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Senescence-associated ultrastructural features of long-term cultures of induced pluripotent stem cells (iPSCs)
- Source :
- Aging (Albany NY)
- Publication Year :
- 2017
- Publisher :
- Impact Journals LLC, 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.
- Subjects :
- 0301 basic medicine
Senescence
Adult
Male
autophagy
Induced Pluripotent Stem Cells
iPSCs
Biology
Mitochondrion
Regenerative medicine
law.invention
03 medical and health sciences
0302 clinical medicine
Confocal microscopy
law
Humans
cell-cell contacts
Induced pluripotent stem cell
Cells, Cultured
Cellular Senescence
iPSC
Autophagy
aging
Cell Biology
Middle Aged
Microvesicles
Cell biology
mitochondria
030104 developmental biology
FIB/SEM
030220 oncology & carcinogenesis
Intracellular
cell-cell contact
Research Paper
Subjects
Details
- Language :
- English
- ISSN :
- 19454589
- Volume :
- 9
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Aging (Albany NY)
- Accession number :
- edsair.doi.dedup.....a2dced5ca8aafa9375520614cde2879b