Senescence-associated ultrastructural features of long-term cultures of induced pluripotent stem cells (iPSCs)

Fiorella Colasuonno, Rossella Borghi, Alessia Niceforo, Maurizio Muzzi, Enrico Bertini, Andrea Di Giulio, Sandra Moreno, Claudia Compagnucci

Research output: Contribution to journalArticlepeer-review

Abstract

Induced pluripotent stem cells (iPSCs) hold great promise for developing personalized regenerative medicine, however characterization of their biological features is still incomplete. Moreover, changes occurring in longterm cultured iPSCs have been reported, suggesting these as a model of cellular aging. For this reason, we addressed the ultrastructural characterization of iPSCs, with a focus on possible time-dependent changes, involving specific cell compartments. To this aim, we comparatively analysed cultures at different timepoints, by an innovative electron microscopic technology (FIB/SEM). We observed progressive loss of cell-to-cell contacts, associated with increased occurrence of exosomes. Mitochondria gradually increased, while acquiring an elongated shape, with well-developed cristae. Such mitochondrial maturation was accompanied by their turnover, as assessed by the presence of autophagomes (undetectable in young iPSCs), some containing recognizable mitochondria. This finding was especially frequent in middle-aged iPSCs, while being occasional in aged cells, suggesting early autophagic activation followed by a decreased efficiency of the process with culturing time. Accordingly, confocal microscopy showed age-dependent alterations to the expression and distribution of autophagic markers. Interestingly, responsivity to rapamycin, highest in young iPSCs, was almost lost in aged cells. Overall, our results strongly support long-term cultured iPSCs as a model for studying relevant aspects of cellular senescence, involving intercellular communication, energy metabolism, and autophagy.

Original languageEnglish
Pages (from-to)2206-2219
Number of pages14
JournalAging
Volume9
Issue number10
DOIs
Publication statusPublished - Jan 1 2017

Keywords

  • Aging
  • Autophagy
  • Cell-cell contacts
  • FIB/SEM
  • IPSCs
  • Mitochondria

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

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