Antisenescence effect of mouse embryonic stem cell conditioned medium through a PDGF/FGF pathway

被引:31
作者
Bae, Yun-Ui [1 ,2 ]
Choi, Joon-Hyuk [3 ]
Nagy, Andras [4 ]
Sung, Hoon-Ki [4 ,5 ]
Kim, Jae-Ryong [1 ,2 ]
机构
[1] Yeungnam Univ, Coll Med, Dept Biochem & Mol Biol, 170 Hyunchung Ro, Daegu 705717, South Korea
[2] Yeungnam Univ, Coll Med, Smart Aging Convergence Res Ctr, Daegu 705717, South Korea
[3] Yeungnam Univ, Coll Med, Dept Pathol, Daegu 705717, South Korea
[4] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada
[5] Hosp Sick Children, Res Inst, Physiol & Expt Med Program, Toronto, ON M5G 0A4, Canada
基金
新加坡国家研究基金会;
关键词
cellular senescence; conditioned medium; embryonic stem cells; PDGF-BB; PLASMINOGEN-ACTIVATOR INHIBITOR-1; GROWTH-FACTOR BB; REPLICATIVE SENESCENCE; LIFE-SPAN; ENDOTHELIAL-CELLS; PROGENITOR CELLS; IN-VITRO; ANGIOGENESIS; MICE; FIBROBLASTS;
D O I
10.1096/fj.15-278846
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Cellular senescence, an irreversible state of growth arrest, underlies organismal aging and age-related diseases. Recent evidence suggests that aging intervention based on inhibition of cellular senescence might be a promising strategy for treatment of aging and age-related diseases. Embryonic stem cells (ESCs) and ESC conditioned medium (CM) have been suggested as a desirable source for regenerative medicine. However, effects of ESC-CM on cellular senescence remain to be determined. We found that treatment of senescent human dermal fibroblasts with CM from mouse ESCs (mESCs) decreases senescence phenotypes. We found that platelet-derived growth factor BB in mESC-CM plays a critical role in antisenescence effect of mESC-CM through up-regulation of fibroblast growth factor 2. We confirmed that mESC-CM treatment accelerates the wound-healing process by down-regulating senescence-associated p53 expression in in vivo models. Taken together, our results suggest that mESC-CM has the ability to suppress cellular senescence and maintain proliferative capacity. Therefore, this strategy might emerge as a novel therapeutic strategy for aging and age-related diseases.
引用
收藏
页码:1276 / 1286
页数:11
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