Chitosan Treatment Delays the Induction of Senescence in Human Foreskin Fibroblast Strains

• Published in: PloS one 2015-10, Vol.10 (10), p.e0140747-e0140747
• Main Authors: Tsai, Ching-Wen, Kao, Yu-Ting, Chiang, I-Ni, Wang, Jyh-Horng, Young, Tai-Horng
• Format: Article
• Language: English
• Subjects: Aging; Apoptosis; Biomaterials; Biomedical engineering; Biomedical materials; Bone surgery; Cancer; CD3 antigen; Cell aging; Cell culture; Cell Cycle - drug effects; Cell Movement - drug effects; Cell size; Cell Survival - drug effects; Cells, Cultured; Cellular Senescence - drug effects; Cellular Senescence - genetics; Chitin; Chitosan; Chitosan - pharmacology; Engineering schools; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Foreskin - cytology; Foreskin - metabolism; Galactosidase; Gene Expression; Hospitals; Humans; Male; Markers; Medicine; p53 Protein; Physiological aspects; Polystyrene; Polystyrene resins; Prevention; Proteins; Retina; Retinoblastoma; Senescence; Spheroids; Tissue culture; Tissue engineering; Tumorigenesis; β-Galactosidase
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0140747

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.