Characterization of senescence of culture-expanded human adipose-derived mesenchymal stem cells

Diana Legzdina (Corresponding Author), Anete Romanauska, Sergey Nikulshin, Tatjana Kozlovska, Uldis Berzins

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)
20 Downloads (Pure)

Abstract

Background and Objectives: 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. Methods and 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.

Original languageEnglish
Pages (from-to)124-136
Number of pages13
JournalInternational Journal of Stem Cells
Volume9
Issue number1
DOIs
Publication statusPublished - 2016
Externally publishedYes

Keywords*

  • Cell aging
  • Heterogeneity
  • Human adipose-derived mesenchymal stem cells
  • Relative telomere length
  • Serial passage
  • Subpopulations

Field of Science*

  • 3.1 Basic medicine
  • 3.2 Clinical medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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