PMID- 25437179 OWN - NLM STAT- MEDLINE DCOM- 20151130 LR - 20181202 IS - 1557-8534 (Electronic) IS - 1547-3287 (Print) IS - 1547-3287 (Linking) VI - 24 IP - 5 DP - 2015 Mar 1 TI - Umbilical cord mesenchymal stromal cells affected by gestational diabetes mellitus display premature aging and mitochondrial dysfunction. PG - 575-86 LID - 10.1089/scd.2014.0349 [doi] AB - Human umbilical cord mesenchymal stromal cells (hUC-MSCs) of Wharton's jelly origin undergo adipogenic, osteogenic, and chondrogenic differentiation in vitro. Recent studies have consistently shown their therapeutic potential in various human disease models. However, the biological effects of major pregnancy complications on the cellular properties of hUC-MSCs remain to be studied. In this study, we compared the basic properties of hUC-MSCs obtained from gestational diabetes mellitus (GDM) patients (GDM-UC-MSCs) and normal pregnant women (N-UC-MSCs). Assessments of cumulative cell growth, MSC marker expression, cellular senescence, and mitochondrial function-related gene expression were performed using a cell count assay, senescence-associated beta-galactosidase staining, quantitative real-time reverse transcription-polymerase chain reaction, immunoblotting, and cell-based mitochondrial functional assay system. When compared with N-UC-MSCs, GDM-UC-MSCs showed decreased cell growth and earlier cellular senescence with accumulation of p16 and p53, even though they expressed similar levels of CD105, CD90, and CD73 MSC marker proteins. GDM-UC-MSCs also displayed significantly lower osteogenic and adipogenic differentiation potentials than N-UC-MSCs. Furthermore, GDM-UC-MSCs exhibited a low mitochondrial activity and significantly reduced expression of the mitochondrial function regulatory genes ND2, ND9, COX1, PGC-1alpha, and TFAM. Here, we report intriguing and novel evidence that maternal metabolic derangement during gestation affects the biological properties of fetal cells, which may be a component of fetal programming. Our findings also underscore the importance of the critical assessment of the biological impact of maternal-fetal conditions in biological studies and clinical applications of hUC-MSCs. FAU - Kim, Jooyeon AU - Kim J AD - 1 Departments of Pathology, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea. FAU - Piao, Ying AU - Piao Y FAU - Pak, Youngmi Kim AU - Pak YK FAU - Chung, Dalhee AU - Chung D FAU - Han, Yu Mi AU - Han YM FAU - Hong, Joon Seok AU - Hong JS FAU - Jun, Eun Jeong AU - Jun EJ FAU - Shim, Jae-Yoon AU - Shim JY FAU - Choi, Jene AU - Choi J FAU - Kim, Chong Jai AU - Kim CJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150114 PL - United States TA - Stem Cells Dev JT - Stem cells and development JID - 101197107 SB - IM EIN - Stem Cells Dev. 2015 May 15;24(10):1263. PMID: 25928834 MH - Cell Differentiation MH - Cell Proliferation MH - Cells, Cultured MH - Cellular Senescence MH - Diabetes, Gestational/metabolism/*pathology MH - Female MH - Gene Expression MH - Humans MH - Mesenchymal Stem Cells/*physiology MH - Mitochondria/*metabolism MH - Oxidative Phosphorylation MH - Pregnancy MH - Umbilical Cord/pathology PMC - PMC4333320 EDAT- 2014/12/02 06:00 MHDA- 2015/12/15 06:00 PMCR- 2016/03/01 CRDT- 2014/12/02 06:00 PHST- 2014/12/02 06:00 [entrez] PHST- 2014/12/02 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] PHST- 2016/03/01 00:00 [pmc-release] AID - 10.1089/scd.2014.0349 [pii] AID - 10.1089/scd.2014.0349 [doi] PST - ppublish SO - Stem Cells Dev. 2015 Mar 1;24(5):575-86. doi: 10.1089/scd.2014.0349. Epub 2015 Jan 14.