Mesenchymal stem cell-derived exosomal microRNA-367–3p alleviates experimental autoimmune encephalomyelitis via inhibition of microglial ferroptosis by targeting EZH2

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 162, P. 114593 - 114593

Published: March 29, 2023

Multiple sclerosis (MS) is an autoimmune, inflammatory demyelinating disorder of the central nervous system. Accumulating evidence has underscored therapeutic potential bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-Exos) containing bioactive compounds in MS. Herein, current study sought to characterize mechanism BMSC-Exos harboring miR-367-3p both BV2 microglia by Erastin-induced ferroptosis and experimental autoimmune encephalomyelitis (EAE), a typical animal model Exosomes were firstly isolated from BMSCs identified for further use. co-cultured with miR-367-3p-containing BMSC-Exos, followed assessment cell ferroptosis. Mechanistic exploration was furthered interaction its downstream regulators. Lastly, injected into EAE mice vivo validation. carrying restrained microglial vitro. Mechanistically, could bind Enhancer zeste homolog 2 (EZH2) restrain EZH2 expression, leading over-expression solute carrier family 7 member 11 (SLC7A11). Meanwhile, SLC7A11 resulted Glutathione Peroxidase 4 (GPX4) activation suppression. Ectopic expression vitro negated protective effects BMSC-Exos. Furthermore, relieved severity suppressing restraining vivo. Collectively, our findings suggest that brings about significant decline repressing alleviating vivo, suggesting possible role overexpression treatment strategy EAE. AVAILABILITY OF DATA AND MATERIALS: The datasets used and/or analyzed during are available corresponding author upon reasonable request.

Language: Английский

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An Effective Peptide-Based Platform for Efficient Exosomal Loading and Cellular Delivery of a microRNA

ACS Applied Materials & Interfaces, Journal Year: 2023, Volume and Issue: 15(3), P. 3851 - 3866

Published: Jan. 13, 2023

Exosomes, membrane-bound nanosized vesicles of biologic origin, are known to contain various molecules, e.g., proteins, lipids, and nucleic acids, which contribute the exosomes' ability mediate cell-to-cell communication. Recent impediments artificial nanoparticles in drug delivery, including low cellular uptake, activation immune system, tissue obstacles, have led scientists engineer exosomes as delivery vehicles. Though possess inherent properties stability, biocompatibility, immunogenicity, capability cross biological barriers, there is a need develop technologies that allow efficient loading therapeutic materials into exosomes. Here, we introduced simple peptide-equipped technology can enhance cargo-loading potential mild environment. Specifically, cell-penetrating peptide, YARA, derived from human immunodeficiency virus-1 trans-activator transcription, was covalently conjugated with miR-21-5p, mammalian microRNA. The conjugate YARA-miR-21-5p then incubated exosomes, isolated either mesenchymal stem cells or cancer cells, for loading. Exosomal time-dependent demonstrated an impressive 18.6-fold increase efficiency over exosomal miR-21-5p through incubation. After effective loaded rapidly delivered cells. Relative unloaded free YARA-miR-21-5p, significantly enhanced proliferation, migration, invasion mouse fibroblasts, vital steps wound healing. This study lays groundwork using peptides innovative approach efficiently load cargos, microRNAs, be employed deliver cargos yield effects.

Language: Английский

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Proteomic profiling of mesenchymal stem cell‐derived extracellular vesicles: Impact of isolation methods on protein cargo

Journal of Extracellular Biology, Journal Year: 2024, Volume and Issue: 3(6)

Published: June 1, 2024

Abstract Extracellular vesicles (EVs) are nanosized with a lipid bilayer that secreted by cells and play critical role in cell‐to‐cell communication. Despite the promising reports regarding their diagnostic therapeutic potential, utilization of EVs clinical setting is limited due to insufficient information about cargo lack standardization isolation analysis methods. Considering protein cargos as key contributors potency, we conducted tandem mass tag (TMT) quantitative proteomics three subpopulations mesenchymal stem cell (MSC)‐derived obtained through different techniques: ultracentrifugation (UC), high‐speed centrifugation (HS), on sucrose cushion (SU). Subsequently, checked EV marker expression, size distribution, morphological characterization, followed bioinformatic analysis. The proteome results revealed these exhibit distinct molecular functional characteristics. choice method impacts isolated isolating EVs. Specifically, (HS) exhibited higher abundance ribosomal mitochondrial proteins. Functional apoptosis assays comparing mitochondria methods HS‐EVs, but not other EVs, induced early cancer cells. On hand, using (SU) (UC) demonstrated proteins primarily involved immune response, cell‐cell interactions extracellular matrix interactions. Our analyses unveil notable disparities associated biological functions among subpopulations, underscoring importance meticulously selecting resultant based intended application.

Language: Английский

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Nanotechnology and bioengineering approaches to improve the potency of mesenchymal stem cell as an off‐the‐shelf versatile tumor delivery vehicle

Medicinal Research Reviews, Journal Year: 2024, Volume and Issue: 44(4), P. 1596 - 1661

Published: Feb. 1, 2024

Abstract Targeting actionable mutations in oncogene‐driven cancers and the evolution of immuno‐oncology are two prominent revolutions that have influenced cancer treatment paradigms caused emergence precision oncology. However, intertumoral intratumoral heterogeneity main challenges both fields treatment. In other words, finding a universal marker or pathway patients suffering from particular type is challenging. Therefore, targeting single hallmark with targeted therapeutic will not be efficient for fighting against tumor heterogeneity. Mesenchymal stem cells (MSCs) possess favorable characteristics cellular therapy, including their hypoimmune nature, inherent tumor‐tropism property, straightforward isolation, multilineage differentiation potential. MSCs can loaded various chemotherapeutics oncolytic viruses. The combination these intrinsic features possibility genetic manipulation makes them versatile delivery vehicle used vivo selective chemotherapeutic biological therapeutics. as biofactory local production chemical anticancer agents at site. MSC‐mediated immunotherapy could facilitate sustained release immunotherapeutic specifically site, allow achievement concentrations without need repetitive systemic administration high doses. Despite enthusiasm evoked by preclinical studies MSC therapy approaches, translation into clinical applications has faced serious challenges. This manuscript, critical viewpoint, reviewed evaluated tool gene immunotherapy, chemotherapy. Then, novel nanotechnology bioengineering approaches improve potency overcoming related to low localization sites discussed.

Language: Английский

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Profiles of Exosomal microRNAs in Joint Cells and Candidate microRNAs for Cartilage Regeneration

Tissue Engineering Part A, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

The activation of chondrogenic progenitor cells (CPCs) in articular cartilage during a traumatic injury is vital for regeneration. Although our understanding the mechanisms underlying CPC remains incomplete, there evidence that exosomal microRNAs (miRNAs or miRs) are involved tissue healing due to their regulating role posttranscriptional gene expressions. In this study, we profiled enriched and differential expression miRNAs exosomes derived from bovine joint (CPCs, chondrocytes, synoviocytes) via Next Generation Sequencing analysis validated potential therapeutic effects candidate For CPC-based regeneration, tested impact administering miR-107, miR-140, miR-148a on CPCs because found these were highly differentially expressed chondrocytes-derived (CC-Exo). We that: (1) miR-140 induced including SRY-box transcription factor 9, collagen type 2A1, aggrecan, (2) miR-107 suppressed catabolic matrix metalloproteinase 3, disintegrin with thrombospondin motifs 5, nitric oxide synthase 2. Our findings indicate transfection specific present CC-Exo have promote regeneration could be an important component posttraumatic osteoarthritis prevention.

Language: Английский

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Nanotechnology to Overcome Blood–Brain Barrier Permeability and Damage in Neurodegenerative Diseases

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(3), P. 281 - 281

Published: Feb. 20, 2025

The blood–brain barrier (BBB) is a critical structure that maintains brain homeostasis by selectively regulating nutrient influx and waste efflux. Not surprisingly, it often compromised in neurodegenerative diseases. In addition to its involvement these pathologies, the BBB also represents significant challenge for drug delivery into central nervous system. Nanoparticles (NPs) have been widely explored as carriers capable of overcoming this effectively transporting therapies brain. However, their potential directly address ameliorate dysfunction has received limited attention. review, we examine how NPs enhance across treat diseases explore emerging strategies restore integrity vital structure.

Language: Английский

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Mesenchymal stem cell-derived exosomes as a plausible immunomodulatory therapeutic tool for inflammatory diseases

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 10, 2025

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), especially, exosomes are considered to have diverse therapeutic effects for various significant diseases. MSC-derived (MSCex) offer substantial advantages over MSCs due their long-term preservation, stability, absence of nuclei and fewer adverse such as infusion toxicity, thereby paving the way towards regenerative medicine cell-free therapeutics. These harbor several cellular contents DNA, RNA, lipids, metabolites, proteins, facilitating drug delivery intercellular communication. MSCex ability immunomodulate trigger anti-inflammatory process hence, playing a key role in alleviating inflammation enhancing tissue regeneration. In this review, we addressed underlying immunomodulatory pathways. Moreover, discussed recent updates on treating specific inflammatory diseases, including arthritis, bowel disease, eye respiratory diseases asthma acute distress syndrome (ARDS), well neurodegenerative cardiac Finally, highlighted challenges using successful tool future perspectives.

Language: Английский

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The Emerging Role of Exosomes in Oral Squamous Cell Carcinoma

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Feb. 22, 2021

Oral cancer constitutes approximately 2% of all cancers, while the most common type, oral squamous cell carcinoma (OSCC) represents 90% cancers. Although treatment OSCC has improved recently, it still a high rate local recurrence and poor prognosis, with 5-year survival only 50%. Advanced stage tends to metastasize lymph nodes. Thus, exploring new therapeutic strategies for is therefore an urgent priority. Exosomes, small membrane vesicles derived from endosomes, have been detected in wide array bodily fluids. Exosomes contain diversity proteins, mRNAs, non-coding RNAs, including microRNAs, long piRNAs, circular tsRNAs, ribosomal which are delivered neighboring cells or even transported distant sites. associated tumorigenesis OSCC, promote proliferation, colonization, metastasis by transferring their contents target cells. Furthermore, exosomes involved regulation tumor microenvironment transform conditions favoring progression vivo . In this review, we summarize crucial role discuss potential clinical application treatment.

Language: Английский

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Placenta-Derived MicroRNAs in the Pathophysiology of Human Pregnancy

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: March 11, 2021

In placental mammals, reproductive success, and maternal-fetal health substantially depend on a well-being placenta, the interface between fetus mother. Disorders in cells are tightly associated with adverse pregnancy outcomes including preeclampsia (PE), fetal growth restriction, etc. MicroRNAs (miRNAs) represent small non-coding RNAs that regulate post-transcriptional gene expression integral to wide range of healthy or diseased cellular proceedings. Numerous miRNAs have been detected human placenta increasing evidence is revealing their important roles regulating cell behaviors. Recent studies indicate placenta-derived can be released maternal circulation via encapsulating into exosomes, they potentially target various provide hormone-like means intercellular communication mother fetus. These exosome attracting more attention due differential pregnant complications, which may novel biomarkers for prediction diseases. this review, we briefly summarize current knowledge perspectives miRNAs, especially exosomal transfer pathophysiological relevance PE. The possible exosomal-miRNA-targeted strategies diagnosis, prognosis therapy PE highlighted.

Language: Английский

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Upregulation of miR-96-5p by bone marrow mesenchymal stem cells and their exosomes alleviate non-alcoholic steatohepatitis: Emphasis on caspase-2 signaling inhibition

Biochemical Pharmacology, Journal Year: 2021, Volume and Issue: 190, P. 114624 - 114624

Published: May 27, 2021

Language: Английский

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