msc immunomodulation mir

INTRODUCTION: Mesenchymal stromal cells (MSC) are one of the main cellular components of bone marrow (BM) microenvironment. MSC play a key role in tissue regeneration, but they are also capable of immunomodulating activity. With host aging, MSC undergo age-related changes, which alter these functions, contributing to the set-up of "inflammaging", which is known to be the basis for the development of several diseases of the elderly, including cancer. However, there's few data investigating this facet of MSC, mainly obtained using murine models or replicative senescence...

Rationale: In the bone marrow microenvironment (BMME), mesenchymal stem/stromal cells (MSCs) control the self-renewal of both healthy and cancerous hematopoietic stem/progenitor cells (HSPCs). We previously showed that in vivo leukemia-derived MSCs change neighbor MSCs into leukemia-permissive states and boost leukemia cell proliferation, survival, and chemotherapy resistance. But the mechanisms behind how the state changes are still not fully understood. Methods: Here, we took a reverse engineering approach to determine BCR-ABL1+ leukemia cells activated transcriptional factor C/EBPβ, resulting in miR130a/b-3p production...

Background: Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have been increasingly proved as promising immunomodulators against some autoimmune disorders. However, the possible effect and the underlying mechanism of MSC-sEVs in autoimmune dry eye have been rarely studied. Methods: Small extracellular vesicles from human umbilical cord mesenchymal stem cells (hUC-MSC-sEVs) were subconjunctivally injected to rabbit dry eye model, and their preventive or therapeutical effects were assessed by recording the clinical and histological scores...

Recent research indicated that extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) are a promising alternative to MSCs for immunomodulatory therapy. However, the contents of MSC-EVs would change as their parent MSCs change, hence the therapeutic efficacy of MSC-derived EVs (MSC-EVs) would largely depend on donors, tissue sources and culture conditions of MSCs. To overcome limitations of tissue-derived MSCs, we previously used MSCs derived from human induced pluripotent stem cells (iMSCs) to produce EVs and demonstrated their therapeutic potential in a mouse model of secondary Sjo¨gren's Syndrome...

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Cell therapy limits ischemic injury following myocardial infarction (MI) by preventing cell death, modulating the immune response, and promoting tissue regeneration. The therapeutic efficacy of cardiosphere-derived cells (CDCs) and mesenchymal stem cells (MSCs) is associated with extracellular vesicle (EV) release. Prior head-to-head comparisons have shown CDCs to be more effective than MSCs in MI models. Despite differences in cell origin, it is unclear why EVs from different adult stem cell populations elicit differences in therapeutic efficacy...

AIMS: The balance between various CD4+ T cell subsets through highly regulated differentiation of naïve T cells is critical to ensure proper immune response, disruption of which may cause autoimmunity and cancers. miR-10a has been reported to regulate the fate of naïve T cells. Mesenchymal stem cells (MSC) derived exosomes are known effective immunomodulators and ideal vehicles for delivery of microRNAs. This study was aimed to examine the impacts of miR-10a on CD4+ cell fate upon exosomal delivery in combination with immunomodulatory effects of MSCs...

Bone marrow mesenchymal stem cells (MSCs) have demonstrated therapeutic effects for colitis through immunomodulation and anti-inflammation. However, whether MSC-derived exosomes possessed the similar function remains unclear. In present study, exosomes were isolated from control and IFN-γ-primed MSCs and was verified by transmission electron microscope (TEM) and immunofluorescence staining. Administration of exosomes to mice significantly improved the disease activity index and histological score of colitis, and decreased the ratio of Th17 cells with elevated Treg cells ratio in mice colitis model...

Mesenchymal stem cells (MSCs) have emerged as a cell-based therapy in many diseases including atherosclerosis (AS) due to their capability of immunomodulation and tissue regeneration. However, the pathway for MSCs' antiatherosclerotic activity remains to be elucidated. Here, we test the hypothesis that microRNA-221 (miR-221) from MSC-derived extracellular vesicles (EVs) alleviates AS. Male ApoE-/- mice were fed a high-fat diet for 12 weeks to induce AS, and were then treated with human bone marrow mesenchymal stem cell-derived EVs by tail vein injection...

PURPOSE: Our hypothesis is that human adipose mesenchymal stem cell (MSC)-derived extracellular vesicle (EV) can be used as a delivery platform for microRNAs to effectively attenuate lung ischemia-reperfusion injury (IRI). METHODS: C57Bl/6 (WT) mice underwent sham or lung IRI (1hr of ischemia followed by 2hr reperfusion using left lung hilar-ligation model) with or without treatment (1hr prior to ischemia) with EVs or antagomiR-206 enriched EVs (3x106 EVs given intratracheally; n=5/group)...

Accumulating evidence indicates that mesenchymal stem/stromal cell-derived extracellular vesicles (MSC-EVs) exhibit immunomodulatory effects by delivering therapeutic RNAs and proteins; however, the molecular mechanism underlying the EV-mediated immunomodulation is not fully understood. In this study, we found that EVs from early-passage MSCs had better immunomodulatory potency than did EVs from late-passage MSCs in T cell receptor (TCR)- or Toll-like receptor 4 (TLR4)-stimulated splenocytes and in mice with ocular Sjögren's syndrome...

OBJECTIVE: Mesenchymal stem cells (MSCs), one of the most important stromal cells in the tumor microenvironment, play a major role in the immunomodulation and development of tumors. In contrast to immunomodulatory effects of bone marrow-derived MSCs, resident MSCs were not well studied in tumor. The aim of this study was to compare the immunomodulatory properties and protein secretion profiles of MSCs isolated from breast tumor (T-MSC) and normal breast adipose tissue (N-MSC). MATERIALS AND METHODS: T-MSCs and N-MSCs were isolated by the explant culture method and characterized, and their immunomodulatory function was assessed on peripheral blood lymphocytes (PBLs) by evaluating the effects of MSC conditioned media on the proliferation and induction of some cytokines and regulatory T cells (Tregs) by BrdU assay, ELISA, and flow cytometry...

AIMS: Mesenchymal stromal cells (MSCs) gradually become attractive candidates for cardiac inflammation modulation, yet understanding of the mechanism remains elusive. Strikingly, recent studies indicated that exosomes secreted by MSCs might be a novel mechanism for the beneficial effect of MSCs transplantation after myocardial infarction. We therefore explored the role of MSC-derived exosomes (MSC-Exo) in the immunomodulation of macrophages after myocardial ischaemia/reperfusion (I/R) and its implications in cardiac injury repair...

Immunomodulatory or immunosuppressive properties of bone marrow-derived mesenchymal stem cells (BM-MSCs) facilitate the treatment of acute respiratory distress syndrome and acute lung injury (ALI). Dysregulated miRNA (miRNA or miR) expression associated with the effects of BM-MSCs was assessed in a rat model of lipopolysaccharide (LPS)-induced ALI. The present study performed biochemical tests to assess five analytes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate, blood urea nitrogen (BUN), and creatinine (CREA)...

The formation of an abdominal aortic aneurysm (AAA) is characterized by inflammation, macrophage infiltration, and vascular remodeling. In this study, we tested the hypothesis that mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) immunomodulate aortic inflammation, to mitigate AAA formation via modulation of microRNA-147. An elastase-treatment model of AAA was used in male C57BL/6 wild-type (WT) mice. Administration of EVs in elastase-treated WT mice caused a significant attenuation of aortic diameter and mitigated proinflammatory cytokines, inflammatory cell infiltration, an increase in smooth muscle cell α-actin expression, and a decrease in elastic fiber disruption, compared with untreated mice...