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Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cell(MSC)s effectively treat liver fibrosis (scRNA-seq)

ABSTRACT: Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cell(MSC)s effectively treat liver fibrosis (scRNA-seq)

PROVIDER: PRJNA705913 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13826333.fastq.gz	Fastqsanger.gz
	SRR13826334.fastq.gz	Fastqsanger.gz
	SRR13826335.fastq.gz	Fastqsanger.gz
	SRR13826336.fastq.gz	Fastqsanger.gz
	SRR13826337.fastq.gz	Fastqsanger.gz

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Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cell(MSC)s effectively treat liver fibrosis

Project description:Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cell(MSC)s effectively treat liver fibrosis

| PRJNA705354 | ENA

Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cell(MSC)s effectively treat liver fibrosis

Project description:A novel therapeutic approach of IFN-γ-treated mesenchymal stromal cell-produced extracellular vesicles effectively treated a cirrhosis model.

2021-02-28 | GSE167863 | GEO

Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cell(MSC)s effectively treat liver fibrosis (scRNA-seq)

Project description:A new therapeutic approach of IFN-γ-treated mesenchymal stromal cell-produced extracellular vesicles effectively treated a cirrhosis model.

2021-03-03 | GSE168042 | GEO

Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis.

Project description:Mesenchymal stromal cells (MSCs) are used for ameliorating liver fibrosis and aiding liver regeneration after cirrhosis; Here, we analyzed the therapeutic potential of small extracellular vesicles (sEVs) derived from interferon-γ (IFN-γ) pre-conditioned MSCs (γ-sEVs). γ-sEVs effectively induced anti-inflammatory macrophages with high motility and phagocytic abilities in vitro, while not preventing hepatic stellate cell (HSC; the major source of collagen fiber) activation in vitro. The proteome analysis of MSC-derived sEVs revealed anti-inflammatory macrophage inducible proteins (e.g., annexin-A1, lactotransferrin, and aminopeptidase N) upon IFN-γ stimulation. Furthermore, by enabling CX3CR1+ macrophage accumulation in the damaged area, γ-sEVs ameliorated inflammation and fibrosis in the cirrhosis mouse model more effectively than sEVs. Single cell RNA-Seq analysis revealed diverse effects, such as induction of anti-inflammatory macrophages and regulatory T cells, in the cirrhotic liver after γ-sEV administration. Overall, IFN-γ pre-conditioning altered sEVs resulted in efficient tissue repair indicating a new therapeutic strategy.

| S-EPMC8010072 | biostudies-literature

RNA-seq analysis of HD and MDS MSCs and MSC-conditioned monocytes

Project description:Altered bone marrow hematopoiesis and immune suppression is a hallmark of myelodysplastic syndrome (MDS). While the bone marrow microenvironment influences malignant hematopoiesis, the mechanism leading to MDS-associated immune suppression is unknown. We tested whether mesenchymal stromal cells (MSCs) contribute to this process. Here, we developed a model to study cultured MSCs from MDS patients compared to similar aged matched normal controls for regulation of immune function. MSCs from MDS patients (MDS-MSC) and healthy donor MSC (HD-MSC) exhibited a similar in vitro phenotype and neither had a direct effect on NK cell function. However, when MDS and HD-MSCs were cultured with monocytes, only the MDS-MSCs acquired phenotypic and metabolic properties of myeloid-derived suppressor cells (MDSCs), with resulting suppression of NK cell function, along with T cell proliferation. A unique MSC transcriptome was observed in MDS-MSCs compared to HD-MSCs, including increased expression of the reactive oxygen species (ROS) regulator, ENC1. High ENC1 expression in MDS-MSC induced suppressive monocytes with increased INHBA, a gene that encodes for a member of the TGF? superfamily of proteins. These monocytes also had reduced expression of the TGF? transcriptional repressor MAB21L2, further adding to their immune suppressive function. Silencing ENC1 or inhibiting ROS production in MDS-MSCs abrogated the suppressive function of MDS-MSC conditioned monocytes. In addition, silencing MAB21L2 in healthy MSC conditioned monocytes mimicked the MDS-MSC suppressive transformation of monocytes. Our data demonstrate that MDS-MSCs are responsible for inducing an immune suppressive microenvironment in MDS through an indirect mechanism involving monocytes.

2020-02-11 | GSE140101 | GEO

Gene expression profiling in IBD rat treat with MSC transplantation

Project description:Investigation of whole genome gene expression level changes in Inflammatory bowel disease rats after MSC transplantation, compared to IBD control rats, and to explore the mechanism of MSC transplantation. A four chip study using total RNA recovered from two separate IBD rats after MSC transplantation and two separate IBD control rats. Each chip measures the expression level of 26,419 genes from normal rat and IBD rat treated with MSC transplantation.

2015-05-08 | E-GEOD-68653 | biostudies-arrayexpress

Gene expression profiling in IBD rat treat with MSC transplantation

2015-05-08 | GSE68653 | GEO

RNA-seq analysis of HD and MDS MSCs and MSC-conditioned monocytes

Project description:RNA-seq analysis of HD and MDS MSCs and MSC-conditioned monocytes

| PRJNA588261 | ENA

Quantitative proteomic characterization of lung-MSC and bone marrow-MSC using DIA-mass spectrometry

Project description:Mesenchymal stromal cells (MSC) are ideal candidates for cell therapies, due to their immune-regulatory and regenerative properties. We have previously reported that lung-derived MSC are tissue-resident cells with lung-specific properties compared to bone marrow-derived MSC. Assessing relevant molecular differences between lung-MSC and bone marrow-MSC is important, given that such differences may impact their behavior and potential therapeutic use. Here, we present an in-depth mass spectrometry (MS) based strategy to investigate the proteomes of lung-MSC and bone marrow-MSC. The MS-strategy relies on label free quantitative data-independent acquisition (DIA) analysis and targeted data analysis using a MSC specific spectral library. We identified several significantly differentially expressed proteins between lung-MSC and bone marrow-MSC within the cell layer (352 proteins) and in the conditioned medium (49 proteins). Bioinformatics analysis revealed differences in regulation of cell proliferation, which was functionally confirmed by decreasing proliferation rate through Cytochrome P450 stimulation. Our study reveals important tissue-specific differences within proteome and matrisome profiles between lung- and bone marrow-derived MSC that may influence their behavior and affect the clinical outcome when used for cell-therapy.

2018-10-18 | PXD006419 | Pride

Effect of MSC and MSC-derived extracellular vesicles on human blood coagulation

Project description:Mesenchymal stem cells (MSC) have emerged as potent therapeutic tool for a number of pathologies, including immune ones. However, unwelcome effects of MSC on the blood coagulation were revealed in some cases, which require more in-depth analysis. In this study, we explored the trombotic properties of human MSC from umbilical cord. We revealed strong procoagulant effects of umbilical cord MSC toward human and rat whole blood and platelets-free plasma using rotational thromboelastometry and thrombodynamics tests. The similar potentiation of clotting was demonstrated for MSC-derived extracellular vesicles (EV). In order to suggest approaches to avoid unwanted effects we studied the impact of heparin supplement on MSC/EV procoagulation properties. We found that therapeutic doses of unfractionated heparin injected in the patient's blood (administered in vivo) did not abrogate the procoagulant properties of MSC. Mass-spectrometry analysis of proteins of MSC and EV involved in coagulation-associated pathways was used to evaluate mechanisms of protrombotic effects.

2019-03-26 | PXD012768 | Pride

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