Facchin Federica, Canaider Silvia, Bianconi Eva, Maioli Margherita, Santoro Umberto, Santaniello Sara, Basoli Valentina, Biava Pier Mario, Ventura Carlo
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy.
Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.
Front Biosci (Schol Ed). 2019 Mar 1;11(1):89-104. doi: 10.2741/S528.
Human adult stem cells hold promise for regenerative medicine. They are usually expanded for multiple passages to increase cell yield prior to transplantation. Unfortunately, prolonged culture leads to cell senescence, a major drawback from successful outcomes in cell therapy approaches. Here, we show that an extract from early Zebrafish embryo (ZF1) counteracted senescence progression in human adipose-derived stem cells (hASCs) along multiple culture passages (from the 5th to the 20th). Exposure to ZF1 strongly reduced the expression of senescence marker beta-galactosidase. Both stemness (, , and ) and anti-senescence (, and telomerase reverse transcriptase - ) related genes were overexpressed at specific experimental points, without recruitment of the cyclin-dependent kinase Inhibitor 2A (, ali-as ). Increased telomerase activity was associatt-ed with overexpression. Both osteogenic and adipogenic abilities were enhanced. In conclusion, hASCs exposure to ZF1 is a feasible tool to counteract and reverse human stem cell senescence in long-term culturing conditions.
人类成体干细胞为再生医学带来了希望。在移植前,它们通常会经过多次传代扩增以提高细胞产量。不幸的是,长时间培养会导致细胞衰老,这是细胞治疗方法取得成功的一个主要障碍。在此,我们表明,早期斑马鱼胚胎提取物(ZF1)可在多代培养过程中(从第5代到第20代)抵消人类脂肪来源干细胞(hASC)的衰老进程。暴露于ZF1可显著降低衰老标志物β-半乳糖苷酶的表达。在特定实验点,干性相关基因(Oct4、Sox2和Nanog)和抗衰老相关基因(p16、p21和端粒酶逆转录酶TERT)均有过表达,而细胞周期蛋白依赖性激酶抑制剂2A(p16,别名CDKN2A)未被募集。端粒酶活性增加与TERT过表达相关。成骨和成脂能力均得到增强。总之,在长期培养条件下,hASC暴露于ZF1是抵消和逆转人类干细胞衰老的一种可行方法。