Journal
STEM CELL REPORTS
Volume 3, Issue 3, Pages 414-422Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2014.07.003
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Funding
- StemCellFactory consortium
- European Union (European Regional Development Fund - Investing in your future) and German Federal State of North Rhine-Westphalia
- Stem Cell Network NRW
- German Research Foundation [WA 1706/3-2, WA 1706/2-1, ZE 432/5-2, ZE 432/6-1]
- Else-Kroner Fresenius Stiftung
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Standardization of mesenchymal stromal cells (MSCs) remains a major obstacle in regenerative medicine. Starting material and culture expansion affect cell preparations and render comparison between studies difficult. In contrast, induced pluripotent stem cells (iPSCs) assimilate toward a ground state and may therefore give rise to more standardized cell preparations. We reprogrammed MSCs into iPSCs, which were subsequently redifferentiated toward MSCs. These iPS-MSCs revealed similar morphology, immunophenotype, in vitro differentiation potential, and gene expression profiles as primary MSCs. However, iPS-MSCs were impaired in suppressing T cell proliferation. DNA methylation (DNAm) profiles of iPSCs maintained donor-specific characteristics, whereas tissue-specific, senescence-associated, and age-related DNAm patterns were erased during reprogramming. iPS-MSCs reacquired senescence-associated DNAm during culture expansion, but they remained rejuvenated with regard to age-related DNAm. Overall, iPS-MSCs are similar to MSCs, but they reveal incomplete reacquisition of immunomodulatory function and MSC-specific DNAm patterns-particularly of DNAm patterns associated with tissue type and aging.
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