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首页> 外文期刊>Journal of tissue engineering and regenerative medicine >Influence of in vitro biomimicked stem cell 'niche' for regulation of proliferation and differentiation of human bone marrow-derived mesenchymal stem cells to myocardial phenotypes: serum starvation without aid of chemical agents and prevention of spontaneous stem cell transformation enhanced by the matrix environment
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Influence of in vitro biomimicked stem cell 'niche' for regulation of proliferation and differentiation of human bone marrow-derived mesenchymal stem cells to myocardial phenotypes: serum starvation without aid of chemical agents and prevention of spontaneous stem cell transformation enhanced by the matrix environment

机译：体外仿生干细胞“小生境”对人骨髓间充质干细胞增殖和分化对心肌表型的调节的影响：无需化学试剂的血清饥饿和基质环境促进的自发性干细胞转化

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Niche appears important for preventing the spontaneous differentiation or senescence that cells undergo during in vitro expansion. In the present study, it was revealed that human bone marrow-derived mesenchymal stem cells (hBM-MSCs) undergo senescence-related differentiation into the myocardial lineage in vitro without any induction treatment. This phenomenon occurred over the whole population of MCSs, much different from conventional differentiation with limited frequency of occurrence, and was accompanied by a change of morphology into large, flat cells with impeded proliferation, which are the representative indications of MSC senescence. By culturing MSCs under several culture conditions, it was determined that induction treatment with 5-azacytidine was not associated with the phenomenon, but the serum-starvation condition, under which proliferation is severely hampered, caused senescence progression and upregulation of cardiac markers. Nevertheless, MSCs gradually developed a myocardial phenotype under normal culture conditions over a prolonged culture period and heterogeneous populations were formed. In perspectives of clinical applications, this must be prevented for fair and consistent outcomes. Hence, the biomimetic 'niche' was constituted for hBM-MSCs by cultivating on a conventionally available extracellular matrix (ECM). Consequently, cells on ECM regained a spindle-shape morphology, increased in proliferation rate by two-fold and showed decreased expression of cardiac markers at both the mRNA and protein levels. In conclusion, the outcome indicates that progression of MSC senescence may occur via myocardial differentiation during in vitro polystyrene culture, and this can be overcome by employing appropriate ECM culture techniques. Copyright (c) 2013 John Wiley & Sons, Ltd.
机译：生态位对于防止细胞在体外扩增过程中自发分化或衰老显得很重要。在本研究中，揭示了未经任何诱导处理的人骨髓间充质干细胞（hBM-MSC）在体外经历了与衰老相关的分化为心肌谱系。这种现象发生在整个MCS群体中，与常规分化相异，发生频率有限，并且伴随着形态学的改变，变成了大型的扁平细胞，阻止了增殖，这是MSC衰老的代表。通过在几种培养条件下培养MSC，可以确定5-氮杂胞苷的诱导处理与该现象无关，但是血清饥饿状态（严重抑制了增殖）导致衰老进程和心脏标志物上调。然而，MSC在正常培养条件下在延长的培养期内逐渐形成心肌表型，并形成了异质群体。从临床应用的角度来看，必须避免这种情况以取得公正一致的结果。因此，通过在常规可得的细胞外基质（ECM）上培养，为hBM-MSC构建了仿生“小生境”。因此，ECM上的细胞恢复了纺锤形的形态，增殖速率提高了两倍，并且在mRNA和蛋白质水平上均显示出心脏标志物的表达降低。总之，结果表明，在体外聚苯乙烯培养过程中，心肌分化可能通过心肌分化而发生，这可以通过采用适当的ECM培养技术来克服。版权所有（c）2013 John Wiley＆Sons，Ltd.

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