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提高用于神经疾病的人骨髓间充质干细胞质量和新鲜度的策略

Strategies to Improve the Quality and Freshness of Human Bone Marrow-Derived Mesenchymal Stem Cells for Neurological Diseases.

作者信息

Lee Da Yeon, Lee Sung Eun, Kwon Do Hyeon, Nithiyanandam Saraswathy, Lee Mi Ha, Hwang Ji Su, Basith Shaherin, Ahn Jung Hwan, Shin Tae Hwan, Lee Gwang

机构信息

Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea.

Department of Emergency Medicine, Ajou University School of Medicine, Suwon, Republic of Korea.

出版信息

Stem Cells Int. 2021 Sep 8;2021:8444599. doi: 10.1155/2021/8444599. eCollection 2021.

Abstract

Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) have been studied for their application to manage various neurological diseases, owing to their anti-inflammatory, immunomodulatory, paracrine, and antiapoptotic ability, as well as their homing capacity to specific regions of brain injury. Among mesenchymal stem cells, such as BM-MSCs, adipose-derived MSCs, and umbilical cord MSCs, BM-MSCs have many merits as cell therapeutic agents based on their widespread availability and relatively easy attainability and in vitro handling. For stem cell-based therapy with BM-MSCs, it is essential to perform ex vivo expansion as low numbers of MSCs are obtained in bone marrow aspirates. Depending on timing, before hBM-MSC transplantation into patients, after detaching them from the culture dish, cell viability, deformability, cell size, and membrane fluidity are decreased, whereas reactive oxygen species generation, lipid peroxidation, and cytosolic vacuoles are increased. Thus, the quality and freshness of hBM-MSCs decrease over time after detachment from the culture dish. Especially, for neurological disease cell therapy, the deformability of BM-MSCs is particularly important in the brain for the development of microvessels. As studies on the traditional characteristics of hBM-MSCs before transplantation into the brain are very limited, omics and machine learning approaches are needed to evaluate cell conditions with indepth and comprehensive analyses. Here, we provide an overview of hBM-MSCs, the application of these cells to various neurological diseases, and improvements in their quality and freshness based on integrated omics after detachment from the culture dish for successful cell therapy.

摘要

人骨髓间充质干细胞(hBM-MSCs)因其抗炎、免疫调节、旁分泌和抗凋亡能力,以及对脑损伤特定区域的归巢能力,已被研究用于治疗各种神经系统疾病。在间充质干细胞中,如骨髓间充质干细胞(BM-MSCs)、脂肪来源的间充质干细胞和脐带间充质干细胞,BM-MSCs作为细胞治疗剂具有许多优点,因为它们广泛可用,相对容易获得且易于体外处理。对于基于BM-MSCs的干细胞治疗,由于在骨髓抽吸物中获得的间充质干细胞数量较少,进行体外扩增至关重要。根据时间不同,在将hBM-MSCs移植到患者体内之前,从培养皿中分离后,细胞活力、变形性、细胞大小和膜流动性会降低,而活性氧生成、脂质过氧化和胞质空泡会增加。因此,hBM-MSCs从培养皿分离后的质量和新鲜度会随时间下降。特别是对于神经系统疾病的细胞治疗,BM-MSCs的变形性在脑微血管发育中尤为重要。由于在将hBM-MSCs移植到脑内之前对其传统特性的研究非常有限,因此需要组学和机器学习方法来深入全面地评估细胞状况。在此,我们概述了hBM-MSCs、这些细胞在各种神经系统疾病中的应用,以及为实现成功的细胞治疗,在从培养皿分离后基于综合组学对其质量和新鲜度的改善。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e85/8445711/1c66a255f5b8/SCI2021-8444599.001.jpg

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