title: Chitosan Treatment Delays the Induction of Senescence in Human Foreskin Fibroblast Strains.
abstract: Fibroblasts have been extensively used as a model to study cellular senescence. The purpose of this study was to investigate whether the human foreskin fibroblast aging process could be regulated by using the biomaterial chitosan. Fibroblasts cultured on commercial tissue culture polystyrene (TCPS) entered senescence after 55-60 population doublings (PDs), and were accompanied by larger cell shape, higher senescence-associated β-galactosidase (SA β-gal) activity, lower proliferation capacity, and upregulation of senescence-associated molecular markers p21, p53, retinoblastoma (pRB), and p16. Before senescence was reached, PD48 cells were collected from TCPS and seeded on chitosan for three days (PD48-Cd3) to form multicellular spheroids. The protein expression of senescence-associated secretory phenotypes (SASPs) and senescence-associated molecular markers of these cells in PD48-Cd3 spheroids were downregulated significantly. Following chitosan treatment, fibroblasts reseeded on TCPS showed lower SA β-gal activity, increased cellular motility, and a higher proliferation ability of 70-75 PDs. These phenotypic changes were not accompanied by colonies forming in soft agar and a continuous decrease in the senescence-associated proteins p53 and pRB which act as a barrier to tumorigenesis. These results demonstrate that chitosan treatment could delay the induction of senescence which may be useful and safe for future tissue engineering applications.
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei 100, Taiwan, No.1, Sec. 1, Jen - Ai Rd., Taipei 100, Taiwan.
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Tsai
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei 100, Taiwan, No.1, Sec. 1, Jen - Ai Rd., Taipei 100, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Kao
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei 100, Taiwan, No.1, Sec. 1, Jen - Ai Rd., Taipei 100, Taiwan; Department of Urology, National Taiwan University Hospital, Taipei 100, Taiwan, No.7, Chung-Shan S. Rd., Taipei 100, Taiwan.
authors.forename: I-Ni
authors.initials: IN
authors.lastname: Chiang
authors.affiliation: Department of Orthopedic Surgery, National Taiwan University Hospital, Taipei 100, Taiwan, No.7, Chung-Shan S. Rd., Taipei 100, Taiwan.
authors.forename: Jyh-Horng
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei 100, Taiwan, No.1, Sec. 1, Jen - Ai Rd., Taipei 100, Taiwan.
authors.forename: Tai-Horng
authors.initials: TH
authors.lastname: Young
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects* / Q000235:genetics; D048271:Chitosan / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D052816:Foreskin / Q000166:cytology* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008297:Male
chemical_list: D048271:Chitosan