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Prolonged hypoxia delays aging and preserves functionality of human amniotic fluid stem cells.
Mechanisms of Ageing and Development ( IF 5.3 ) Pub Date : 2020-08-13 , DOI: 10.1016/j.mad.2020.111328
Francesca Casciaro 1 , Michela Borghesan 2 , Francesca Beretti 3 , Manuela Zavatti 3 , Emma Bertucci 4 , Matilde Yung Follo 5 , Tullia Maraldi 3 , Marco Demaria 2
Affiliation  

Human amniotic fluid stem cells (hAFSCs) are an emerging tool in regenerative medicine because they have the ability to differentiate into various lineages and efficiently improve tissue regeneration with no risk of tumorigenesis. Although hAFSCs are easily isolated from the amniotic fluid, their expansion ex vivo is limited by a quick exhaustion which impairs replicative potential and differentiation capacity. In this study, we evaluate various aging features of hAFSCs cultured at different oxygen concentrations. We show that low oxygen (1% O2) extends stemness and proliferative features, and delays induction of senescence-associated markers. Hypoxic hAFSCs activate a metabolic shift and increase resistance to pro-apoptotic stimuli. Moreover, we observe that cells at low oxygen remain capable of osteogenesis for prolonged periods of time, suggesting a more youthful phenotype. Together, these data demonstrate that low oxygen concentrations might improve the generation of functional hAFSCs for therapeutic use by delaying the onset of cellular aging.



中文翻译:

长期缺氧可延缓衰老并保持人类羊水干细胞的功能。

人类羊水干细胞 (hAFSCs) 是再生医学的新兴工具,因为它们能够分化成各种谱系并有效地促进组织再生,而没有肿瘤发生的风险。尽管 hAFSCs 很容易从羊水中分离出来,但它们的体外扩张受到快速衰竭的限制,这会损害复制潜力和分化能力。在这项研究中,我们评估了在不同氧浓度下培养的 hAFSCs 的各种老化特征。我们表明低氧 (1% O 2) 扩展干性和增殖特征,并延迟衰老相关标志物的诱导。缺氧 hAFSC 激活代谢转变并增加对促凋亡刺激的抵抗力。此外,我们观察到低氧条件下的细胞在很长一段时间内保持成骨能力,表明更年轻的表型。总之,这些数据表明,低氧浓度可能通过延迟细胞衰老的开始来改善用于治疗用途的功能性 hAFSC 的产生。

更新日期:2020-08-16
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