Senescence-associated secretory phenotypes in rat-derived dedifferentiated fat cells with replicative senescence

• Published in: Dental Materials Journal Vol. 42; no. 3; pp. 351 - 359
• Main Authors: DENG, Wenqi, JO, Jun-ichiro, MORIKUNI, Hidetoshi, SASAYAMA, Satoshi, HASHIMOTO, Yoshiya, MATSUMOTO, Naoyuki, HONDA, Yoshitomo
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Society for Dental Materials and Devices 25-05-2023; Japan Science and Technology Agency
• Subjects: Adipocytes; Cell culture; Cell size; Cellular senescence; CXCL12 protein; Dedifferentiated fat cell; Inflammation; Interleukin 1; Interleukin 11; Interleukin 13; Phenotypes; Regenerative medicine; Senescence; Senescence-associated secretory phenotypes; Tissue engineering; Dedifferentiated fat cell; Senescence-associated secretory phenotypes; Cellular senescence
• ISSN: 0287-4547; 1881-1361
• DOI: 10.4012/dmj.2022-242

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, RT2 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.