Cai Jingyi, Qi Hexu, Yao Ke, Yao Yang, Jing Dian, Liao Wen, Zhao Zhihe
State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Front Cell Dev Biol. 2021 Mar 19;9:650431. doi: 10.3389/fcell.2021.650431. eCollection 2021.
The thirst to postpone and even reverse aging progress has never been quenched after all these decades. Unequivocally, mesenchymal stem cells (MSCs), with extraordinary abilities such as self-renewal and multi-directional differentiation, deserve the limelight in this topic. Though having several affable clinical traits, MSCs going through senescence would, on one hand, contribute to age-related diseases and, on the other hand, lead to compromised or even counterproductive therapeutical outcomes. Notably, increasing evidence suggests that non-coding RNAs (ncRNAs) could invigorate various regulatory processes. With even a slight dip or an uptick of expression, ncRNAs would make a dent in or even overturn cellular fate. Thereby, a systematic illustration of ncRNAs identified so far to steer MSCs during senescence is axiomatically an urgent need. In this review, we introduce the general properties and mechanisms of senescence and its relationship with MSCs and illustrate the ncRNAs playing a role in the cellular senescence of MSCs. It is then followed by the elucidation of ncRNAs embodied in extracellular vesicles connecting senescent MSCs with other cells and diversified processes in and beyond the skeletal system. Last, we provide a glimpse into the clinical methodologies of ncRNA-based therapies in MSC-related fields. Hopefully, the intricate relationship between senescence and MSCs will be revealed one day and our work could be a crucial stepping-stone toward that future.
几十年来，推迟甚至逆转衰老进程的渴望从未平息。毫无疑问，间充质干细胞（MSCs）具有自我更新和多向分化等非凡能力，理应在这个话题中备受关注。尽管MSCs具有一些良好的临床特性，但经历衰老的MSCs一方面会导致与年龄相关的疾病，另一方面会导致治疗效果受损甚至适得其反。值得注意的是，越来越多的证据表明，非编码RNA（ncRNAs）可以促进各种调节过程。即使ncRNAs的表达略有下降或上升，也会对细胞命运产生影响甚至彻底改变。因此，对目前已确定的在衰老过程中调控MSCs的ncRNAs进行系统阐述显然是迫切需要的。在这篇综述中，我们介绍了衰老的一般特性和机制及其与MSCs的关系，并阐述了在MSCs细胞衰老中起作用的ncRNAs。随后阐明了细胞外囊泡中包含的ncRNAs，这些ncRNAs将衰老的MSCs与其他细胞以及骨骼系统内外的多种过程联系起来。最后，我们简要介绍了基于ncRNA的疗法在MSCs相关领域的临床方法。希望有一天衰老与MSCs之间的复杂关系能够被揭示，而我们的工作可能是迈向未来的关键一步。
