title: Antisenescence effect of mouse embryonic stem cell conditioned medium through a PDGF/FGF pathway.
abstract: 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.
authors.affiliation: *Department of Biochemistry and Molecular Biology, Smart-Aging Convergence Research Center, and Department of Pathology, College of Medicine, Yeungnam University, Daegu, Republic of Korea; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; and Physiology and Experimental Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
authors.forename: Yun-Ui
authors.initials: YU
authors.lastname: Bae
authors.affiliation: *Department of Biochemistry and Molecular Biology, Smart-Aging Convergence Research Center, and Department of Pathology, College of Medicine, Yeungnam University, Daegu, Republic of Korea; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; and Physiology and Experimental Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
authors.forename: Joon-Hyuk
authors.initials: JH
authors.lastname: Choi
authors.affiliation: *Department of Biochemistry and Molecular Biology, Smart-Aging Convergence Research Center, and Department of Pathology, College of Medicine, Yeungnam University, Daegu, Republic of Korea; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; and Physiology and Experimental Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
authors.forename: Andras
authors.initials: A
authors.lastname: Nagy
authors.affiliation: *Department of Biochemistry and Molecular Biology, Smart-Aging Convergence Research Center, and Department of Pathology, College of Medicine, Yeungnam University, Daegu, Republic of Korea; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; and Physiology and Experimental Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada hoon-ki.sung@sickkids.ca kimjr@ynu.ac.kr.
authors.forename: Hoon-Ki
authors.initials: HK
authors.lastname: Sung
authors.affiliation: *Department of Biochemistry and Molecular Biology, Smart-Aging Convergence Research Center, and Department of Pathology, College of Medicine, Yeungnam University, Daegu, Republic of Korea; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; and Physiology and Experimental Medicine Program, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada hoon-ki.sung@sickkids.ca kimjr@ynu.ac.kr.
authors.forename: Jae-Ryong
authors.initials: JR
authors.lastname: Kim
mesh_terms: D000818:Animals; D000077214:Becaplermin; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D017077:Culture Media, Conditioned; D020574:Proto-Oncogene Proteins c-sis; D016159:Tumor Suppressor Protein p53; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin
keywords: PDGF-BB; cellular senescence; conditioned medium; embryonic stem cells