MiRNA expression microrarray of MSC grown on bone inducing scaffolds
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: Federica Viti
PROVIDER: E-MTAB-3441 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:This experiment investigates differences in miRNA expression between different populations of human mesenchymal stem cells (MSCs), which are a potential treatment for multiple sclerosis (MS). Previously it has been reported that MSCs derived from human olfactory mucosa (OM-MSCs) may be a better candidate for the treatment of MS than MSCs derived from bone marrow (BM-MSCs), due to a better ability to promote CNS myelination in vitro. In this study, miRNA profiling of OM-MSCs and BM-MSCs was undertaken to investigate the differences between these two cell types in relation to their prospective therapeutic use.
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Project description:Conventional treatments for inflammatory bowel disease (IBD) have multiple potential side effects. Therefore, alternative treatments are desperately needed. In the present study, we proposed a new therapeutic tool for the treatment of IBD in murine pre-clinical models by using MSC-Exos. We demonstrated that the infused MSC-Exos are immunotolerated by the host, which is convenient for a future clinical application of MSC-Exos in IBD. To understand the molecular basis mediating the anticolitic benefit of MSC-Exos, we performed proteomic analysis using iTRAQ technology to detect the protein expression profiles in MSC-Exos and the corresponding supernatants from their parent cell MSCs. Proteomic analysis revealed that MSC-Exos were enriched in proteins involved in regulating multiple biological processes associated with the anti-colitic benefit of MSC-Exos. Particularly, metallothionein-2 in MSC-Exos was required for the suppression of inflammatory responses in macrophages. Taken together, MSC-Exos are critical regulators of inflammatory responses and may be promising candidates for IBD treatment.
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Project description:The purpose of this study was to determine whether the serum condition affected the gene expression in mesenchymal stem cells (MSCs)over time. To that end, we compared gene expression in MSCs maintained in regular growth medium supplemented with fetal calf serum (FCS) for 10 passages with gene expression of MSCs cultured in the same conditions for 4 passages for 2 different donors (i.e. donor3 and donor4). Likewise, we compared gene expression in MSCs maintained in regular growth medium supplemented with autologous serum(AS) for 10 passages with gene expression of MSCs cultured in the same conditions for 4 passages for the same 2 donors (i.e. donor3 and donor4). MSCs were cultured in FCS- or AS-supplemented medium and were analyzed at passage 4 and at passage 10.
2004-12-08 | E-MEXP-215 | biostudies-arrayexpress
Project description:We have employed whole genome microarray expression profiling to identify genes that characterize different populations of human postnatal stem cells and reflect their potency MSC, Mab and MAPC cultures were established from at least three different donors and their transcriptome was assayed using the Agilent 4x44k whole human genome microarray; furthermore, the H9 ESC line from U of Wisconsin and MSC from Lonza were added for comparison MSC = Mesenchymal Stem Cells, MAPC= Multipotent Adult Progenitor Cells, Mab= Mesoangioblasts, ESC= Embryonic Stem Cells
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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.
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Project description:Human mesenchymal stem cells (MSC) display a high potential for the development of novel treatment strategies for cartilage repair. However, the pathways involved in their differentiation to functional and non hypertrophic chondrocytes remain largely unknown, despite the work on embryologic development and the identification of key growth factors including members of the TGFbeta, Hh, Wnt and FGF families. In this study, we asked if we could identify specific biological networks independently from the growth factor used (TGFbeta-3 or BMP-2). To address this question, we used DNA microarrays and performed large-scale expression profiling of MSC at different time points during their chondral differentiation. By comparing these data with those obtained during their differentiation into osteoblasts and adipocytes, we identified 318 genes specific for chondrogenesis. We distributed the selected genes in 5 classes according to their kinetic of expression and used the Ingenuity software in order to identify new biological networks. We could reconstruct 3 phases for chondral differentiation, characterized by functional pathways. The first phase corresponds to cell attachment and apoptosis prevention with the up-regulation of α5 integrins, BCL6, NFIL3, RGS2 and down-regulation of CTGF and CYR61. The second phase is characterized by a proliferation/differentiation step with the continuous expression of MAF, PGF, HGMA1 or NOTCH3, CHI3L1, WNT5A, LEPR. Finally, the last step of differentiation/hypertrophy is characterized by expression of DKK1, APOD/E, SERPINF1 and TIMP4. These data propose new pathways to understand the complexity of MSC differentiation to chondrocytes and new potential targets for cell therapy applied to cartilage repair. Experiment Overall Design: To identify genes involved in TGFbeta03/BMP2-induced chondrogenesis, MSC were isolated from human bone marrow aspirates by adherence to culture dishes and cultivated to passage 3. After induction of chondrogenic differentiation with BMP2 or TGFbeta-3, gene expression was determined by microarray hybridization after 1, 3, 7 and 21 days and compared to the undifferentiated MSC.
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Project description:This SuperSeries is composed of the following subset Series: GSE37065: Long-term culture associated gene expression changes in MSC [Affymetrix] GSE37066: Pluripotent Stem Cells Escape From Senescence-Associated DNA Methylation Changes [Illumina] GSE38806: Gene expression profiles of induced pluripotent mesenchymal stromal cells [Affymetrix] Refer to individual Series
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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.
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