研究动态
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如何才能克服脊髓损伤干细胞治疗中的临床安全性和疗效问题?

How can clinical safety and efficacy concerns in stem cell therapy for spinal cord injury be overcome?

发表日期:2023 Aug 06
作者: Nader Hejrati, Raymond Wong, Mohamad Khazaei, Michael G Fehlings
来源: Stem Cell Research & Therapy

摘要:

脊髓损伤(SCI)可能导致严重的神经功能障碍。尽管科学和医学取得了进展,但在SCI领域仍缺乏临床有效的再生治疗方法,包括干细胞治疗。本文讨论与安全有效使用干细胞治疗SCI相关的转化难题,重点关注间充质干细胞(MSCs)、神经干细胞(NSCs)、施万细胞(SCs)、嗅神经鞘细胞(OECs)、寡突胶质细胞前体细胞(OPCs)、胚胎干细胞(ESCs)和诱导多能干细胞(iPSCs)。我们讨论了通过以下途径增强细胞为基础治疗策略的疗效:i)解决患者异质性和提高患者选择的方法;ii)选择细胞类型、细胞来源、细胞发育阶段和输送技术;iii)提高移植物的整合性和减轻免疫介导的移植物排斥;iv)确保细胞的可获得性。此外,我们还回顾了优化治疗结果的策略,包括康复的组合使用,并讨论了如何减轻与干细胞为基础治疗策略相关的肿瘤形成的潜在风险,以及如何增强细胞的存活率。基础科学研究将推动干细胞为基础治疗SCI的转化进展。遗传学、血清学和影像学生物标志物可能实现个体化的细胞治疗。此外,将需要组合策略来增强移植物的存活、迁移和功能整合,以实现精准干预。
Spinal cord injury (SCI) can lead to severe neurological dysfunction. Despite scientific and medical advances, clinically effective regenerative therapies including stem cells are lacking for SCI.This paper discusses translational challenges related to the safe, effective use of stem cells for SCI, with a focus on mesenchymal stem cells (MSCs), neural stem cells (NSCs), Schwann cells (SCs), olfactory ensheathing cells (OECs), oligodendrocyte precursor cells (OPCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). We discuss approaches to enhance efficacy of cell-based strategies by i) addressing patient heterogeneity and enhancing patient selection; ii) selecting cell type, cell source, cell developmental stage, and delivery technique; iii) enhancing graft integration and mitigating immune-mediated graft rejection; and iv) ensuring availability of cells. Additionally, we review strategies to optimize outcomes including combinatorial use of rehabilitation and discuss ways to mitigate potential risks of tumor formation associated with stem cell-based strategies and enhance cellular viability.Basic science research will drive translational advances to develop stem cell-based therapies for SCI. Genetic, serological, and imaging biomarkers may enable individualization of cell-based treatments. Moreover, combinatorial strategies will be required to enhance graft survival, migration and functional integration, to enable precision-based intervention.