Browse
Submit Data
Databases
API
Help

Dataset Information

31 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mesenchymal stem cell-derived extracellular vesicles may promote breast cancer cell dormancy.

ABSTRACT: Disseminated breast cancer cells have the capacity to metastasise to the bone marrow and reside in a dormant state within the mesenchymal stem cell niche. Research has focussed on paracrine signalling factors, such as soluble proteins, within the microenvironment. However, it is now clear extracellular vesicles secreted by resident mesenchymal stem cells into this microenvironment also play a key role in the initiation of dormancy. Dormancy encourages reduced cell proliferation and migration, while upregulating cell adhesion, thus retaining the cancer cells within the bone marrow microenvironment. Here, MCF7 breast cancer cells were treated with mesenchymal stem cell-derived extracellular vesicles, resulting in reduced migration in two-dimensional and three-dimensional culture, with reduced cell proliferation and enhanced adhesion, collectively supporting cancer cell dormancy.

SUBMITTER: Casson J

PROVIDER: S-EPMC6311537 | biostudies-literature | 2018 Jan-Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Mesenchymal stem cell-derived extracellular vesicles may promote breast cancer cell dormancy.

Casson Jake J Davies Owen G OG Smith Carol-Anne CA Dalby Matthew J MJ Berry Catherine C CC

Journal of tissue engineering 20180101

Disseminated breast cancer cells have the capacity to metastasise to the bone marrow and reside in a dormant state within the mesenchymal stem cell niche. Research has focussed on paracrine signalling factors, such as soluble proteins, within the microenvironment. However, it is now clear extracellular vesicles secreted by resident mesenchymal stem cells into this microenvironment also play a key role in the initiation of dormancy. Dormancy encourages reduced cell proliferation and migration, wh ...[more]

PMID: 30627418

Similar Datasets

Mesenchymal Stromal/stem Cell-derived Extracellular Vesicles Promote Human Cartilage Regeneration In Vitro.

Project description:Osteoarthritis (OA) is a rheumatic disease leading to chronic pain and disability with no effective treatment available. Recently, allogeneic human mesenchymal stromal/stem cells (MSC) entered clinical trials as a novel therapy for OA. Increasing evidence suggests that therapeutic efficacy of MSC depends on paracrine signalling. Here we investigated the role of extracellular vesicles (EVs) secreted by human bone marrow derived MSC (BMMSC) in human OA cartilage repair. METHODS:To test the effect of BMMSC-EVs on OA cartilage inflammation, TNF-alpha-stimulated OA chondrocyte monolayer cultures were treated with BMMSC-EVs and pro-inflammatory gene expression was measured by qRT-PCR after 48 h. To assess the impact of BMMSC-EVs on cartilage regeneration, BMMSC-EVs were added to the regeneration cultures of human OA chondrocytes, which were analyzed after 4 weeks for glycosaminoglycan content by 1,9-dimethylmethylene blue (DMMB) assay. Furthermore, paraffin sections of the regenerated tissue were stained for proteoglycans (safranin-O) and type II collagen (immunostaining). RESULTS:We show that BMMSC-EVs inhibit the adverse effects of inflammatory mediators on cartilage homeostasis. When co-cultured with OA chondrocytes, BMMSC-EVs abrogated the TNF-alpha-mediated upregulation of COX2 and pro-inflammatory interleukins and inhibited TNF-alpha-induced collagenase activity. BMMSC-EVs also promoted cartilage regeneration in vitro. Addition of BMMSC-EVs to cultures of chondrocytes isolated from OA patients stimulated production of proteoglycans and type II collagen by these cells. CONCLUSION:Our data demonstrate that BMMSC-EVs can be important mediators of cartilage repair and hold great promise as a novel therapeutic for cartilage regeneration and osteoarthritis.

| S-EPMC5817101 | biostudies-literature

Mesenchymal Stem Cell Derived Extracellular Vesicles in Aging.

Project description:Aging is associated with high prevalence of chronic degenerative diseases that take a large part of the increasing burden of morbidities in a growing demographic of elderly people. Aging is a complex process that involves cell autonomous and cell non-autonomous mechanisms where senescence plays an important role. Senescence is characterized by the loss of proliferative potential, resistance to cell death by apoptosis and expression of a senescence-associated secretory phenotype (SASP). SASP includes pro-inflammatory cytokines and chemokines, tissue-damaging proteases, growth factors; all contributing to tissue microenvironment alteration and loss of tissue homeostasis. Emerging evidence suggests that the changes in the number and composition of extracellular vesicles (EVs) released by senescent cells contribute to the adverse effects of senescence in aging. In addition, age-related alterations in mesenchymal stem/stromal cells (MSCs) have been associated to dysregulated functions. The loss of functional stem cells necessary to maintain tissue homeostasis likely directly contributes to aging. In this review, we will focus on the characteristics and role of EVs isolated from senescent MSCs, the potential effect of MSC-derived EVs in aging and discuss their therapeutic potential to improve age-related diseases.

| S-EPMC7047768 | biostudies-literature

Therapeutic roles of mesenchymal stem cell-derived extracellular vesicles in cancer.

Project description:Extracellular vesicles (EVs) are cell-derived membrane structures enclosing proteins, lipids, RNAs, metabolites, growth factors, and cytokines. EVs have emerged as essential intercellular communication regulators in multiple physiological and pathological processes. Previous studies revealed that mesenchymal stem cells (MSCs) could either support or suppress tumor progression in different cancers by paracrine signaling via MSC-derived EVs. Evidence suggested that MSC-derived EVs could mimic their parental cells, possessing pro-tumor and anti-tumor effects, and inherent tumor tropism. Therefore, MSC-derived EVs can be a cell-free cancer treatment alternative. This review discusses different insights regarding MSC-derived EVs' roles in cancer treatment and summarizes bioengineered MSC-derived EVs' applications as safe and versatile anti-tumor agent delivery platforms. Meanwhile, current hurdles of moving MSC-derived EVs from bench to bedside are also discussed.

| S-EPMC8414028 | biostudies-literature

Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Promote Neuroprotection in Rodent Models of Glaucoma.

Project description:PurposeTo investigate the benefit of bone marrow mesenchymal stem cell (BMSC)-derived small extracellular vesicles (sEV) as an intravitreal (ivit) therapy in two rat models of glaucoma and to determine and identify candidate miRNA involved in the mechanism.MethodssEV were isolated from human BMSC and fibroblasts and ivit injected into adult rats after induction of elevated IOP. IOP was elevated using either intracameral injection of microbeads or laser photocoagulation of circumferential limbal vessels and the trabecular meshwork. Retinal nerve fiber layer (RNFL) thickness was measured using optical coherence tomography, positive scotopic threshold response (pSTR) recorded using ERG, and RNA binding protein with multiple splicing (RBPMS+) retinal ganglion cell (RGC) counted using retinal wholemounts. sEV miRNA were sequenced using RNAseq.ResultssEV isolated from BMSC promoted significant neuroprotection of RGC while preventing RNFL degenerative thinning and loss of pSTR. sEV proved therapeutically efficacious when ivit injected every week or every month, but ineffective with longer delays between treatments. Knockdown of Argonaute2 (AGO2), a protein critical for miRNA function and packing into sEV prior to sEV isolation, significantly attenuated the above effects. Addition of BMSC sEV (but not fibroblast sEV) reduced death of cultured purified RGC. RNAseq identified 43 miRNA upregulated in BMSC sEV in comparison to fibroblast sEV, which yielded no neuroprotective effects.ConclusionsInjection of BMSC-derived sEV into the vitreous provided significant therapeutic benefit to glaucomatous eyes. The neuroprotective effect of sEV, at least partially, may be explained by direct action on RGC through miRNA-dependent mechanisms.

| S-EPMC5795911 | biostudies-literature

Mesenchymal stem cell-derived extracellular vesicles attenuate kidney inflammation.

Project description:Mesenchymal stem/stromal cells (MSCs) have distinct capability for renal repair, but may have safety concerns. MSC-derived extracellular vesicles emerged as a novel noncellular alternative. Using a porcine model of metabolic syndrome and renal artery stenosis we tested whether extracellular vesicles attenuate renal inflammation, and if this capacity is mediated by their cargo of the anti-inflammatory cytokine interleukin (IL) 10. Pigs with metabolic syndrome were studied after 16 weeks of renal artery stenosis untreated or treated four weeks earlier with a single intrarenal delivery of extracellular vesicles harvested from adipose tissue-derived autologous MSCs. Lean and sham metabolic syndrome animals served as controls (seven each). Five additional pigs with metabolic syndrome and renal artery stenosis received extracellular vesicles with pre-silenced IL10 (IL10 knock-down). Single-kidney renal blood flow, glomerular filtration rate, and oxygenation were studied in vivo and renal injury pathways ex vivo. Retention of extracellular vesicles in the stenotic kidney peaked two days after delivery and decreased thereafter. Four weeks after injection, extracellular vesicle fragments colocalized with stenotic-kidney tubular cells and macrophages, indicating internalization or fusion. Extracellular vesicle delivery attenuated renal inflammation, and improved medullary oxygenation and fibrosis. Renal blood flow and glomerular filtration rate fell in metabolic syndrome and renal artery stenosis compared to metabolic syndrome, but was restored in pigs treated with extracellular vesicles. These renoprotective effects were blunted in pigs treated with IL10-depleted extracellular vesicles. Thus, extracellular vesicle-based regenerative strategies might be useful for patients with metabolic syndrome and renal artery stenosis.

| S-EPMC5483390 | biostudies-literature

Mesenchymal Stem Cell-Derived Extracellular Vesicles in Tissue Regeneration.

Project description:Mesenchymal stem cells (MSCs) are multipotent stem cells that have attracted increasing interest in the field of regenerative medicine. Previously, the differentiation ability of MSCs was believed to be primarily responsible for tissue repair. Recent studies have shown that paracrine mechanisms play an important role in this process. MSCs can secrete soluble molecules and extracellular vesicles (EVs), which mediate paracrine communication. EVs contain large amounts of proteins and nucleic acids, such as mRNAs and microRNAs (miRNAs), and can transfer the cargo between cells. The cargoes are similar to those in MSCs and are not susceptible to degradation due to the protection of the EV bimolecular membrane structure. MSC-EVs can mimic the biological characteristics of MSCs, such as differentiation, maturation, and self-renewal. Due to their broad biological functions and their ability to transfer molecules between cells, EVs have been intensively studied by an increasing number of researchers with a focus on therapeutic applications, especially those of EVs secreted by MSCs. In this review, we discuss MSC-derived EVs and their therapeutic potential in tissue regeneration.

| S-EPMC7444208 | biostudies-literature

Dendritic Cell-derived Extracellular Vesicles mediate Mesenchymal Stem/Stromal Cell recruitment.

Project description:Orchestration of bone repair processes requires crosstalk between different cell populations, including immune cells and mesenchymal stem/stromal cells (MSC). Extracellular vesicles (EV) as mediators of these interactions remain vastly unexplored. Here, we aimed to determine the mechanism of MSC recruitment by Dendritic Cells (DC), hypothesising that it would be mediated by EV. Primary human DC-secreted EV (DC-EV), isolated by ultracentrifugation, were characterized for their size, morphology and protein markers, indicating an enrichment in exosomes. DC-EV were readily internalized by human bone marrow-derived MSC, without impacting significantly their proliferation or influencing their osteogenic/chondrogenic differentiation. Importantly, DC-EV significantly and dose-dependently promoted MSC recruitment across a transwell system and enhanced MSC migration in a microfluidic chemotaxis assay. DC-EV content was analysed by chemokine array, indicating the presence of chemotactic mediators. Osteopontin and matrix metalloproteinase-9 were confirmed inside EV. In summary, DC-EV are naturally loaded with chemoattractants and can contribute to cell recruitment, thus inspiring the development of new tissue regeneration strategies.

| S-EPMC5431789 | biostudies-literature

Mesenchymal Stem Cell-Derived Extracellular Vesicles and Their Therapeutic Potential.

Project description:Extracellular vesicles (EVs) are cell-derived membrane-bound nanoparticles, which act as shuttles, delivering a range of biomolecules to diverse target cells. They play an important role in maintenance of biophysiological homeostasis and cellular, physiological, and pathological processes. EVs have significant diagnostic and therapeutic potentials and have been studied both in vitro and in vivo in many fields. Mesenchymal stem cells (MSCs) are multipotent cells with many therapeutic applications and have also gained much attention as prolific producers of EVs. MSC-derived EVs are being explored as a therapeutic alternative to MSCs since they may have similar therapeutic effects but are cell-free. They have applications in regenerative medicine and tissue engineering and, most importantly, confer several advantages over cells such as lower immunogenicity, capacity to cross biological barriers, and less safety concerns. In this review, we introduce the biogenesis of EVs, including exosomes and microvesicles. We then turn more specifically to investigations of MSC-derived EVs. We highlight the great therapeutic potential of MSC-derived EVs and applications in regenerative medicine and tissue engineering.

| S-EPMC7463378 | biostudies-literature

Clinical potential of mesenchymal stem/stromal cell-derived extracellular vesicles.

Project description:Within the last two decades mesenchymal stem/stromal cells (MSCs) emerged after hematopoietic stem cells as the second most investigated and applied somatic stem cell entity so far. MSCs mediate immunosuppressive as well as pro-regenerative activities. Against the initial assumption, MSCs may not primarily exert their therapeutic functions in a cellular but rather in a paracrine manner. Here, extracellular vesicles (EVs), such as exosomes and microvesicles, have been identified as major mediators of these paracrine effects. Meanwhile, MSC-EVs have been applied to an increasing amount of different animal models and were tested in a patient suffering from steroid-refractory acute graft-versus-host disease (acute GvHD) as well as in a patient cohort with chronic kidney disease. So far, the MSC-EV administration appears to be safe in humans and all tested animal models. Improvements were reported in all settings. Thus, MSC-EVs appear as promising novel therapeutic agents which might help to improve disease associated symptoms in millions of patients. Here, we review some of the milestones in the field, briefly discuss challenges and highlight clinical aspects of acute GvHD and its treatment with MSCs and MSC-EVs.

| S-EPMC5676188 | biostudies-literature

Mesenchymal Stem Cell-Derived Extracellular Vesicles for Corneal Wound Repair.

Project description:With the immunoregulation potential, mesenchymal stem cells (MSCs) have been used for tissue regeneration by relieving inflammation in the injured tissues. When this repair process is interfered by immune disorders or pathological angiogenesis, the delays in corneal epithelial wound healing can lead to a persistent epithelial defect. Stem cell-derived extracellular vesicles (EVs), which carry abundant bioactive molecules from stem cells, have provided an alternative to regeneration therapy. In this study, we aimed to investigate if EVs from human placenta-derived MSCs (hP-MSCs) could ameliorate alkali injury of the cornea in the mouse model. 33.33??g/?L EVs in 10??L PBS were applied to the cornea. Repeat application three times, and 100??g EVs (in 30??L PBS) in total were administrated per day for two weeks. Our results revealed that EVs from hP-MSCs had preferable functions including enhancing proliferation and anti-inflammation and suppressing apoptosis of corneal epithelial cells. Furthermore, hP-MSC-derived EVs ameliorated mouse corneal wound healing by inhibiting angiogenesis and inflammation. Taken together, our current data suggested that hP-MSC-derived EVs have the beneficial effects of corneal wound healing, which provide alternative cell-free therapy with great practical value.

| S-EPMC6925772 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data