Comparative Outcomes of Intravenous, Intranasal, and Intracerebroventricular Transplantation of Human Neural Stem Cells in Mice Model of Ischemic Stroke.

Mengze Zhang, Yaying Song, Chong Xie, Yangtai Guan
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Abstract

Background: Transplantation of neural stem cells improves ischemic stroke outcomes in rodent models and is currently in the clinical test stage. However, the optimal delivery route to achieve improved efficacy remains undetermined.

Objective: This study aims to evaluate three more clinically feasible delivery routes: intravenous (IV), intranasal (IN), and intracerebroventricular (ICV). We compared the therapeutic efficacies of the three routes of transplanting human neural stem cells (hNSCs) into mice with permanent middle cerebral artery obstruction (pMCAO).

Methods: Behavioral tests and cresyl violet staining were used to evaluate the therapeutic efficacies of functional recovery and lesion volumes. The expression of proinflammatory cytokines and neurotrophic factors was measured by real-time PCR. The distribution and differentiation of hNSCs were determined by immunofluorescence staining. The effect on endogenous neurogenesis and astrocyte function were determined by immunofluorescence staining and western blot.

Results: hNSC transplantation using the three routes improved behavioral outcomes and reduced lesion volumes; IV transplantation of hNSCs results in earlier efficacy and improves the inflammatory microenvironment. The long-term distribution and differentiation of transplanted hNSCs in the peri-infarct areas can only be evaluated using ICV delivery. IV and ICV transplantation of hNSCs promote neurogenesis and modulate the dual function of astrocytes in the peri-infarct areas.

Conclusion: IV and IN delivery is suitable for repeated administration of hNSCs to achieve improved prognosis. Comparatively, ICV transplantation provides long-term efficacy at lower doses and fewer administration times.

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缺血性脑卒中小鼠模型中人神经干细胞静脉内、鼻内和脑室内移植的疗效比较。
背景:移植神经干细胞可改善啮齿类动物模型的缺血性中风预后,目前正处于临床试验阶段。然而,提高疗效的最佳给药途径仍未确定:本研究旨在评估三种临床可行的给药途径:静脉注射(IV)、鼻内注射(IN)和脑室内注射(ICV)。我们比较了将人神经干细胞(hNSCs)移植到永久性大脑中动脉阻塞(pMCAO)小鼠体内的三种途径的治疗效果:方法:采用行为测试和甲酚紫染色法评估小鼠功能恢复和病变体积的疗效。实时 PCR 检测促炎细胞因子和神经营养因子的表达。免疫荧光染色测定了 hNSCs 的分布和分化。结果:三种途径移植的 hNSCs 均能改善行为结果并减少病变体积;静脉移植的 hNSCs 能更早起效并改善炎症微环境。只有使用ICV给药才能评估移植的hNSCs在梗死周围区域的长期分布和分化情况。IV和ICV移植hNSCs可促进神经发生,并调节梗死周围区域星形胶质细胞的双重功能:结论:静脉注射和静脉输注适用于重复施用 hNSCs,以改善预后。结论:静脉注射和 IN 给药适用于重复给药 hNSCs 以改善预后,而 ICV 移植以较低的剂量和较少的给药时间获得长期疗效。
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