Cellular Aging of Mesenchymal Stem Cells (miRNA)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE9664 | GEO | 2008/07/29
SECONDARY ACCESSION(S): PRJNA103541
REPOSITORIES: GEO
Similar Datasets
Project description:To determine gene expression changes during in vitro senescence of MSC we have analyzed differential expression of the corresponding early passage (P2) and senescent passage (PX). There were global changes in the gene expression profile that were reproducible in three independent donor samples. Experiment Overall Design: Mesenchymal Stem Cells (MSC) were isolated from human bone marrow (BM) as described before (Wagner et al., 2005, Exp Hematol, 33, 1402-1416; Wagner et al., Exp Hematol, 34, 536-548). Cells were always replated when grown to confluency. A sample for RNA isolation was taken at every passage until the cells finally became senescent: they became much larger with irregular and flat shape. The nucleus became more circumscribed in phase contrast microscopy. The cytoplasm began to be granular with many inclusions and there was more cell debris. Global gene expression profiles were analyzed to determine molecular changes between corresponding early passage (P2) and senescent passage (PX) in three donor samples. In addition we have analyzed different passages of donor 1 (P2, P3, P4, P5, P6, P7, P8, P10, and P11) to determine changes in the course of cellular aging. Data were median normalized and compared to P2 of the corresponding donor sample.
2008-10-20 | E-GEOD-9593 | biostudies-arrayexpress
Project description:To determine gene expression changes during in vitro senescence of MSC we have analyzed differential expression of the corresponding early passage (P2) and senescent passage (PX). There were global changes in the gene expression profile that were reproducible in three independent donor samples. Keywords: Replicative senescence, time course
2008-07-29 | GSE9593 | GEO
Project description:In this study, we have analyzed DNA methylation changes upon long-term culture and aging of MSC by using the HumanMethylation27 BeadChip assessing 27,578 unique CpG sites. Cells were taken from bone marrow aspirates from iliac crest (BM) of healthy donors or from the caput femoris (HIP) of elderly patients that received femoral head prosthesis.Overall, the methylation pattern was maintained throughout both long-term culture and aging but highly significant differences were observed at specific CpG sites. Notably, methylation changes in MSC were related in long-term culture and aging in vivo. Mesenchymal stromal cells (MSC) were isolated from human bone marrow as described before (Wagner et al., 2006, Exp Hematol, 34, 536-548; Wagner et al.,2008, PLoS One 21;3(5):e2213.; Wagner et al., PLoS One. 2009 Jun 9;4(6):e5846.) Cells were always replated when grown to confluency. A sample for DNA isolation was taken at every passage until the cells finally became senescent. For methylation profiles upon long-term culture we used the samples of early passage (P2) and senescent passage (PX). For methylation profiles upon aging we have only used the samples of passage 2 of younger and elderly donors. Gene expression data of these samples have been previously deposited unter GSE9593 and GSE12274.
2010-05-14 | E-GEOD-17448 | biostudies-arrayexpress
Project description:The bone marrow microenvironment in Large Granular Lymphocyte Leukemia (LGLL) patients has been unexplored for it’s role in the development of cytopenias, which lead to complications resulting in the most prominent causes of morbidity and mortality. We used microarrays on primary mesenchymal stem cell (MSC) cultures isolated from bone marrow aspirates from LGLL patients to identify genetic programs that may lead to the observed profibrotic and extrinsically senescent phenotype. Isolated primary MSC cultures were maintained under reduced oxygen conditions (2%). All cultures displayed trilineage pluripotency (adipogenesis, osteogenesis, and chondrogenesis). For comparison, normal MSC cultures in early passage (p2-3; same number of population doublings as the LGLL MSCs) and later passage (p7-9; same time spent in culture as the LGLL MSCs) are included.
2013-04-20 | E-GEOD-37470 | biostudies-arrayexpress
Project description:<p><strong>BACKGROUND:</strong> Periodontal ligament mesenchymal stem cells (PDLSCs) are a promising cell resource for cell-based regenerative medicine in dentistry. PDLSCs inevitably acquire a senescent phenotype after prolonged in vitro expansion, and the key regulators of cells during replicative senescence remain unclear.</p><p><strong>METHODS:</strong> We cultured periodontal ligament stem cells to passages 4, 10 and 20 (P4, P10, P20). The senescent phenotypes, proliferation and migration ability of PDLSCs (P4, P10, P20) were detected, and non-targeted metabonomic sequencing was performed. We treated PDLSCs with AICAR and detected the expression of FOXO1, FOXO3a, FOXO6 and AMPK phosphorylation (p-AMPK) levels of replicating senescent PDLSCs to explore the correlation between the metabolic changes and the AMPK pathway.</p><p><strong>RESULTS:</strong> Immunofluorescence staining of γ-H2AX, β-galactosidase staining, cell scratch test and qPCR were performed to confirm the occurrence of replicative senescence in PDLSCs during passaging. Three groups of cells at passage 4 (P4), passage 10 (P10) and passage 20 (P20) were collected for non-targeted metabolomics analysis. Metabonomic sequencing showed that the metabolism of replicative senescence in PDLSCs varied significantly. In particular, the content of fatty acid metabolites decreased with senescence, including capric acid, stearic acid, myristic acid and dodecanoic acid. KEGG pathway analysis showed that the AMPK signaling pathway was closely related to AMP levels. The AMP:ATP ratio increased in senescent PDLSCs; however, the levels of p-AMPK and the profile of FOXO1 and FOXO3a, which are downstream of the AMPK signaling pathway, decreased with senescence. We treated PDLSCs with AICAR, an activator of the AMPK pathway, and the phosphorylated AMPK level at P20 PDLSCs was partially restored. </p><p><strong>CONCLUSION:</strong> In summary, our study suggests that the metabolic process of PDLSCs is active in the early stage of senescence, prefers to consume fatty acids, and is attenuated in the later stages of senescence. AMP accumulates in replicative senescent PDLSCs; however, the sensitivity of AMPK phosphorylation sites is impaired, causing senescent PDLSCs to fail to respond to changes in energy metabolism. Our findings provide a new basis for the clinical application of periodontal ligament stem cells.</p>
2022-11-15 | MTBLS4568 | MetaboLights
Project description:In the present study we analyzed the effect of cellular senescence on the transcriptome of human mesenchymal stem cells (hMSC; alternatively named mesenchymal stromal cells) from bone marrow. Human MSC were isolated from femoral heads of non-osteoporotic donors after total hip arthroplasty. Cells were isolated from human bone marrow according to the previously described protocol (Noth et al., 2002, J Orthop Res, 20/5, 1060-1069) under agreement of the local Ethics Committee of the University of Würzburg. Bone marrow was obtained of femoral heads after total hip arthroplasty due to osteoarthritis and/or hip dysplasia. MSC were replated after reaching 70-90% confluence until they entered state of cellular senescence. RNA samples of control cells were taken from passage 1 or passage 2.
2012-02-22 | E-GEOD-35957 | biostudies-arrayexpress
Project description:Cells in culture undergo replicative senescence and unequivocally stop proliferation after a limited number of cell divisions. In this study, we have expanded mesenchymal stem cells (MSC) from human adipose tissue and analyzed genetic and epigenetic sequels. The subpopulation of highly proliferative cells and the in vitro differentiation potential decayed already within early passages. Relevant chromosomal aberrations were not detected by karyotyping and SNP-microarrays. Comparison of early and late passage of five samples of mesenchymal stem cells from human adipose tissue.
2013-02-15 | E-GEOD-27135 | biostudies-arrayexpress
Project description:In the present study we analyzed the effect of advanced donor age on the transcriptome of human mesenchymal stem cells (hMSC; alternatively named mesenchymal stromal cells) from bone marrow. Human MSC of elderly and middle-aged patients without symptoms of osteoporosis were isolated from femoral heads after total hip arthroplasty. Cells were isolated from human bone marrow according to the previously described protocol (Noth et al., 2002, J Orthop Res, 20/5, 1060-1069) under agreement of the local Ethics Committee of the University of Würzburg. Bone marrow was obtained of femoral heads after total hip arthroplasty due to osteoarthritis and/or hip dysplasia. RNA samples were taken from passage 1 or passage 2.
2012-02-22 | E-GEOD-35955 | biostudies-arrayexpress
Project description:Human mesenchymal stem cells (hMSCs) promote endogenous tissue regeneration and have become a promising candidate for cell therapy. However, in vitro culture expansion of hMSCs induces a rapid decline of stem cell properties through replicative senescence. Here we characterize metabolic profiles of hMSCs during expansion. We show that alterations of cellular nicotinamide adenine dinucleotide (NAD+ /NADH) redox balance and activity of the Sirtuin (Sirt) family enzymes regulate cellular senescence of hMSCs. Treatment with NAD+ precursor nicotinamide increases the intracellular NAD+ level and re-balances the NAD+ /NADH ratio, with enhanced Sirt-1 activity in hMSCs at high passage, partially restores mitochondrial fitness and rejuvenates senescent hMSCs. By contrast, human fibroblasts exhibit limited senescence as their cellular NAD+ /NADH balance is comparatively stable during expansion. These results indicate a potential metabolic and redox connection to replicative senescence in adult stem cells and identify NAD+ as a metabolic regulator that distinguishes stem cells from mature cells. This study also suggests potential strategies to maintain cellular homeostasis of hMSCs in clinical applications.
2021-09-09 | PXD022395 | Pride
Project description:Cellular senescence is characterised by a state of permanent cell cycle arrest. While cellular senescence is a recognised driver of organismal ageing, the extent of heterogeneity within and between different senescent cell populations remains largely unclear. Here we combined cell biological and single cell RNA-sequencing approaches to investigate heterogeneity of replicative senescence in human ESC-derived mesenchymal stem cells (esMSCs) as MSCs are the cell type of choice for the majority of current stem cell herapies and senescence of MSC is a recognized driver of organismal ageing. We identified three senescing esMSC subpopulations and their associated maker genes, allowing us to identify potential drug targets that may delay the emergence of senescent MSCs in vitro and perhaps in vivo in the future.
2023-04-30 | GSE200157 | GEO