study of GRNOPC1 in Patients With Neurologically Complete, Subacute, Spinal Cord Injury. NCT01217008. ClinicalTrials.gov. Accessed May 20, 2022. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01217008"},{"key":"b6","series-title":"J Neurosurg Spine","article-title":"Ten-year safety of pluripotent stem cell transplantation in acute thoracic spinal cord injury","author":"McKenna SL","unstructured":"McKenna SL, Ehsanian R, Liu CY,  Ten-year safety of pluripotent stem cell transplantation in acute thoracic spinal cord injury. J Neurosurg Spine. 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J Neurotrauma. 2008;25(6):677\u2013685.18578636"},{"issue":"10","key":"b9","series-title":"Stem Cells Transl Med","first-page":"1917","article-title":"Human embryonic stem cell-derived oligodendrocyte progenitor cells: preclinical efficacy and safety in cervical spinal cord injury","volume":"6","author":"Manley NC","year":"2017","unstructured":"Manley NC, Priest CA, Denham J, Wirth ED III, Lebkowski JS. Human embryonic stem cell-derived oligodendrocyte progenitor cells: preclinical efficacy and safety in cervical spinal cord injury. Stem Cells Transl Med. 2017;6(10):1917\u20131929.28834391"},{"issue":"3","key":"b10","series-title":"J Neurosurg Spine","first-page":"389","article-title":"Safety of direct injection of oligodendrocyte progenitor cells into the spinal cord of uninjured G\u00f6ttingen minipigs","volume":"35","author":"Fessler RG","year":"2021","unstructured":"Fessler RG, Liu CY, McKenna S,  Safety of direct injection of oligodendrocyte progenitor cells into the spinal cord of uninjured G\u00f6ttingen minipigs. J Neurosurg Spine. 2021;35(3):389\u2013397."},{"issue":"2","key":"b11","series-title":"J Spinal Cord Med","first-page":"166","article-title":"Reliability and repeatability of the motor and sensory examination of the International Standards for Neurological Classification of Spinal Cord Injury","volume":"31","author":"Marino RJ","year":"2008","unstructured":"Marino RJ, Jones L, Kirshblum S, Tal J, Dasgupta A. Reliability and repeatability of the motor and sensory examination of the International Standards for Neurological Classification of Spinal Cord Injury. J Spinal Cord Med. 2008;31(2):166\u2013170.18581663"},{"issue":"2","key":"b12","series-title":"Top Spinal Cord Inj Rehabil","first-page":"1","article-title":"International Standards for Neurological Classification of Spinal Cord Injury: revised 2019","volume":"27","author":"Rupp R","year":"2021","unstructured":"Rupp R, Biering-S\u00f8rensen F, Burns SP,  International Standards for Neurological Classification of Spinal Cord Injury: revised 2019. Top Spinal Cord Inj Rehabil. 2021;27(2):1\u201322.34108832"},{"issue":"11","key":"b13","series-title":"Arch Phys Med Rehabil","first-page":"1485","article-title":"Predicting community reintegration after spinal cord injury from demographic and injury characteristics","volume":"80","author":"Whiteneck G","year":"1999","unstructured":"Whiteneck G, Tate D, Charlifue S. Predicting community reintegration after spinal cord injury from demographic and injury characteristics. Arch Phys Med Rehabil. 1999;80(11):1485\u20131491.10569445"},{"issue":"1","key":"b14","series-title":"World J Orthop","first-page":"24","article-title":"Chronic complications of spinal cord injury","volume":"6","author":"Sezer N","year":"2015","unstructured":"Sezer N, Akku\u015f S, U\u011furlu FG. Chronic complications of spinal cord injury. World J Orthop. 2015;6(1):24\u201333.25621208"},{"issue":"1","key":"b15","series-title":"Top Spinal Cord Inj Rehabil","first-page":"1","article-title":"Outcome measures for acute\/subacute cervical sensorimotor complete (AIS-A) spinal cord injury during a phase 2 clinical trial","volume":"18","author":"Steeves JD","year":"2012","unstructured":"Steeves JD, Lammertse DP, Kramer JLK,  Outcome measures for acute\/subacute cervical sensorimotor complete (AIS-A) spinal cord injury during a phase 2 clinical trial. 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