Epigenetic rejuvenation of mesenchymal stromal cells derived from induced pluripotent stem cells

Joana Frobel, Hatim Hemeda, Michael Lenz, Giulio Abagnale, Sylvia Joussen, Bernd Denecke, Tomo Sarić, Martin Zenke, Wolfgang Wagner

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)414-22
Number of pages9
JournalStem Cell Reports
Issue number3
Publication statusPublished - 9 Sep 2014


  • Cell Differentiation
  • Cells, Cultured
  • DNA Methylation
  • Epigenesis, Genetic
  • Humans
  • Induced Pluripotent Stem Cells
  • Mesenchymal Stromal Cells
  • Transcriptome

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