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

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.

SUBMITTER: Colasuonno F

PROVIDER: S-EPMC5680563 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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

Colasuonno Fiorella F Borghi Rossella R Niceforo Alessia A Muzzi Maurizio M Bertini Enrico E Di Giulio Andrea A Moreno Sandra S Compagnucci Claudia C

Aging 20171001 10

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 ...[more]

PMID: 29064821

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Project description:BACKGROUND:The discovery of induced pluripotent stem cells (iPSCs) opened the possibilities for reprogramming cells back to a pluripotent state. Because of no apparent ethical issues connected with donation and derivation of biomaterial, iPSCs are considered as a research alternative to ethically highly disputed human embryonic stem cells (hESCs). However, the unique character of iPSCs leads to numerous ethical considerations, which mainly concern the issue of donor information and consent for the use of biospecimen in research and drug evaluation. METHODS:For the purpose of this analysis, we conducted a review of the literature in the PubMed/MEDLINE and Web of Science databases. The search algorithm led to the identification of 1461 results. After removing duplicates and screening of title and abstract, 90 articles were found to be relevant to the study's objective. Full texts of these articles were apprised and 62 articles were excluded at this step for not properly addressing the study's objective. In the final step, 28 articles were included in the analysis. Analyzed were both research and non-research manuscripts published in peer-reviewed journals. RESULTS:In the case of iPSC research, the information process should be guided by general frameworks established for research on human subjects but also by specific characteristics of iPSCs. We determined four main domains and 12 thematic subdomains that should be included in donor information. Our results show that majority of authors agree to the content of information with regard to the areas of general information, storage of cells, and protection of privacy. Two main issues that are discussed in the literature are donor's consent for use in future studies and the process of donor information. CONCLUSIONS:Given the unique character of iPSCs and the possibility of their various uses in the future, the content of donor information should contain specific information central to iPSC research. Effective methods of communicating information to donors should combine written and oral information with the possible use of multimedia.

Dataset Information

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

Publications

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

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