用于颈脊髓损伤通路研究的人中枢神经系统来源干细胞的临床前疗效失败
Preclinical Efficacy Failure of Human CNS-Derived Stem Cells for Use in the Pathway Study of Cervical Spinal Cord Injury.
作者信息
Anderson Aileen J, Piltti Katja M, Hooshmand Mitra J, Nishi Rebecca A, Cummings Brian J
机构信息
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.
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.
出版信息
Stem Cell Reports. 2017 Feb 14;8(2):249-263. doi: 10.1016/j.stemcr.2016.12.018.
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.
我们之前已证明，人类中枢神经系统神经干细胞（HuCNS-SCs）的多种研究细胞系（RCLs）在胸段脊髓损伤（SCI）的小鼠和大鼠模型中具有疗效，这为一项胸段SCI临床试验提供了支持。专家建议，在对计划中的临床靶点有效的模型中，对预期的临床细胞批次/系（CCL）进行体内临床前测试。因此，我们测试了两种HuCNS-SC系在颈段SCI中的疗效：一种是RCL，另一种是打算用于人类颈段SCI通路研究的CCL。我们评估了运动功能恢复、感觉功能，以及植入、迁移和细胞命运。未观察到CCL有疗效的证据；一些数据表明CCL对结果有负面影响。这些数据引发了有关细胞产品临床测试效力/可比性测定方法的开发和验证的问题，以及美国食品药品监督管理局对预期临床细胞系进行体内测试缺乏要求的问题。
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