首页 | 本学科首页   官方微博 | 高级检索  
     


Identification of senescent cells in multipotent mesenchymal stromal cell cultures: Current methods and future directions
Authors:WEICHAO Zhai  DERRICK YONG  JEHAN JOMAA EL-JAWHARI  RICHARD CUTHBERT  DENNIS MCGONAGLE  MAY WIN NAING  ELENA JONES
Affiliation:1. Leeds Institute of Rheumatic and musculoskeletal Medicine, Leeds, UK;2. Singapore Institute of Manufacturing Technology, A*STAR, Innovis, Singapore;3. Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
Abstract:Regardless of their tissue of origin, multipotent mesenchymal stromal cells (MSCs) are commonly expanded in vitro for several population doublings to achieve a sufficient number of cells for therapy. Prolonged MSC expansion has been shown to result in phenotypical, morphological and gene expression changes in MSCs, which ultimately lead to the state of senescence. The presence of senescent cells in therapeutic MSC batches is undesirable because it reduces their viability, differentiation potential and trophic capabilities. Additionally, senescent cells acquire senescence-activated secretory phenotype, which may not only induce apoptosis in the neighboring host cells following MSC transplantation, but also trigger local inflammatory reactions. This review outlines the current and promising new methodologies for the identification of senescent cells in MSC cultures, with a particular emphasis on non-destructive and label-free methodologies. Technologies allowing identification of individual senescent cells, based on new surface markers, offer potential advantage for targeted senescent cell removal using new-generation senolytic agents, and subsequent production of therapeutic MSC batches fully devoid of senescent cells. Methods or a combination of methods that are non-destructive and label-free, for example, involving cell size and spectroscopic measurements, could be the best way forward because they do not modify the cells of interest, thus maximizing the final output of therapeutic-grade MSC cultures. The further incorporation of machine learning methods has also recently shown promise in facilitating, automating and enhancing the analysis of these measured data.
Keywords:label-free  multipotent mesenchymal stromal cells  non-destructive  replicative aging  senescence
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号