Cellular expansion of MSCs: Shifting the regenerative potential.
Cellular expansion of MSCs: Shifting the regenerative potential.
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间充质来源的基质细胞或祖细胞，通常被称为“MSCs”，因其促进组织再生和减少炎症的显着能力而引起了显著的临床兴趣。最近的研究表明，MSCs的治疗作用最初归因于细胞向目标组织的直接分化能力，在很大程度上是由细胞分泌的生物分子驱动的，包括细胞因子、趋化因子、生长因子和含有miRNA的细胞外囊泡。该分泌组通过MSCs与宿主组织细胞的串扰协调局部微环境中内源性修复和免疫调节的上调。骨髓间充质干细胞及其分泌组衍生产品的治疗应用通常涉及体外单层扩增。然而，连续传代MSCs显著改变其治疗潜力，诱导从促再生表型向促炎症表型的广泛转变。MSCs体外扩增的一个一致的副产物是复制性衰老的开始，这是一种以促炎细胞因子和生长因子释放增加为特征的细胞停滞状态。然而，对体外扩增不同阶段分泌组谱的变化知之甚少。一些培养条件和生物处理技术已经显示出在整个增殖过程中更有效地保持促再生和抗炎症间充质干细胞表型的希望。了解体外扩增条件如何影响MSCs的性质和功能，以及它们相关的分泌组，可能为驱动这些改变的潜在机制提供关键见解。阐明MSC分泌组在体外扩增的每个阶段的动态和多样化变化是开发标准化、安全和有效的基于MSC的治疗方法的关键一步。在体外扩增过程中，MSCs及其分泌组经历了从促再生表型到促炎症表型的转变。这种转变背后的变化包括DNA甲基化谱的改变、形态异常、端粒缩短、氧化应激、衰老和分泌的生物分子（细胞因子、趋化因子、生长因子、MSC - ev）。保留培养扩增MSCs功能特性的方法包括细胞预处理（缺氧、炎症细胞因子、3D培养）、药物干预（抗衰老药物）和端粒酶过表达。
Mesenchymal‐derived stromal or progenitor cells, commonly called “MSCs,” have attracted significant clinical interest for their remarkable abilities to promote tissue regeneration and reduce inflammation. Recent studies have shown that MSCs' therapeutic effects, originally attributed to the cells' direct differentiation capacity into the tissue of interest, are largely driven by the biomolecules the cells secrete, including cytokines, chemokines, growth factors, and extracellular vesicles containing miRNA. This secretome coordinates upregulation of endogenous repair and immunomodulation in the local microenvironment through crosstalk of MSCs with host tissue cells. Therapeutic applications for MSCs and their secretome‐derived products often involve in vitro monolayer expansion. However, consecutive passaging of MSCs significantly alters their therapeutic potential, inducing a broad shift from a pro‐regenerative to a pro‐inflammatory phenotype. A consistent by‐product of in vitro expansion of MSCs is the onset of replicative senescence, a state of cell arrest characterized by an increased release of proinflammatory cytokines and growth factors. However, little is known about changes in the secretome profile at different stages of in vitro expansion. Some culture conditions and bioprocessing techniques have shown promise in more effectively retaining the pro‐regenerative and anti‐inflammatory MSC phenotype throughout expansion. Understanding how in vitro expansion conditions influence the nature and function of MSCs, and their associated secretome, may provide key insights into the underlying mechanisms driving these alterations. Elucidating the dynamic and diverse changes in the MSC secretome at each stage of in vitro expansion is a critical next step in the development of standardized, safe, and effective MSC‐based therapies. Throughout in vitro expansion, MSCs and their secretome undergo a shift from a pro‐regenerative to a proinflammatory phenotype. Changes underlying this shift include alterations in DNA methylation profile, morphological abnormalities, telomere shortening, oxidative stress, senescence, and secreted biomolecules (cytokines, chemokines, growth factors, MSC‐EVs). Approaches that have shown promise in retaining the functional properties of culture‐expanded MSCs include cellular preconditioning (hypoxia, inflammatory cytokines, 3D culturing), pharmacological interventions (senolytics), and telomerase overexpression.
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影响因子：
7.5
作者：
Almeria, Ciarra;Kress, Sebastian;Weber, Viktoria;Egger, Dominik;Kasper, Cornelia
通讯作者：
Kasper, Cornelia
DOI：
10.1042/bcj20190382
发表时间：
2020-09-18
期刊：
The Biochemical journal
影响因子：
--
作者：
Childs PG;Reid S;Salmeron-Sanchez M;Dalby MJ
通讯作者：
Dalby MJ
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
4.6
作者：
Dong LH;Jiang YY;Liu YJ;Cui S;Xia CC;Qu C;Jiang X;Qu YQ;Chang PY;Liu F
通讯作者：
Liu F
影响因子：
2.6
作者：
Bartholomew, A;Sturgeon, C;Hoffman, R
通讯作者：
Hoffman, R