Enhanced chondrogenic differentiation of iPS cell-derived mesenchymal stem/stromal cells via neural crest cell induction for hyaline cartilage repair
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PROVIDER: PRJNA958215 | ENA |
REPOSITORIES: ENA
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Project description:Generate high-quality cartilage spheroids in vitro from iMSCs for regenerative medicine and tissue engineering
2023-04-30 | GSE230303 | GEO
Project description:Here, we developed a simple xeno- and feeder-free protocol for human hyaline cartilage production in vitro using hydrogel-cultured multi-tissue organoids (MTO). We investigate gene regulatory networks during spontaneous hiPSC-MTO differentiation using RNA sequencing and bioinformatic analyses. We find the interplays between BMPs and neural FGF pathways are associated with MTO phenotype transition. We recognize TGF-beta/BMP and Wnt signaling likely contribute to the long-term maintenance of cartilage growth and specific increase in articular cartilage development. By comparing MTO cartilage transcription signature with human lower limb chondrocytes, we observe MTO chondrocytes show strong correlation with fetal lower limb cartilage tissues. Collectively, our findings describe self-organized emergence of MTO hyaline cartilage, its associated molecular pathways, and spontaneous adoption of articular cartilage development trajectories by MTO.
2022-09-12 | GSE184007 | GEO
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: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. Experiment Overall Design: Characterization chondrogenic progenitor cells in P1 of 3 male and 3 female patients with late-stage OA in comparison to healthy chondrocytes in P1
2008-04-07 | E-GEOD-10575 | biostudies-arrayexpress
Project description:We used human fetal bone marrow-derived mesenchymal stromal cells (hfMSCs) differentiating towards chondrocytes as an alternative model for the human growth plate (GP). Our aims were to study gene expression patterns associated with chondrogenic differentiation to assess whether chondrocytes derived from hfMSCs are a suitable model for studying the development and maturation of the GP. hfMSCs efficiently formed hyaline cartilage in a pellet culture in the presence of TGFB3 and BMP6. Microarray and principal component analysis were applied to study gene expression profiles during chondrogenic differentiation. A set of 232 genes was found to correlate with in vitro cartilage formation. Several identified genes are known to be involved in cartilage formation and validate the robustness of the differentiating hfMSC model. KEGG pathway analysis using the 232 genes revealed 9 significant signaling pathways correlated with cartilage formation. To determine the progression of growth plate cartilage formation, we compared the gene expression profile of differentiating hfMSCs with previously established expression profiles of epiphyseal GP cartilage. As differentiation towards chondrocytes proceeds, hfMSCs gradually obtain a gene expression profile resembling epiphyseal GP cartilage. We visualized the differences in gene expression profiles as protein interaction clusters and identified many protein clusters that are activated during the early chondrogenic differentiation of hfMSCs showing the potential of this system to study GP development. To determine the progression of growth plate cartilage formation, we compared the gene expression profile of differentiating hfMSCs with previously established expression profiles of epiphyseal GP cartilage. As differentiation towards chondrocytes proceeds, hfMSCs gradually obtain a gene expression profile resembling epiphyseal GP cartilage. We visualized the differences in gene expression profiles as protein interaction clusters and identified many protein clusters that are activated during the early chondrogenic differentiation of hfMSCs showing the potential of this system to study GP development. RNA fhMSCs of chondrogenically differentiating fhMSCs was isolated at week, 0, 1, 2, 3, 4 and 5. Moreover, RNA of 4 human growth plates from was isolated.
2013-04-22 | E-GEOD-40942 | biostudies-arrayexpress
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:Hyaloid cartilage fibrosis is one of the important reasons for the poor prognosis of advanced osteoarthritis (OA), and is the main factor leading to joint stiffness and deformity. However, the mechanism of hyaline cartilage fibrosis remains largely unclear. Here we report that DDX5, one of the founding members of the DEAD-box RNA helicase family, was dramatically down-regulated in the degenerated articular cartilage of aged mice, and patients with OA, mouse destabilization of the medial meniscus (DMM) models，and cytokine (Interleukin (IL)-1β and tumor necrosis factor (TNF)-α) stimulation.In vitro and in vivo experimental findings that inhibition of DDX5 expression increases the fibrocartilage phenotype by reduction collagen type I (COL I) protein expression and up-regulate collagen type II (COL II) protein expression. In addition, The reduction of DDX5 aggravate cartilage degradation by induce the production of cartilage degrading enzymes. In addition, DDX5 induced exon 25 skip of FN1-AS and exon 14 skip of PLOD2-AS produced a transcript (termed FN1-AS1-SE25 and PLOD2-AS-SE14). The reduction in DDX5 results in an increase in the FN1-AS-WT and PLOD2-AS-WT variants.
2024-02-05 | GSE226983 | GEO
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:Chondrocytes from extra fingers exhibited a high proliferative capacity: the cells reached to population doublings (PD) 30-35 within 4 weeks before replicative senescence. The propagated cells formed hyaline cartilage at 2 weeks after subcutaneous implantation of NOD/Scid/IL-2 receptor gamma knock out (NOG) mice, and the generated cartilage showed enchondral ossification at 8 to 12 weeks. The cartilage formation with osteogenesis depends on the number of cell division in vitro. Keywords: NCCH BioResource Affymetrix human U133 plus 2.0 array was used to transcriptionally profile to determine the expression changes in epiphyseal cartilage.
2011-03-22 | E-GEOD-17368 | biostudies-arrayexpress
Project description:We have used a disc-shaped self-gelling alginate hydrogel as a scaffold for in vitro chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells. The comparison of monolayer cells and alginate embedded cells with or without differentiation medium allowed us to perform a detailed kinetic study of the expression of a range of genes and proteins known to be involved in chondrogenesis, using real-time polymerase chain reaction, fluorescence immunohistochemistry, and glycosaminoglycan measurement in the supernatant. mRNA encoding type II collagen (COL2), COL10, aggrecan, and SOX5, 6, and 9 were greatly elevated already at day 7, whereas COL1 and versican mRNA were gradually reduced. COL2 and aggrecan were dispersed throughout the extracellular matrix at day 21, whereas COL10 distribution was mainly intra/pericellular. COL1 seemed to be produced by only some of the cells. SOX proteins were predominantly localized in the nuclei. Then, using microarray analysis, we identified a signature cluster of extracellular matrix and transcription factor genes upregulated during chondrogenesis similar to COL2A1, and clusters of genes involved in immune responses, blood vessel development, and cell adhesion downregulated similar to the chemokine CXCL12. Analysis of the signature chondrogenic clusters, including novel potential marker genes identified here, may provide a better understanding of how the stem cell fate could be directed to produce perfect hyaline cartilage implants Comparison of gene expression patterns in 4 BM-MSC donors, before and after chondrogenic differentiation in alginate (BM-MSCs and DIF)
2012-08-17 | E-GEOD-40175 | biostudies-arrayexpress