Epigenetic rejuvenation of mesenchymal stromal cells derived from induced pluripotent stem cells.
Stem Cell Reports
; 3(3): 414-22, 2014 Sep 09.
Article
in En
| MEDLINE
| ID: mdl-25241740
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Epigenesis, Genetic
/
Induced Pluripotent Stem Cells
/
Mesenchymal Stem Cells
Limits:
Humans
Language:
En
Journal:
Stem Cell Reports
Year:
2014
Document type:
Article
Affiliation country:
Germany