title: Characterization of Senescence of Culture-expanded Human Adipose-derived Mesenchymal Stem Cells.
abstract: OBJECTIVE
  Adipose-derived mesenchymal stem cells (ADSCs) are promising candidates in regenerative medicine. The need for in vitro propagation to obtain therapeutic quantities of the cells imposes a risk of impaired functionality due to cellular senescence. The aim of the study was to analyze in vitro senescence of previously cryopreserved human ADSCs subjected to serial passages in cell culture.
  
  
  RESULTS
  ADSC cultures from 8 donors were cultivated until proliferation arrest was reached. A gradual decline of ADSC fitness was observed by altered cell morphology, loss of proliferative, clonogenic and differentiation abilities and increased β-galactosidase expression all of which occurred in a donor-specific manner. Relative telomere length (RTL) analysis revealed that only three tested cultures encountered replicative senescence. The presence of two ADSC subsets with significantly different RTL and cell size was discovered. The heterogeneity of ADSC cultures was supported by the intermittent nature of aging seen in tested samples.
  
  
  CONCLUSIONS
  We conclude that the onset of in vitro senescence of ADSCs is a strongly donor-specific process which is complicated by the intricate dynamics of cell subsets present in ADSC population. This complexity needs to be carefully considered when elaborating protocols for personalized cellular therapy.
authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia.
authors.forename: Diana
authors.initials: D
authors.lastname: Legzdina
authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia.
authors.forename: Anete
authors.initials: A
authors.lastname: Romanauska
authors.affiliation: Children's Clinical University Hospital, Clinical Laboratory, Riga, Latvia.
authors.forename: Sergey
authors.initials: S
authors.lastname: Nikulshin
authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Kozlovska
authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia.
authors.forename: Uldis
authors.initials: U
authors.lastname: Berzins
keywords: Cell aging; Heterogeneity; Human adipose-derived mesenchymal stem cells; Relative telomere length; Serial passage; Subpopulations