Functional comparison of chronological and in vitro aging: differential role of the cytoskeleton and mitochondria in mesenchymal stromal cells.
Functional comparison of chronological and in vitro aging: differential role of the cytoskeleton and mitochondria in mesenchymal stromal cells.
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DOI：
10.1371/journal.pone.0052700
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Duda GN
中科院分区：
文献类型：
--
作者：
Geissler S;Textor M;Kühnisch J;Könnig D;Klein O;Ode A;Pfitzner T;Adjaye J;Kasper G;Duda GN
间充质基质细胞（MSC）与间充质组织如骨和软骨的再生高度相关。MSC在基于细胞的治疗和组织工程中的有希望的作用似乎是有限的，这是由于其再生潜力随着供体年龄的增加而下降，其在人体组织中的可用性有限，以及在治疗前需要体外扩增。因此，我们的目的是确定在何种程度上在体外老化和时序老化可能是类似的过程，或者如果在体外培养相关的变化，在细胞和分子水平上至少改变作为供体年龄的函数。为此，我们建立了年轻（yMSC）和老年（aMSC）大鼠的MSC培养物，培养超过100代。这些长期MSC培养物是非致瘤性的，并且表现出与第2代的原代MSC相似的表面标志物模式。在体外扩增期间，但不是在时间老化期间，MSC逐渐失去其祖细胞特征，例如，成骨分化潜能完全丧失、成脂分化减少、细胞形态改变和衰老易感性增加。转录组分析显示，长期在体外培养的MSC导致下调的基因参与细胞分化，粘着斑组织，细胞骨架周转和线粒体功能。因此，功能分析表明在长期培养的yMSC以及aMSC中改变的线粒体形态、降低的抗氧化能力和升高的ROS水平。值得注意的是，只有MSC的迁移潜力和抗氧化能力在体外以及时序老化改变。根据观察到的时间和体外MSC老化的影响之间的具体差异，我们得出结论，两者都是不同的过程。
Mesenchymal stromal cells (MSCs) are of high relevance for the regeneration of mesenchymal tissues such as bone and cartilage. The promising role of MSCs in cell-based therapies and tissue engineering appears to be limited due to a decline of their regenerative potential with increasing donor age, their limited availability in human tissues and the need of in vitro expansion prior to treatment. We therefore aimed to determine to which degree in vitro aging and chronological aging may be similar processes or if in vitro culture-related changes at the cellular and molecular level are at least altered as a function of donor age. For that purpose we established MSCs cultures from young (yMSCs) and aged (aMSCs) rats that were cultured for more than 100 passages. These long-term MSCs cultures were non-tumorigenic and exhibited similar surface marker patterns as primary MSCs of passage 2. During in vitro expansion, but not during chronological aging, MSCs progressively lose their progenitor characteristics, e.g., complete loss of osteogenic differentiation potential, diminished adipogenic differentiation, altered cell morphology and increased susceptibility towards senescence. Transcriptome analysis revealed that long-term in vitro MSCs cultivation leads to down-regulation of genes involved in cell differentiation, focal adhesion organization, cytoskeleton turnover and mitochondria function. Accordingly, functional analysis demonstrated altered mitochondrial morphology, decreased antioxidant capacities and elevated ROS levels in long-term cultivated yMSCs as well as aMSCs. Notably, only the MSC migration potential and their antioxidative capacity were altered by in vitro as well as chronological aging. Based on specific differences observed between the impact of chronological and in vitro MSC aging we conclude that both are distinct processes.
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影响因子：
5.2
作者：
Kasper, Grit;Dankert, Niels;Duda, Georg N.
通讯作者：
Duda, Georg N.
影响因子：
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作者：
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11.8
作者：
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