Extracellular Vesicles in Organ Fibrosis: Mechanisms, Therapies, and Diagnostics

Cells, Год журнала: 2021, Номер 10(7), С. 1596 - 1596

Опубликована: Июнь 25, 2021

Fibrosis is the unrelenting deposition of excessively large amounts insoluble interstitial collagen due to profound matrigenic activities wound-associated myofibroblasts during chronic injury in diverse tissues and organs. It a highly debilitating pathology that affects millions people globally leads decreased function vital organs increased risk cancer end-stage organ disease. Extracellular vesicles (EVs) produced within wound environment have emerged as important vehicles for conveying pro-fibrotic signals between many cell types involved driving fibrotic response. On other hand, EVs from sources such stem cells, uninjured parenchymal circulation vitro vivo anti-fibrotic provided novel much-needed therapeutic options. Finally, body fluids individuals contain cargo components may utility fibrosis biomarkers, which could circumvent current obstacles measurement clinic, allowing stage, progression, or regression be determined manner accurate, safe, minimally-invasive, conducive repetitive testing. This review highlights rapid recent progress our understanding EV-mediated pathogenesis, therapy, staging lung, kidney, heart, liver, pancreas, skin.

Язык: Английский

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Defining therapeutic targets for renal fibrosis: Exploiting the biology of pathogenesis

Biomedicine & Pharmacotherapy, Год журнала: 2021, Номер 143, С. 112115 - 112115

Опубликована: Сен. 3, 2021

Renal fibrosis is a failed wound-healing process of the kidney tissue after chronic, sustained injury, which common pathway and pathological marker virtually every type chronic disease (CKD), regardless cause. However, there lack effective treatment specifically targeting against renal per se to date. The main feature massive activation proliferation fibroblasts excessive synthesis secretion extracellular matrix (ECM) deposited in interstitium, leading structural damage, impairment function, eventually end-stage disease. In this review, we summarize recent advancements regarding participation interaction many types residents infiltrated cells during fibrosis, attempt comprehensively discuss mechanism from cellular level conclude by highlighting novel therapeutic targets approaches for development new treatments patients with fibrosis.

Язык: Английский

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Hypoxic mesenchymal stem cell-derived extracellular vesicles ameliorate renal fibrosis after ischemia–reperfusion injure by restoring CPT1A mediated fatty acid oxidation

Stem Cell Research & Therapy, Год журнала: 2022, Номер 13(1)

Опубликована: Май 7, 2022

Abstract Background Renal fibrosis is a common pathological process of chronic kidney diseases induced by multiple factors. Hypoxic pretreatment mesenchymal stem cells can enhance the efficacy secreted extracellular vesicles (MSC-EVs) on various diseases, but it not clear whether they better improve renal fibrosis. The latest research showed that recovery fatty acid oxidation (FAO) reduce In this study, we aimed to examine hypoxic with MSC (Hypo-EVs) FAO restore and investigate underlying mechanism. Methods Hypo-EVs were isolated from hypoxia-pretreated human placenta-derived (hP-MSC), Norm-EVs hP-MSC cultured under normal conditions. We used ischemia–reperfusion (I/R)-induced model in vivo. mice injected PBS, Hypo-EVs, or immediately after surgery day 1 postsurgery. function, pathology, assessed for damage evaluation. For mechanistic exploration, (FAO), mitochondrial morphological alterations, ATP production mass proteins detected Mitochondrial membrane potential reactive oxygen species (ROS) investigated vitro. Results found confer superior therapeutic effect structure damage, restoration function reduction Meanwhile, enhanced restoring expression key rate-limiting enzyme carnitine palmitoyl-transferase 1A (CPT1A). Mechanistically, improvement homeostasis, characterized repaired structure, production, inhibition oxidative stress, increased potential, partially explains improving thus attenuating I/R damage. Conclusions suppress CPT1A-mediated FAO, which effects may be achieved through regulation homeostasis. Our findings provide further mechanism support development cell-free therapy

Язык: Английский

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Mesenchymal Stem Cell-Derived Extracellular Vesicles for Therapeutic Use and in Bioengineering Applications

Cells, Год журнала: 2022, Номер 11(21), С. 3366 - 3366

Опубликована: Окт. 25, 2022

Extracellular vesicles (EVs) are small lipid bilayer-delimited particles that naturally released from cells into body fluids, and therefore can travel convey regulatory functions in the distal parts of body. EVs transmit paracrine signaling by carrying over cytokines, chemokines, growth factors, interleukins (ILs), transcription nucleic acids such as DNA, mRNAs, microRNAs, piRNAs, lncRNAs, sn/snoRNAs, mtRNAs circRNAs; these to predecided destinations perform their functions. While mesenchymal stem (MSCs) have been shown improve healing facilitate treatments various diseases, allogenic use is often accompanied serious adverse effects after transplantation. MSC-produced less immunogenic serve an alternative cellular therapies transmitting or delivering biomaterials diseased areas This review article focused on understanding properties derived different types MSCs MSC–EV-based therapeutic options. The potential modern technologies 3D bioprinting advance EV-based also discussed.

Язык: Английский

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Bone mesenchymal stem cells-derived miR-223-3p-containing exosomes ameliorate lipopolysaccharide-induced acute uterine injury via interacting with endothelial progenitor cells

Bioengineered, Год журнала: 2021, Номер 12(2), С. 10654 - 10665

Опубликована: Ноя. 5, 2021

Bone mesenchymal stem cells (BMSCs) have been used for the treatment of acute uterine injury (AUI)-induced intrauterine adhesion (IUA) via interacting with endothelial progenitor (EPCs), and BMSCs-derived exosomes (BMSCs-exo) may be key regulators this process. However, underlying mechanisms not studied. Based on existed literatures, lipopolysaccharide (LPS) was to induce AUI in mice models EPCs mimic realistic pathogenesis IUA vivo vitro. Our data suggested that LPS induced apoptotic pyroptotic cell death horn tissues EPCs, clinical supported increased levels pro-inflammatory cytokines IL-18 IL-1β were also observed patients' serum samples, silencing NLRP3 rescued viability LPS-treated EPCs. Next, respectively co-cultured BMSCs Transwell system BMSCs-exo, results hinted both BMSCs-exo reversed promoting effects treatment-induced Then, we screened out miR-223-3p, as upstream regulator NLRP3, enriched inactivated NLRP3-mediated pyroptosis delivering miR-223-3p. Interestingly, upregulation miR-223-3p attenuated LPS-induced Collectively, concluded upregulated degrade which further cytotoxic ameliorate AUI.

Язык: Английский

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An Extracellular Vesicle-Cloaked Multifaceted Biocatalyst for Ultrasound-Augmented Tendon Matrix Reconstruction and Immune Microenvironment Regulation

ACS Nano, Год журнала: 2023, Номер 17(17), С. 16501 - 16516

Опубликована: Авг. 24, 2023

The healing of tendon injury is often hindered by peritendinous adhesion and poor regeneration caused the accumulation reactive oxygen species (ROS), development inflammatory responses, deposition type-III collagen. Herein, an extracellular vesicles (EVs)-cloaked enzymatic nanohybrid (ENEV) was constructed to serve as a multifaceted biocatalyst for ultrasound (US)-augmented matrix reconstruction immune microenvironment regulation. ENEV-based exhibits integrated merits treating injury, including efficient catalase-mimetic scavenging ROS in injured tissue, sustainable release Zn2+ ions, cellular uptake augmented US, immunoregulation induced EVs. Our study suggests that ENEVs can promote tenocyte proliferation type-I collagen synthesis at early stage protecting tenocytes from attack. also prompted regulation, polarization macrophages (Mφ) reversed M1φ M2φ. In rat Achilles defect model, combined with US treatment significantly promoted functional recovery reconstruction, restored morphology, suppressed intratendinous scarring, inhibited adhesion. Overall, this offers nanomedicine US-augmented improved outcomes provides alternative strategy design artificial biocatalysts synergetic tissue regenerative therapies.

Язык: Английский

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Mesenchymal Stem Cells and Their Exocytotic Vesicles

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2085 - 2085

Опубликована: Янв. 20, 2023

Mesenchymal stem cells (MSCs), as a kind of pluripotent cells, have attracted much attention in orthopedic diseases, geriatric metabolic and sports functions due to their osteogenic potential, chondrogenic differentiation ability, adipocyte differentiation. Anti-inflammation, anti-fibrosis, angiogenesis promotion, neurogenesis, immune regulation, secreted growth factors, proteases, hormones, cytokines, chemokines MSCs been widely studied liver kidney cardiovascular cerebrovascular diseases. In recent years, many studies shown that the extracellular vesicles similar transplantation all above aspects. Here we review research progress exocrine years.

Язык: Английский

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Stem cell-based therapy for fibrotic diseases: mechanisms and pathways

Stem Cell Research & Therapy, Год журнала: 2024, Номер 15(1)

Опубликована: Июнь 18, 2024

Abstract Fibrosis is a pathological process, that could result in permanent scarring and impairment of the physiological function affected organ; this condition which categorized under term organ failure affect various organs different situations. The involvement major organs, such as lungs, liver, kidney, heart, skin, associated with high rate morbidity mortality across world. Fibrotic disorders encompass broad range complications be traced to illnesses impairments; these from simple skin scars beauty issues severe rheumatologic or inflammatory systemic sclerosis well idiopathic pulmonary fibrosis. Besides, overactivation immune responses during any causing tissue damage contribute pathogenic fibrotic events accompanying healing response; for instance, inflammation resulting engraftment cause formation grafted tissue, even cases where system deals hard clear infections, follow adverse effects. A good example complication post-Covid19 lung fibrosis impair life individuals extensive involvement. However, effective therapies halt slow down progression are missing current clinical settings. Considering immunomodulatory regenerative potential distinct stem cell types, their application an anti-fibrotic agent, capable attenuating has been investigated by many researchers. Although majority studies addressing effects cells indicated potent capabilities, underlying mechanisms, pathways impact processes remain poorly understood. Here, we first, review properties types utilized so far treatments discuss challenges limitations applications settings; then, will summarize general organ-specific mechanisms contributing fibrosis; finally, describe considered employed exerting events.

Язык: Английский

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Injectable Photo-Crosslinked Bioactive BMSCs-BMP2-GelMA Scaffolds for Bone Defect Repair

Frontiers in Bioengineering and Biotechnology, Год журнала: 2022, Номер 10

Опубликована: Март 24, 2022

Injectable hydrogels offer a new therapy option for irregular bone deformities. Based on gelatin methacryloyl (GelMA), marrow mesenchymal stem cells (BMSCs), and morphogenetic protein 2 (BMP2), we created photo-crosslinked composite bioactive scaffold. The scaffolds had appropriate mechanical properties adhesion proliferation, as well good biocompatibility the ability to stimulate BMSCs osteogenic differentiation in vitro. synergistic effect of BMP2 enabled scaffold exhibit higher potential vivo than loaded alone with or BMP2, according imaging histology studies. In conclusion, by promoting BMSCs, based BMSCs-BMP2-GelMA has demonstrated remarkable application regeneration defects repair.

Язык: Английский

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Bone marrow mesenchymal stem cell-derived extracellular vesicles containing miR-181d protect rats against renal fibrosis by inhibiting KLF6 and the NF-κB signaling pathway

Cell Death and Disease, Год журнала: 2022, Номер 13(6)

Опубликована: Июнь 7, 2022

Abstract Recent studies have investigated the ability of extracellular vesicles (EVs) in regulating neighboring cells by transferring signaling molecules, such as microRNAs (miRs) renal fibrosis. EVs released bone marrow mesenchymal stem (BMSCs) contain miR-181d, which may represent a potential therapy for miR-181d has been speculated to regulate Krüppel-like factor 6 (KLF6), activates nuclear factor-kappa B (NF-κB) pathway. Luciferase assays were performed confirm relationship between and KLF6. Gain- loss-of-function vivo vitro assess effect BMSC-derived (BMSC-EVs), contained on KLF6, NF-κB, Transforming growth factor-β (TGF-β)-induced tubular epithelial HK-2 treated with derived from BMSCs followed evaluation collagen type IV α1 (Col4α1), Collagen I α-smooth muscle actin (α-SMA) indicators extent Renal fibrosis was induced rats unilateral ureteral obstruction (UUO) subsequent analysis fibrotic markers. BMSC-EVs had higher expression. Overexpression correlated decrease KLF6 expression well levels IκBα phosphorylation, α-SMA, Col4α1, TGF-βR1 cells. In vivo, treatment miR-181d-containing able restrict progression UUO-induced rats. Together, suppress delivering cells, where it targets inhibits NF-κB

Язык: Английский

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