title: Epigenetic rejuvenation of mesenchymal stromal cells derived from induced pluripotent stem cells.
abstract: 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.
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical School, 52074 Aachen, Germany.
authors.forename: Joana
authors.initials: J
authors.lastname: Frobel
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical School, 52074 Aachen, Germany.
authors.forename: Hatim
authors.initials: H
authors.lastname: Hemeda
authors.affiliation: Aachen Institute for Advanced Study in Computational Engineering Science (AICES), RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lenz
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical School, 52074 Aachen, Germany.
authors.forename: Giulio
authors.initials: G
authors.lastname: Abagnale
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical School, 52074 Aachen, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Joussen
authors.affiliation: Interdisciplinary Center for Clinical Research (IZKF), RWTH Aachen University Medical School, 52074 Aachen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Denecke
authors.affiliation: Center for Physiology and Pathophysiology, Institute for Neurophysiology, University of Cologne, 50931 Cologne, Germany.
authors.forename: Tomo
authors.initials: T
authors.lastname: Sarić
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical School, 52074 Aachen, Germany; Institute for Biomedical Engineering, Cell Biology, RWTH Aachen University Medical School, 52074 Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zenke
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical School, 52074 Aachen, Germany. Electronic address: wwagner@ukaachen.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wagner
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D059467:Transcriptome