Adult stem cell maintenance and tissue regeneration around the clock: do impaired stem cell clocks drive age-associated tissue degeneration?
Adult stem cell maintenance and tissue regeneration around the clock: do impaired stem cell clocks drive age-associated tissue degeneration?
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DOI：
10.1007/s10522-018-9772-6
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发表时间：
2018-12
期刊：
影响因子：
4.5
通讯作者：
Pekovic-Vaughan V
中科院分区：
文献类型：
--
作者：
Rogers EH;Hunt JA;Pekovic-Vaughan V
人类成体干细胞研究是现代组织工程中一个非常多产的领域，因为这些细胞具有为世界上日益老龄化的人口提供未来细胞疗法的巨大潜力。细胞疗法需要一种智能生物材料来输送和定位细胞群;保护和引导干细胞进入预定的谱系特异性途径。反过来，细胞可以为生物材料提供保护并延长其寿命。干细胞和生物材料的正确组合可以显着提高治疗效果。成体干细胞被用于靶向许多随着年龄增长而对组织功能产生负面影响的变化。了解导致衰老过程所带来的变化的潜在机制是必要的，因为衰老会对干细胞的激活，维持和分化产生许多不利影响。昼夜节律钟是一种进化上保守的计时机制，其将生理、代谢和行为与24小时太阳日协调，以提供与外部环境的时间组织内稳态。昼夜节律在行为和分子水平上随着年龄的增长而恶化，导致人类和啮齿动物模型中下游节律组织生理学的年龄相关变化。在这篇综述中，我们强调了最近的进展，在我们的知识的作用，昼夜节律钟在成体干细胞的维护，由细胞自主和组织特异性因素驱动，以及他们的机制，他们增选各种细胞信号转导通路施加时间控制干细胞功能。未来的研究调查药理学和生活方式的干预，其中昼夜节律成人干壁龛内可以被操纵将提供途径的时间引导的细胞疗法和智能生物材料，以改善与年龄相关的组织退化和减少慢性疾病的负担。
Human adult stem cell research is a highly prolific area in modern tissue engineering as these cells have significant potential to provide future cellular therapies for the world’s increasingly aged population. Cellular therapies require a smart biomaterial to deliver and localise the cell population; protecting and guiding the stem cells toward predetermined lineage-specific pathways. The cells, in turn, can provide protection to biomaterials and increase its longevity. The right combination of stem cells and biomaterials can significantly increase the therapeutic efficacy. Adult stem cells are utilised to target many changes that negatively impact tissue functions with age. Understanding the underlying mechanisms that lead to changes brought about by the ageing process is imperative as ageing leads to many detrimental effects on stem cell activation, maintenance and differentiation. The circadian clock is an evolutionarily conserved timing mechanism that coordinates physiology, metabolism and behavior with the 24 h solar day to provide temporal tissue homeostasis with the external environment. Circadian rhythms deteriorate with age at both the behavioural and molecular levels, leading to age-associated changes in downstream rhythmic tissue physiology in humans and rodent models. In this review, we highlight recent advances in our knowledge of the role of circadian clocks in adult stem cell maintenance, driven by both cell-autonomous and tissue-specific factors, and the mechanisms by which they co-opt various cellular signaling pathways to impose temporal control on stem cell function. Future research investigating pharmacological and lifestyle interventions by which circadian rhythms within adult stem niches can be manipulated will provide avenues for temporally guided cellular therapies and smart biomaterials to ameliorate age-related tissue deterioration and reduce the burden of chronic disease.
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