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神经障碍的干细胞疗法:当前进展、挑战与未来展望。

Stem cell therapies for neurological disorders: current progress, challenges, and future perspectives.

机构信息

Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran.

Nanoclub Elites Association, Tehran, Iran.

出版信息

Eur J Med Res. 2024 Jul 25;29(1):386. doi: 10.1186/s40001-024-01987-1.


DOI:10.1186/s40001-024-01987-1
PMID:39054501
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11270957/
Abstract

Stem cell-based therapies have emerged as a promising approach for treating various neurological disorders by harnessing the regenerative potential of stem cells to restore damaged neural tissue and circuitry. This comprehensive review provides an in-depth analysis of the current state of stem cell applications in primary neurological conditions, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, spinal cord injury (SCI), and other related disorders. The review begins with a detailed introduction to stem cell biology, discussing the types, sources, and mechanisms of action of stem cells in neurological therapies. It then critically examines the preclinical evidence from animal models and early human trials investigating the safety, feasibility, and efficacy of different stem cell types, such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), neural stem cells (NSCs), and induced pluripotent stem cells (iPSCs). While ESCs have been studied extensively in preclinical models, clinical trials have primarily focused on adult stem cells such as MSCs and NSCs, as well as iPSCs and their derivatives. We critically assess the current state of research for each cell type, highlighting their potential applications and limitations in different neurological conditions. The review synthesizes key findings from recent, high-quality studies for each neurological condition, discussing cell manufacturing, delivery methods, and therapeutic outcomes. While the potential of stem cells to replace lost neurons and directly reconstruct neural circuits is highlighted, the review emphasizes the critical role of paracrine and immunomodulatory mechanisms in mediating the therapeutic effects of stem cells in most neurological disorders. The article also explores the challenges and limitations associated with translating stem cell therapies into clinical practice, including issues related to cell sourcing, scalability, safety, and regulatory considerations. Furthermore, it discusses future directions and opportunities for advancing stem cell-based treatments, such as gene editing, biomaterials, personalized iPSC-derived therapies, and novel delivery strategies. The review concludes by emphasizing the transformative potential of stem cell therapies in revolutionizing the treatment of neurological disorders while acknowledging the need for rigorous clinical trials, standardized protocols, and multidisciplinary collaboration to realize their full therapeutic promise.

摘要

基于干细胞的疗法已经成为一种很有前途的方法,可以利用干细胞的再生潜力来修复受损的神经组织和电路,从而治疗各种神经疾病。本综述深入分析了干细胞在原发性神经疾病中的应用现状,包括帕金森病(PD)、阿尔茨海默病(AD)、肌萎缩侧索硬化症(ALS)、多发性硬化症(MS)、中风、脊髓损伤(SCI)和其他相关疾病。综述首先详细介绍了干细胞生物学,讨论了干细胞在神经治疗中的类型、来源和作用机制。然后,它批判性地检查了来自动物模型和早期人体试验的临床前证据,这些证据调查了不同干细胞类型(如胚胎干细胞(ESCs)、间充质干细胞(MSCs)、神经干细胞(NSCs)和诱导多能干细胞(iPSCs))的安全性、可行性和疗效。虽然 ESCs 在临床前模型中得到了广泛的研究,但临床试验主要集中在成人干细胞,如 MSCs 和 NSCs,以及 iPSCs 和它们的衍生物上。我们批判性地评估了每种细胞类型的当前研究状态,强调了它们在不同神经疾病中的潜在应用和局限性。综述综合了每个神经疾病的最近高质量研究的关键发现,讨论了细胞制造、传递方法和治疗结果。虽然强调了干细胞在取代丢失的神经元和直接重建神经回路方面的潜力,但该综述强调了旁分泌和免疫调节机制在介导大多数神经疾病中干细胞的治疗效果方面的关键作用。文章还探讨了将干细胞疗法转化为临床实践所面临的挑战和限制,包括与细胞来源、可扩展性、安全性和监管考虑有关的问题。此外,它还讨论了推进基于干细胞的治疗方法的未来方向和机会,例如基因编辑、生物材料、个性化 iPSC 衍生疗法和新型传递策略。该综述最后强调了干细胞疗法在彻底改变神经疾病治疗方面的变革潜力,同时承认需要进行严格的临床试验、标准化方案和多学科合作,以实现其全部治疗潜力。

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本文引用的文献

[1]
Stem cell therapies: a new era in the treatment of multiple sclerosis.

Front Neurol. 2024-5-9

[2]
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