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将线粒体生物学融入神经退行性疾病的创新细胞疗法

Integrating Mitochondrial Biology into Innovative Cell Therapies for Neurodegenerative Diseases.

作者信息

Ore Adaleiz, Angelastro James M, Giulivi Cecilia

机构信息

Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA.

Department of Chemical Engineering, School of Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.

出版信息

Brain Sci. 2024 Sep 5;14(9):899. doi: 10.3390/brainsci14090899.

Abstract

The role of mitochondria in neurodegenerative diseases is crucial, and recent developments have highlighted its significance in cell therapy. Mitochondrial dysfunction has been implicated in various neurodegenerative disorders, including Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's diseases. Understanding the impact of mitochondrial biology on these conditions can provide valuable insights for developing targeted cell therapies. This mini-review refocuses on mitochondria and emphasizes the potential of therapies leveraging mesenchymal stem cells, embryonic stem cells, induced pluripotent stem cells, stem cell-derived secretions, and extracellular vesicles. Mesenchymal stem cell-mediated mitochondria transfer is highlighted for restoring mitochondrial health in cells with dysfunctional mitochondria. Additionally, attention is paid to gene-editing techniques such as mito-CRISPR, mitoTALENs, mito-ZNFs, and DdCBEs to ensure the safety and efficacy of stem cell treatments. Challenges and future directions are also discussed, including the possible tumorigenic effects of stem cells, off-target effects, disease targeting, immune rejection, and ethical issues.

摘要

线粒体在神经退行性疾病中的作用至关重要,最近的进展凸显了其在细胞治疗中的重要性。线粒体功能障碍与多种神经退行性疾病有关,包括阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和亨廷顿病。了解线粒体生物学对这些疾病的影响可为开发靶向细胞疗法提供有价值的见解。本综述重新聚焦于线粒体,并强调利用间充质干细胞、胚胎干细胞、诱导多能干细胞、干细胞衍生分泌物和细胞外囊泡进行治疗的潜力。间充质干细胞介导的线粒体转移被强调可恢复线粒体功能异常细胞中的线粒体健康。此外,还关注了基因编辑技术,如线粒体CRISPR、线粒体转录激活样效应因子核酸酶(mitoTALENs)、线粒体锌指核酸酶(mito-ZNFs)和碱基编辑器(DdCBEs),以确保干细胞治疗的安全性和有效性。还讨论了挑战和未来方向,包括干细胞可能的致瘤作用、脱靶效应、疾病靶向、免疫排斥和伦理问题。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f7e/11429837/e980de53b6ce/brainsci-14-00899-g001.jpg

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