Dosing parameters for grafting human neural stem cells into sites of spinal cord injury

IF 4.2 2区医学 Q1 NEUROSCIENCES

Experimental Neurology Pub Date : 2025-09-22 DOI:10.1016/j.expneurol.2025.115480

J.H. Brock , C.A. Shevinsky , L. Graham , E. Staufenberg , K.R. Limon , T.J. Vokes , K. Archuleta , A. Blesch , P. Lu , M.H. Tuszynski

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Abstract

Grafts of neural stem cells into sites of spinal cord injury (SCI) in animal models support functional improvement by forming new synaptic relays across the lesion site. Efficacy has been demonstrated in mouse, rodent and rhesus monkey models of SCI after both thoracic and cervical level injury. In preparation for the initiation of clinical trials, it is important to establish the minimum effective dose and maximal tolerated dose of neural stem cells implanted into lesion sites. Accordingly, we grafted our human embryonic stem cell-derived spinal cord neural progenitor cells into sites of rat thoracic spinal cord contusion at five different doses ranging from 10,000 to 400,000 cells/μl. 12-weeks post-grafting, spinal cord tissue was assessed for graft filling, neuronal differentiation, graft axonal outgrowth and host axonal ingrowth. We now report that in rats; the minimum effective dose is 100,000 cells/μl and the maximum tolerated dose is 400,000 cells/μl. These cell concentrations constitute a potential cell dose range for testing in human clinical trials.

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人神经干细胞在脊髓损伤部位移植的剂量参数。

在动物模型中，将神经干细胞移植到脊髓损伤部位，通过在损伤部位形成新的突触传导，支持功能改善。在小鼠、啮齿动物和恒河猴胸椎和颈椎水平损伤后的脊髓损伤模型中已经证明了其疗效。在准备启动临床试验时，确定病变部位植入神经干细胞的最小有效剂量和最大耐受剂量是很重要的。因此，我们将人胚胎干细胞衍生的脊髓神经祖细胞以5种不同的剂量移植到大鼠胸段脊髓挫伤部位，剂量范围为1万至40万细胞/μl。移植后12周，评估脊髓组织移植物填充、神经元分化、移植物轴突外植和宿主轴突长入情况。我们现在在老鼠身上报告；最小有效剂量为10万个细胞/μl，最大耐受剂量为40万个细胞/μl。这些细胞浓度构成了用于人体临床试验的潜在细胞剂量范围。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental Neurology 医学-神经科学

CiteScore

10.10

自引率

3.80%

发文量

258

审稿时长

42 days

期刊介绍： Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.