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Senescence-associated ultrastructural features of long-term cultures of induced pluripotent stem cells (iPSCs).
- Source :
-
Aging [Aging (Albany NY)] 2017 Oct 23; Vol. 9 (10), pp. 2209-2222. - Publication Year :
- 2017
-
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 long-term 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.
Details
- Language :
- English
- ISSN :
- 1945-4589
- Volume :
- 9
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Aging
- Publication Type :
- Academic Journal
- Accession number :
- 29064821
- Full Text :
- https://doi.org/10.18632/aging.101309