{"title":"利用细胞迁移动力学区分衰老和成熟的人类间充质干细胞","authors":"Farshad Amiri, Panagiotis Mistriotis","doi":"10.1007/s12195-024-00807-0","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>The suboptimal clinical performance of human mesenchymal stem cells (hMSCs) has raised concerns about their therapeutic potential. One major contributing factor to this issue is the heterogeneous nature of hMSCs. Senescent cell accumulation during stem cell expansion is a key driver of MSC heterogeneity. Current methodologies to eradicate senescent hMSCs have either shown limited success or lack clinical relevance. This study leverages the inherent capacity of hMSCs to migrate toward damaged tissues as a means to discern senescent from presenescent stem cells. Given the established deficiency of senescent cells to migrate through physiologically relevant environments, we hypothesized that a microfluidic device, designed to emulate key facets of in vivo cell motility, could serve as a platform for identifying presenescent cells.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We employed a Y-shaped microchannel assay, which allows fine-tuning of fluid flow rates and the degree of confinement.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Highly migratory hMSCs detected by the device not only demonstrate increased speed, smaller size, and higher proliferative capacity but also manifest reduced DNA damage and senescence compared to non-migratory cells. Additionally, this assay detects presenescent cells in experiments with mixed early and late passage cells. The introduction of fluid flow through the device can further increase the fraction of highly motile stem cells, improving the assay's effectiveness to remove senescent hMSCs.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Collectively, this assay facilitates the detection and isolation of a highly potent stem cell subpopulation. Given the positive correlation between the migratory potential of administered MSCs and the long-term clinical outcome, delivering homogeneous, highly motile presenescent hMSCs may benefit patient outcomes.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"31 1","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Leveraging Cell Migration Dynamics to Discriminate Between Senescent and Presenescent Human Mesenchymal Stem Cells\",\"authors\":\"Farshad Amiri, Panagiotis Mistriotis\",\"doi\":\"10.1007/s12195-024-00807-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Purpose</h3><p>The suboptimal clinical performance of human mesenchymal stem cells (hMSCs) has raised concerns about their therapeutic potential. One major contributing factor to this issue is the heterogeneous nature of hMSCs. Senescent cell accumulation during stem cell expansion is a key driver of MSC heterogeneity. Current methodologies to eradicate senescent hMSCs have either shown limited success or lack clinical relevance. This study leverages the inherent capacity of hMSCs to migrate toward damaged tissues as a means to discern senescent from presenescent stem cells. Given the established deficiency of senescent cells to migrate through physiologically relevant environments, we hypothesized that a microfluidic device, designed to emulate key facets of in vivo cell motility, could serve as a platform for identifying presenescent cells.</p><h3 data-test=\\\"abstract-sub-heading\\\">Methods</h3><p>We employed a Y-shaped microchannel assay, which allows fine-tuning of fluid flow rates and the degree of confinement.</p><h3 data-test=\\\"abstract-sub-heading\\\">Results</h3><p>Highly migratory hMSCs detected by the device not only demonstrate increased speed, smaller size, and higher proliferative capacity but also manifest reduced DNA damage and senescence compared to non-migratory cells. Additionally, this assay detects presenescent cells in experiments with mixed early and late passage cells. The introduction of fluid flow through the device can further increase the fraction of highly motile stem cells, improving the assay's effectiveness to remove senescent hMSCs.</p><h3 data-test=\\\"abstract-sub-heading\\\">Conclusions</h3><p>Collectively, this assay facilitates the detection and isolation of a highly potent stem cell subpopulation. 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引用次数: 0
摘要
目的 人类间充质干细胞(hMSCs)的临床表现不尽如人意,引发了人们对其治疗潜力的担忧。造成这一问题的一个主要因素是间充质干细胞的异质性。干细胞扩增过程中衰老细胞的积累是间充质干细胞异质性的主要驱动因素。目前根除衰老hMSCs的方法要么成功率有限,要么缺乏临床意义。本研究利用hMSCs向受损组织迁移的固有能力,作为辨别衰老干细胞和新生干细胞的一种方法。鉴于衰老细胞缺乏在生理相关环境中迁移的能力,我们假设一个微流体装置可作为识别衰老细胞的平台,该装置旨在模拟体内细胞运动的关键环节。结果与非迁移性细胞相比,该装置检测到的高迁移性 hMSCs 不仅速度更快、体积更小、增殖能力更强,而且 DNA 损伤和衰老程度也有所降低。此外,这种检测方法还能在混合早期和晚期细胞的实验中检测到衰老前的细胞。通过该装置引入液流可进一步增加高运动性干细胞的比例,从而提高该检测方法去除衰老hMSCs的效果。鉴于给药间充质干细胞的迁移潜能与长期临床疗效之间存在正相关,提供均一、高运动性的衰老前hMSCs可能有利于患者的疗效。
Leveraging Cell Migration Dynamics to Discriminate Between Senescent and Presenescent Human Mesenchymal Stem Cells
Purpose
The suboptimal clinical performance of human mesenchymal stem cells (hMSCs) has raised concerns about their therapeutic potential. One major contributing factor to this issue is the heterogeneous nature of hMSCs. Senescent cell accumulation during stem cell expansion is a key driver of MSC heterogeneity. Current methodologies to eradicate senescent hMSCs have either shown limited success or lack clinical relevance. This study leverages the inherent capacity of hMSCs to migrate toward damaged tissues as a means to discern senescent from presenescent stem cells. Given the established deficiency of senescent cells to migrate through physiologically relevant environments, we hypothesized that a microfluidic device, designed to emulate key facets of in vivo cell motility, could serve as a platform for identifying presenescent cells.
Methods
We employed a Y-shaped microchannel assay, which allows fine-tuning of fluid flow rates and the degree of confinement.
Results
Highly migratory hMSCs detected by the device not only demonstrate increased speed, smaller size, and higher proliferative capacity but also manifest reduced DNA damage and senescence compared to non-migratory cells. Additionally, this assay detects presenescent cells in experiments with mixed early and late passage cells. The introduction of fluid flow through the device can further increase the fraction of highly motile stem cells, improving the assay's effectiveness to remove senescent hMSCs.
Conclusions
Collectively, this assay facilitates the detection and isolation of a highly potent stem cell subpopulation. Given the positive correlation between the migratory potential of administered MSCs and the long-term clinical outcome, delivering homogeneous, highly motile presenescent hMSCs may benefit patient outcomes.
期刊介绍:
The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas:
Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example.
Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions.
Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress.
Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.