Department of Orthodontics, Osaka Dental University.
Department of Biomaterials, Osaka Dental University.
Dent Mater J. 2023 May 30;42(3):351-359. doi: 10.4012/dmj.2022-242. Epub 2023 Feb 10.
Senescence-associated secretory phenotype (SASPs) secreted from senescent cells often cause the deleterious damages to the surrounding tissues. Although dedifferentiated fat (DFAT) cells prepared are considered a promising cell source for regenerative therapies, SASPs from DFAT cells undergoing long-term cell culture, which latently induce replicative senescence, have barely been explored. The present study was designed to investigate senescent behaviors in rat-derived DFAT cells at high passage numbers and to analyze the possible types of SASPs. Our data show that DFAT cells undergo senescence during replicative passaging, as determined by multiple senescent hallmarks including morphological changes in cell shape and nucleus. Moreover, RT PCR array analysis indicated that senescent DFAT cells expressed higher levels of 16 inflammatory cytokines (Ccl11, Ccl12, Ccl21, Ccl5, Csf2, Cxcl1, Cxcl12, Ifna2, IL11, IL12a, IL13, IL1a, IL1rn, IL6, Mif, and Tnf) associated with SASPs than non-senescent cells. This study implicates that rat DFAT cells undergo cellular senescence after long-term cell culture; cautious consideration should be paid to treat SASP secretion when senescent DFAT cells are used in regenerative medicine.
衰老相关分泌表型（SASPs）由衰老细胞分泌，常导致周围组织的有害损伤。虽然去分化脂肪（DFAT）细胞被认为是再生治疗有前途的细胞来源，但来自经历长期细胞培养的 DFAT 细胞的 SASPs，潜伏诱导复制性衰老，几乎没有被探索过。本研究旨在研究高传代数大鼠来源的 DFAT 细胞中的衰老行为，并分析可能的 SASPs 类型。我们的数据表明，DFAT 细胞在复制传代过程中经历衰老，这是通过细胞形态和核的多种衰老标志来确定的。此外，RT-PCR 阵列分析表明，衰老的 DFAT 细胞表达更高水平的 16 种炎症细胞因子（Ccl11、Ccl12、Ccl21、Ccl5、Csf2、Cxcl1、Cxcl12、Ifna2、IL11、IL12a、IL13、IL1a、IL1rn、IL6、Mif 和 TNF）与 SASPs 相关，而非衰老细胞。本研究表明，大鼠 DFAT 细胞在长期细胞培养后经历细胞衰老；在再生医学中使用衰老的 DFAT 细胞时，应谨慎考虑 SASP 分泌的问题。
