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间充质干细胞外泌体的见解:一种用于神经退行性疾病的前瞻性无细胞再生医学。

Insights of Extracellular Vesicles of Mesenchymal Stem Cells: a Prospective Cell-Free Regenerative Medicine for Neurodegenerative Disorders.

作者信息

Vatsa P, Negi R, Ansari U A, Khanna V K, Pant A B

机构信息

System Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, Mahatma Gandhi Marg, P.O. Box No. 80, Lucknow, Uttar Pradesh, 226001, India.

CSIR-Human Resource Development Centre (CSIR-HRDC) Campus, Academy of Scientific and Innovative Research (AcSIR), Postal Staff College Area, Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh, 201002, India.

出版信息

Mol Neurobiol. 2022 Jan;59(1):459-474. doi: 10.1007/s12035-021-02603-7. Epub 2021 Oct 29.

Abstract

Mesenchymal stem cells (MSCs) are multipotent, adult stem cells which are found in numerous tissues like the umbilical cord, Wharton's jelly, bone marrow, and adipose tissue. They possess the capacity of self-renewal by dividing and differentiating into various cellular lineages. Their characteristic therapeutic potential exploited so far has made them a desirable candidate in regenerative medicine. Neurodegenerative diseases (NDs) like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and ischemic stroke have been treated with MSCs and MSC-derived products. Over the past few decades, we have witnessed significant contributions in discovering the etiology of various NDs and their possible therapeutic solutions. One of the MSC-based therapeutics is extracellular vesicles (EVs), which contain multiple biologically active molecules like nucleic acids and proteins. The contents of EVs are ferried between cells for intercellular communication which then leads to regulation of the homeostasis of recipient cells. EVs serve as a considerable means of cell-free therapies like for tissue repair or regeneration as EVs can maintain therapeutically effective cargo of parent cells and are free of various ethical issues in cell-based therapies. Due to paucity of standard protocols in extraction procedures of EVs and their pharmacological properties and mechanisms, the development of new EV dependent therapies is challenging. With this review, an attempt has been made to annotate these mechanisms, which can help advance the novel therapeutic approaches towards the treat and define a more narrowed down approach for each ND to devise effective MSC-based therapies to cure and avert these diseases.

摘要

间充质干细胞(MSCs)是多能成体干细胞,存在于许多组织中,如脐带、华通氏胶、骨髓和脂肪组织。它们具有通过分裂和分化为各种细胞谱系进行自我更新的能力。迄今为止,它们独特的治疗潜力使其成为再生医学中理想的候选者。间充质干细胞及其衍生产品已被用于治疗神经退行性疾病(NDs),如阿尔茨海默病(AD)、帕金森病(PD)、亨廷顿舞蹈病(HD)、肌萎缩侧索硬化症(ALS)和缺血性中风。在过去几十年里,我们在发现各种神经退行性疾病的病因及其可能的治疗方法方面取得了重大进展。基于间充质干细胞的一种治疗方法是细胞外囊泡(EVs),它含有多种生物活性分子,如核酸和蛋白质。细胞外囊泡的内容物在细胞间传递,用于细胞间通讯,进而调节受体细胞的稳态。细胞外囊泡是一种重要的无细胞治疗手段,可用于组织修复或再生,因为它可以保持亲代细胞的治疗有效成分,并且不存在基于细胞治疗中的各种伦理问题。由于细胞外囊泡提取程序及其药理特性和机制缺乏标准方案,新的基于细胞外囊泡的治疗方法的开发具有挑战性。通过本综述,我们试图阐明这些机制,这有助于推进针对这些疾病的新型治疗方法,并为每种神经退行性疾病定义一种更具针对性的方法,以设计有效的基于间充质干细胞的治疗方法来治愈和预防这些疾病。

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