Gene array comparison of highly and poorly chondrogenic clones of adult human mesenchymal stem cells (MSCs)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE54684 | GEO | 2015/04/30
SECONDARY ACCESSION(S): PRJNA237358
REPOSITORIES: GEO
Similar Datasets
Project description:MSCs are a heterogeneous population of cells with different capacities for lineage differentiation. MSC clones were prepared from a single adult human bone marrow sample and screened for their chondrogenic capacity using cartilage tissue engineering (measured by type II collagen content). The aim was to compare genes expressed by highly and poorly chondrogenic clones to identify genes associated with those MSCs with an enhanced capacity for cartilage formation. The 4 most highly chondrogenic and the 4 least chondrogenic MSC clones identified following screening by cartilage tissue engineering were selected for gene array comparison using Affymetrix microarrays.
2015-04-30 | E-GEOD-54684 | biostudies-arrayexpress
Project description:Human bone marrow derived mesenchymal stromal cells (BMSCs) represent a putative cell source candidate for tissue engineering based strategies to repair cartilage and bone. However, traditional isolation of BMSCs by their preference to adhere to plastic leads to very heterogeneous cell populations and may account for high inter-donor variability and unpredictability of chondrogenic differentiation out-come. Identification of a cell fraction with higher chondrogenic capacity and reduced variance in basic chondrogenic differentiation could further aid the process for developing BMSC-based cartilage and bone regeneration approaches. Since single cell derived clones isolated from fresh bone marrow aspirates show a broad range of chondrogenic capacity, we assessed whether the gene expression profile of clones with high and low chondrogenic capacity differs. While a clustering between high and low chondrogenic capacity clones was observed for one donor, donor-to-donor variability drastically hampered the possibility to achieve conclusive results when different donors were considered. NCAM1/CD56 as identified by the transcriptomic analysis of one donor was still up-regulated in clones with higher chondrogenic capacity and we showed that enriching expanded multiclonal BMSCs for CD56+ expression led to an increase in chondrogenic capacity, though still highly affected by donor-to-donor variability. Our study finally suggests that the definition of predictive marker(s) for BMSCs chondrogenesis is challenged by the high donor’s heterogeneity of these cells. Moreover, we hypothesis that multiple pathways may be involved in determining the chondrogenic potential of BMSCs, making the identification of putative markers still an open issue.
2020-01-13 | GSE111822 | GEO
Project description:Bovine chondrocyte-seeded and mesenchymal stem cell (MSC)-seeded agarose were cultured for 28 days in chemically defined media containing 10 ng/mL TGF-beta3. Chondrogenic differentiated MSCs were compared to chondrocytes at this timepoint and to undifferentiated MSCs harvested at day 0. Donor-matched sets of chondrocytes and MSCs were used, with three donors total.
2010-10-02 | E-GEOD-18394 | biostudies-arrayexpress
Project description:Bovine chondrocyte-seeded and mesenchymal stem cell (MSC)-seeded agarose were cultured for 28 days in chemically defined media containing 10 ng/mL TGF-beta3. Chondrogenic differentiated MSCs were compared to chondrocytes at this timepoint and to undifferentiated MSCs harvested at day 0.
2010-10-02 | GSE18394 | GEO
Project description:Fibroblast growth factor-2 delays the loss of chondrogenic potential in adult bone marrow-derived mesenchymal stem cells We compared human mesenchymal stem cells (hMSCs), expanded long-term with and without fibroblast growth factor (FGF) supplementation, with respect to their proliferation rate, and ability to differentiate along the chondrogenic pathway in vitro. hMSCs expanded in FGF-supplemented medium proliferated more rapidly than those expanded under control conditions. Aggregates of FGF-treated cells exhibited chondrogenic differentiation at passages 1 through 7, although, in some of the preparations, chondrogenic differentiation was somewhat diminished after seventh passage. Aggregates made with control cells differentiated along the chondrogenic lineage at first passage but exhibited only marginal chondrogenic differentiation after four passages and failed to form cartilage after seven passages. Microarray analysis of gene expression identified 334 transcripts that were differentially expressed in fourth passage control cells which had reduced chondrogenic potential compared to fourth passage FGF-treated cells which retained this differentiation capacity and 243 transcripts that were differentially expressed when comparing them to first passage control cells which were also capable of differentiating into chondrocytes. The intersection of these analyses yielded 49 transcripts that were differentially expressed in cells that exhibited chondrogenic differentiation in vitro compared to cells that did not. These preliminary data must now be validated to verify whether the different gene expression profiles translate into functional differences. These findings suggest that care should be exercised when extensively expanding these cells for cartilage tissue engineering applications. Keywords: time course and treatment
2009-10-29 | GSE14828 | GEO
Project description:In osteoarthritis (OA), impairment of cartilage regeneration can be related to a defective chondrogenic differentiation of mesenchymal stromal cells (MSCs). Therefore, understanding the proteomic- and metabolomic-associated molecular events during the chondrogenesis of MSCs could provide alternative targets for therapeutic intervention. Here, a SILAC-based proteomic analysis identified 43 proteins related with metabolic pathways whose abundance was significantly altered during the chondrogenesis of OA human bone marrow MSCs (hBMSCs). Then, the level and distribution of metabolites was analyzed in these cells and healthy controls by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), leading to the recognition of characteristic metabolomic profiles at the early stages of differentiation. Finally, integrative pathway analysis showed that UDP-glucuronic acid synthesis and amino sugar metabolism were downregulated in OA hBMSCs during chondrogenesis compared to healthy cells. Alterations in these metabolic pathways may disturb the production of hyaluronic acid (HA) and other relevant cartilage extracellular matrix (ECM) components. This work provides a novel integrative insight into the molecular alterations of osteoarthritic MSCs and potential therapeutic targets for OA drug development through the enhancement of chondrogenesis.
2020-01-27 | PXD012879 | Pride
Project description:Osteoarthritis (OA) is the most prevalent chronic joint disease that affects a majority of the elderly. Chondrogenic progenitor cells (CPCs) reside in late stage OA cartilage tissue, producing a fibrocartilagenous extra-cellular matrix and can be manipulated in-vitro, to deposit proteins of healthy articular cartilage. CPCs are under control of SOX9 and RUNX2 and in order to enhance their chondrogenic potential, we found that RUNX2 plays a pivotal role in chondrogenesis. In another approach, CPCs carrying a knockout of RAB5C, a protein involved in endosomal trafficking, demonstrated elevated expression of various chondrogenic markers including the SOX trio and displayed an increased COL2 deposition, whereas no changes of COL1 deposition was observed. We report RAB5C as an attractive target for future therapeutic approaches to increase the COL2 content in the diseased joint.
2021-09-09 | PXD021785 | Pride
Project description:Osteoarthritis (OA) is a degenerative joint disease that involves destruction of articular cartilage and eventually leads to disability. Mesenchymal stem cells (MSCs) reside in healthy and diseased cartilage, and through their chondrogenic potential may provide a strategy for cartilage repair. To this end, we performed an image-based, high throughput screen and identified the small molecule, kartogenin, that promotes selective MSC differentiation into chondrocytes (EC50=100nM), shows chondroprotective effects in vitro, and is efficacious in two OA animal models. Kartogenin binds filamin A and induces chondrogenesis by regulating the CBFbeta-RUNX1 transcriptional program. This work provides new insights into the control of chondrogenesis that may ultimately lead to an effective stem-cell based therapy for osteoarthritis. one compound, three doses, two time points, a vehicle control
2012-05-01 | E-GEOD-35546 | biostudies-arrayexpress
Project description:The regeneration of diseased hyaline cartilage remains a great challenge, mainly because degeneration activities after major injury or due to age-related processes overwhelm the self-renewal capacity of the tissue. We show that repair tissue from human articular cartilage of late stages of osteoarthritis harbor a unique progenitor cell population, termed chondrogenic progenitor cells exhibiting stem cell characteristics, such as multipotency, lack of immune system activation and, in particular, migratory activity. The isolated CPC exhibit a high chondrogenic potential and were able to populate diseased tissue in vivo. Moreover, down-regulation of the osteogenic transcription factor runx-2 enhanced the expression of the chondrogenic transcription factor sox-9 and consequently the matrix synthesis potential of chondrogenic progenitor cells. Our results, while offering new insight into the biology of progenitor cells from diseased cartilage tissue, might assist future strategies to treat late stages of osteoarthritis. Keywords: cell type comparison
2008-02-21 | GSE10575 | GEO
Project description:Mutations in the RMRP gene are the origin of cartilage-hair hypoplasia. Cartilage-hair hypoplasia is associated with severe dwarfism caused by impaired skeletal development. However, it is not clear why mutations in the RMRP gene lead to skeletal dysplasia. Viperin is a known substrate of RMRP. Since chondrogenic differentiation of the growth plate is required for development of the long bones, we hypothesized that viperin functions as a chondrogenic regulator downstream of RMRP. Viperin protein is expressed throughout the stages of chondrogenic differentiation in vivo. Viperin gene expression is increased during knockdown of Rmrp RNA in the ATDC5 model for chondrogenic differentiation. Viperin is expressed during ATDC5 chondrogenic differentiation. Viperin knockdown reduces, while viperin overexpression increases overall protein secretion, with CXCL10 identified as a potential target via mass spectrometry-proteomics. CXCL10 protein expression is reduced during knockdown and increased during overexpression of viperin and CXCL10 protein expression coincides with viperin expression in ATDC5 chondrogenic differentiation. Viperin knockdown induces, while viperin overexpression reduces TGFβ activity. Furthermore, viperin knockdown conditioned media increases, while viperin overexpression conditioned media reduces chondrogenic differentiation of ATDC5 cells. TGFβ target genes Pai1 and Smad7 are increased during knockdown and reduced during overexpression of viperin. Moreover, TGFβ activity is reduced when differentiating ATDC5 cells are exposed to CXCL10 and, acting as a viperin overexpression mimic, CXCL10 similarly reduces chondrogenic differentiation of ATDC5. Lastly, we show that in CHH patient cells, RMRP expression is reduced and viperin expression is increased, coinciding with reduced chondrogenic differentiation and increased CXCL10 expression, possibly explaining the CHH phenotype. Together our data show that viperin may play a pivotal role in chondrogenic differentiation, with potential consequences for cartilage-hair hypoplasia pathobiology.
2019-02-15 | PXD006999 | Pride