Expression data from human fetal cardiac MSCs
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Karl-Henrik Grinnemo
PROVIDER: E-GEOD-78047 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The instrinsic regenerative capacity of human fetal cardiac mesenchymal stromal cells (MSCs) has not been fully characterised. Here we demonstrate that we can expand cells with characteristics of cardiovascular progenitor cells from the MSC population of human fetal hearts with only minor fluctuations over time in culture (from day 15 to day 48). We used microarray to compare the gene-expression profile of cultured human fetal cardiac MSCs over time (from day 15 to day 48).
2016-02-19 | GSE78047 | GEO
Project description:Rationale and Objectives: Cellular therapies are hampered by poor survival and growth of grafts. We recently showed that the survival and repairing capacity of transplanted adult cells may be improved by co-expression of the anti-senescence telomerase reverse transcriptase (TERT) and anti-apoptotic myocardin (MYOCD). The current study aimed at testing whether forced co-expression of TERT and MYOCD improves post-infarct revascularization and tissue repair by adipose tissue-derived mesenchymal stromal cells (AT-MSCs). Methods: We transplanted AT-MSCs engineered to overexpress MYOCD and TERT in a murine model of acute myocardial infarction (AMI). We analyzed the immunoregulatory properties of AT-MSCs on post-AMI. We characterized in vitro and in vivo paracrine effects of AT-MSCs and their interactions with murine cardiospheres (CSps), all as parts of their reparative repertoire. Results: When transplanted into infarcted hearts of C57BL/6 mice, “rejuvenated” AT-MSCs overexpressing TERT and MYOCD (rAT-MSCs) decreased fibrosis and the intrafibrotic CD3 and B220 lymphocyte infiltration, and increased arteriolar density as well as ejection fraction compared with saline or mock-transduced AT-MSCs. These effects were accompanied by increased numbers of Ki-67+ and CD117+ cells, and the expression of cardiac actin and β-myosin heavy chain within the infarcted hearts. Both rAT-MSCs and their conditioned medium (CM) stimulated intracellular Ca2+ flux in CSps. CSp-derived cells had increased survival when preconditioned with CM or exosome-enriched fraction (Exo+) from rAT-MSCs and then exposed to simulated ischemia/reperfusion. Proteomic analysis of rAT-MSCs-Exo+ predicted the activation of vascular development and the inhibition of immune cell trafficking. Elevated concentration of miR-320a, miR-150-5p and miR-126-3p associated with regulation of apoptosis and vasculogenesis was confirmed in rAT-MSCs-Exo+. Conclusions: rAT-MSCs promote vasculogenesis and cell survival and reduce post-AMI inflammatory responses in a murine model of AMI. An integrated experimental and computational analysis revealed that Exo+ is the active component of the paracrine secretion by rAT-MSCs, with pro-angiogenic and pro-survival activities.
2020-12-02 | PXD017413 | Pride
Project description:Fetal cartilage fully regenerates following injury while in adult mammals cartilage injury leads to osteoarthritis (OA). OA is characterized by cartilage breakdown and joint inflammation and associated with significant pain and socioeconomic costs. As no clinically satisfactory treatment is available to date, disease-modifying therapies aimed to achieve cartilage regeneration are urgently required. The inherent regeneration potential of fetal individuals may hold answers to this unmet need. Therefore, to characterize the differences in fetal and adult response to cartilage injury, we carried out histology and comprehensive proteome analyses on fetal (day 80/150-day gestation) and adult cartilage samples one (fetal samples) and three (adult and fetal samples) days after surgical induction of a full-thickness cartilage lesion. In addition, proteins secreted by inflamed fetal MSCs in vitro were compared with the in vivo response to injury to evaluate their therapeutic potential. Histology of synovial samples revealed the presence of neutrophils one day post injury (p.i.) and an influx of macrophages into the subsynovial tissue on day 3 p.i. in fetal samples. In contrast, adult synovial samples showed invasion of neutrophils on day 3 p.i. Activation and migration of Iba1+- macrophages of the synovial lining was observed both in fetal and adult animals. Comparative mass spectrometry revealed 57 proteins significantly up-regulated (> 2FC, FDR<0.05), and 67 proteins significantly down-regulated (<-2 FC) upon injury in adults. Neutrophil-related proteins and acute phase proteins were the two major upregulated protein groups in adult cartilage following injury compared to fetal sheep. In contrast, several immunomodulating proteins and growth factors were significantly higher expressed in the fetus than the adult. Comparison of the in vitro MSCs with the in vivo fetal proteome revealed shared upregulation of 17 proteins, which were considered to be of potential therapeutic interest. The results of this study support our molecular understanding of successful fetal cartilage healing and new therapeutic strategies to induce regeneration in adult articular cartilage by modulating the inflammatory environment. The shared protein upregulation in fetal cartilage in vivo and in fetal MSCS during in vitro inflammation supports the possible therapeutic potential of these factors in specific and fetal MSCs in general.
2022-02-17 | PXD027486 | Pride
Project description:Transcriptional profiling of human MSCs comparing control MSCs with parathyroid hormone (PTH)-stimulated MSCs. PTH-stimulated MSCs were treated with 0.1 nM recombinant human PTH (N-terminal fragment, amino acids 1-34) for 48 hours. Human MSCs were isolated from a bone marrow sample obtained from a healthy adult volunteer. Two-condition experiment: control MSCs vs. PTH-stimulated MSCs. 1 control MSCs and 1 PTH-stimulated MSCs.
2014-02-01 | E-GEOD-43148 | biostudies-arrayexpress
Project description:Expression data from Total RNA extracted from murine spleen, liver, lungs, kidneys and hearts. Sepsis was induced in C57Bl/6J mice by cecal ligation and puncture (CLP), followed 6 hours later by an intravenous injection of Mesenchymal Stem Cell (MSC) or saline. Twenty-eight hours after CLP, plasma, bronchoalveolar lavage (BAL) fluid and tissues were collected for analyses. Total RNA was extracted using Trizol (as per manufactures' instruction) followed by clean-up procedure using Qiagen RNA easy Prep (as per manufactures instructions) In the following study we hypothesized that mesenchymal stem cells (MSCs), which have documented immunomodulatory properties, would reduce sepsis-associated inflammation and organ injury in a clinically relevant model of sepsis. To identify the molecular changes associated with decreased inflammation in CLP-injured mice treated with MSCs, we analyzed the gene expression profiles from spleens, liver, lungs, kidneys and heart collected at 28 hours from 4 animals per group: sham/saline, CLP/saline, and CLP/MSCs.
2012-12-31 | E-GEOD-40180 | biostudies-arrayexpress
Project description:In response to heart failure (HF), the heart reacts by repressing adult genes and expressing fetal genes, thereby returning to a more fetal-like gene profile. To identify genes involved in this process, we carried out transcriptional analysis on murine hearts at different stages of development and adult mice with HF. Our screen identified 5-oxoprolinase (OPLAH), a member of the -Glutamyl cycle, that functions by scavenging 5-oxoproline. OPLAH depletion occurred as a result of cardiac injury, leading to elevated 5-oxoproline and oxidative stress, whereas OPLAH overexpression improved cardiac function after ischemic injury. In HF patients we observed elevated plasma 5-oxoproline levels, which were associated with a worse clinical outcome. Understanding and modulating fetal-like genes in the failing heart may lead to potential novel diagnostic, prognostic and therapeutic options in HF.
2017-11-08 | E-MTAB-5449 | biostudies-arrayexpress
Project description:Although various sources of cMSCs show similar characteristics, they are different in osteogenic potential due to their original cellular sources. Thus, this study was designed to globally explore and analyze the in vitro differentiation potential and behavior of canine bone-marrow derived mesenchymal stem cells (cBM-MSCs) and canine dental pulp stem cells (cDPSCs) toward osteogenic lineage. Global study of an in vitro osteogenic differentiation potential of the isolated cells was performed using proteomic-based analysis through mass spectrometry with dimethyl labelling method at day 7 and 14 post-induction, comparing with undifferentiated cells. The obtained results could be used as a comprehensive data and principal knowledge of the osteogenic differentiation potential of cBM-MSCs and cDPSCs in vitro and the trend of MSC-based tissue engineering for osteogenic regenerative therapy, concentrating on cMSCs application.
2021-09-08 | PXD015512 | Pride
Project description:Long-term dynamic compression enhanced the mechanical properties of MSC-seeded constructs only when loading was initiated after 21 days of chondrogenic differentiation. This study examined the molecular differences of chondrogenic MSCs compared to undifferentiated MSCs (TGF-beta vs no TGF-beta) and the effects of dynamic loading on MSC chondrogenesis (loading vs free-swelling). Free-swelling MSC-seeded constructs were cultured for 21 days in chemically defined media. Chondrogenesis was induced with TGF-beta3. Undifferentiated controls were maintained in parallel. After 21 days of chondrogenic differentiation, a subset of constructs were subjected to 21 days of dynamic compressive loading. On days 21 and 42, construct mechanical properties and biochemical content were assessed. Microarray analysis was carried out on day 3, day 21 and day 42 constructs. 6 arrays.
2010-11-01 | E-GEOD-18879 | biostudies-arrayexpress
Project description:Background: Studies suggested that mesenchymal stem cells (MSCs) have intrinsic neurogenic potential and can be differentiated into neural stem cell/ neural progenitor cells (NPCs) under specific microenvironment. Manipulation of growth factors is one of the popular method to achieve trans-lineage differentiation of MSCs. Synergistic effect of epidermal growth factor (EGF) and fibroblast growth factor 2 (bFGF) have been widely identified as basic requirement for neural differentiation to take place. Insulin-like growth factor 1 (IGF-1) also known as somatomedin C is an important growth promoting protein during embryonic development which control numerous cellular responses and biological systems. Our recent study has found that the combination of EGF, bFGF and IGF-1 could significantly improved the growth and survivability of MSCs-derived NPCs. Therefore, to understand the genomic mechanism underlying the differentiation in vitro, we have studied the miRNAs profile of MSCs-derived NPCs under IGF-1 influenced conditioned microenvironments. Objectives: To evaluate the effects of IGF-1 in trans-lineage differentiation of MSCs, we have induced MSCs into neural lineage in 3 groups; Group A (positive control) - EGF+bFGF, Group B (Treatment) - EGF+bFGF+IGF-1, and Group C (negative control/ untreated). To unravel the role of regulatory miRNAs involved in the early differentiation, we have performed detailed miRNA profiling for MSCs-derived NPCs at three time intervals (day 1, day 3 and day 5). The data has explored crucial miRNAs involved in early differentiation of MSCs into NPCs. Stage specific MSCs-derived NPCs at Passage 1 were collected for total RNA extraction at three time-points (D1, D3 and D5) and hybridization on Affymetrix miRNA geneChip 2.0 arrays. Each experiment were repeated three times independently (Exp 1, Exp 2 and Exp 3). Group A served as positive control (EGF+bFGF), Group B as treatment (EGF+bFGF+IGF-1) and Group C without growth factor as negative control.
2015-04-30 | E-GEOD-60060 | biostudies-arrayexpress
Project description:We have previously reported that the deficiency of p53 alone or in combination with Rb (Rb-/- p53-/-) in adipose-derived MSCs (ASCs) promotes leiomyosarcoma-like tumors in vivo. Here, we hypothesized that the source of MSCs and/or the cell differentiation stage could determine the phenotype of sarcoma development. To investigate whether there is a link between the source of MSCs and sarcoma phenotype, we generated p53-/- and Rb-/-p53-/- MSCs from bone marrow (BM-MSCs). Both genotypes of BM-MSCs initiated leiomyosarcoma formation similar to p53-/- and Rb-/-p53-/- ASCs. In addition, gene expression profiling revealed a link between p53- or Rb-p53-deficient BM-MSCs and ASCs and muscle-associated sarcomagenesis. These data suggest that the tissue source of MSC does not seem a crucial factor in the development of a particular sarcoma phenotype. To analyze whether the differentiation stage defines the sarcoma phenotype, BM-MSCs and ASCs were induced to differentiate towards the osteogenic lineage, and both p53 and Rb were excised using Cre-expressing adenovectors at different stages along osteogenic differentiation. Regardless of the level of osteogenic commitment, the inactivation of Rb and p53 in BM-MSC-derived, but not in ASC-derived, osteogenic progenitors gave rise to osteosarcoma-like tumors which could be serially transplanted. This indicates that the osteogenic differentiation stage of BM-MSCs imposes the phenotype of in vivo sarcoma development, and that BM-MSC-derived osteogenic progenitors rather than undifferentiated BM-MSCs, undifferentiated ASCs or ASC-derived osteogenic progenitors, represent the cell of origin for osteosarcoma development. To analyse whether the BM-MSC and Fat-MSC (ASC) differentiation stage may define the sarcoma phenotype, RbloxP/loxPp53loxP/loxP BM-MSCs and ASCs were induced to differentiate towards the osteogenic lineage and both Rb and p53 were excised with adenoviral vectors expressing the Cre-recombinase gene (Ad-CMV-Cre) at different stages (day 0 and 10) along osteogenic differentiation. NSG mice were inoculated subcutaneously with 5M-CM-^W10^6 mutant cells. Animals were killed when tumors reached 1 cm3 or 150 days after infusion. Some of the obtained tumors were mechanically disaggregated to establish ex vivo MSC-transformed cell lines. Gene expression analysis was performed using: WT BM-MSCs and ASCs, Rb-/-p53-/- BM-MSCs and ASCs previously differentiated to the osteogenic lineage for 10 days and a tumor cell line derived from p53-/-Rb-/- BM-MSC differentiated to the osteogenic lineage for 10 days.
2013-01-28 | E-GEOD-43803 | biostudies-arrayexpress