Ratushnyy Andrey, Lobanova Margarita, Buravkova Ludmila B
Lab. of Cell Physiology, Institute of Biomedical Problems of Russian Academy of Science, Moscow, Russia.
Cell Biochem Funct. 2017 Jun;35(4):232-243. doi: 10.1002/cbf.3267.
Multipotent mesenchymal stromal cells are considered as a perspective tool in cell therapy and regenerative medicine. Unfortunately, autologous cell therapy does not always provide positive outcomes in elder donors, perhaps as a result of the alterations of stem cell compartments. The mechanisms of stem and progenitor cell senescence and the factors engaged are investigated intensively. In present paper, we elucidated the effects of tissue-related O on morphology, functions, and transcriptomic profile of adipose tissue-derived stromal cells (ASCs) in replicative senescence in vitro model. Replicatively senescent ASCs at ambient (20%) O (12-21 passages) demonstrated an increased average cell size, granularity, reactive oxygen species level, including anion superoxide, lysosomal compartment activity, and IL-6 production. Decreased ASC viability and proliferation, as well as the change of more than 10 senescence-associated gene expression were detected (IGF1, CDKN1C, ID1, CCND1, etc). Long-term ASC expansion at low O (5%) revoked in part the replicative senescence-associated alterations.
多能间充质基质细胞被认为是细胞治疗和再生医学中的一种有前景的工具。不幸的是，自体细胞治疗在老年供体中并不总是能产生积极的效果，这可能是干细胞区室改变的结果。人们对干细胞和祖细胞衰老的机制以及相关因素进行了深入研究。在本文中，我们阐明了组织相关氧对体外复制性衰老模型中脂肪组织来源的基质细胞（ASC）的形态、功能和转录组谱的影响。在环境氧（20%）下处于复制性衰老的ASC（传代12 - 21次）表现出平均细胞大小增加、颗粒度增加、活性氧水平升高，包括超氧阴离子、溶酶体区室活性和白细胞介素 - 6产生增加。检测到ASC活力和增殖下降，以及超过10种衰老相关基因表达的变化（IGF1、CDKN1C、ID1、CCND1等）。在低氧（5%）条件下长期扩增ASC部分逆转了与复制性衰老相关的改变。
