Mesenchymal stromal cell-based therapy for cartilage regeneration in knee osteoarthritis

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

Опубликована: Янв. 10, 2022

Osteoarthritis, as a degenerative disease, is common problem and results in high socioeconomic costs rates of disability. The most commonly affected joint the knee characterized by progressive destruction articular cartilage, loss extracellular matrix, inflammation. Mesenchymal stromal cell (MSC)-based therapy has been explored new regenerative treatment for osteoarthritis recent years. However, detailed functions MSC-based related mechanism, especially cartilage regeneration, have not explained. Hence, this review summarized how to choose, authenticate, culture different origins MSCs derived exosomes. Moreover, clinical application latest mechanistical findings regeneration were also demonstrated.

Язык: Английский

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Engineering exosomes and biomaterial-assisted exosomes as therapeutic carriers for bone regeneration

Stem Cell Research & Therapy, Год журнала: 2023, Номер 14(1)

Опубликована: Март 29, 2023

Abstract Mesenchymal stem cell-based therapy has become an effective therapeutic approach for bone regeneration. However, there are still limitations in successful clinical translation. Recently, the secretome of mesenchymal cells, especially exosome, plays a critical role promoting repair and Exosomes nanosized, lipid bilayer-enclosed structures carrying proteins, lipids, RNAs, metabolites, growth factors, cytokines have attracted great attention their potential application regenerative medicine. In addition, preconditioning parental cells exosome engineering can enhance exosomes treating defects. Moreover, with recent advancements various biomaterials to functions exosomes, biomaterial-assisted promising strategy This review discusses different insights regarding roles regeneration summarizes applications as safe versatile agent delivery platforms. The current hurdles transitioning from bench bedside also discussed.

Язык: Английский

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Understanding exosomes: Part 2—Emerging leaders in regenerative medicine

Periodontology 2000, Год журнала: 2024, Номер 94(1), С. 257 - 414

Опубликована: Фев. 1, 2024

Abstract Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with ability to communicate other tissues and cell types over long distances. Their use in regenerative medicine has gained tremendous momentum recently due their be utilized as therapeutic options for a wide array diseases/conditions. Over 5000 publications currently being published yearly on this topic, number is only expected dramatically increase novel strategies continue developed. Today exosomes have been applied numerous contexts including neurodegenerative disorders (Alzheimer's disease, central nervous system, depression, multiple sclerosis, Parkinson's post‐traumatic stress disorders, traumatic brain injury, peripheral nerve injury), damaged organs (heart, kidney, liver, stroke, myocardial infarctions, ovaries), degenerative processes (atherosclerosis, diabetes, hematology musculoskeletal degeneration, osteoradionecrosis, respiratory disease), infectious diseases (COVID‐19, hepatitis), procedures (antiaging, bone regeneration, cartilage/joint osteoarthritis, cutaneous wounds, dental dermatology/skin erectile dysfunction, hair regrowth, intervertebral disc repair, spinal cord vascular regeneration), cancer therapy (breast, colorectal, gastric osteosarcomas), immune function (allergy, autoimmune regulation, inflammatory diseases, lupus, rheumatoid arthritis). This scoping review first its kind aimed at summarizing extensive potential broad range disorders.

Язык: Английский

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Exploring interactions between extracellular vesicles and cells for innovative drug delivery system design

Advanced Drug Delivery Reviews, Год журнала: 2021, Номер 173, С. 252 - 278

Опубликована: Март 31, 2021

Extracellular vesicles (EVs) are submicron cell-secreted structures containing proteins, nucleic acids and lipids. EVs can functionally transfer these cargoes from one cell to another modulate physiological pathological processes. Due their presumed biocompatibility capacity circumvent canonical delivery barriers encountered by synthetic drug systems, have attracted considerable interest as vehicles. However, it is unclear which mechanisms molecules orchestrate EV-mediated cargo recipient cells. Here, we review how EV properties been exploited improve the efficacy of small molecule drugs. Furthermore, explore surface could be directly or indirectly involved in cells discuss cellular reporter systems with such studied. Finally, elaborate on currently identified processes delivery. Through topics, provide insights critical effectors EV-cell interface may nature-inspired strategies.

Язык: Английский

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Curcumin-primed human BMSC-derived extracellular vesicles reverse IL-1β-induced catabolic responses of OA chondrocytes by upregulating miR-126-3p

Stem Cell Research & Therapy, Год журнала: 2021, Номер 12(1)

Опубликована: Апрель 29, 2021

Curcumin has anti-inflammatory effects and qualifies as a potential candidate for the treatment of osteoarthritis (OA). However, curcumin limited bioavailability. Extracellular vesicles (EVs) are released by multiple cell types act molecule carrier during intercellular communication. We assume that EVs can maintain bioavailability stability after encapsulation. Here, we evaluated modulatory curcumin-primed human (h)BMSC-derived (Cur-EVs) on IL-1β stimulated osteoarthritic chondrocytes (OA-CH).CellTiter-Blue Viability- (CTB), Caspase 3/7-, live/dead assays were used to determine range cytotoxic concentrations hBMSC OA-CH. Cur-EVs control harvested from culture supernatants ultracentrifugation. Western blotting (WB), transmission electron microscopy, nanoparticle tracking analysis performed characterize EVs. The intracellular incorporation derived PHK26 labeled or was tested adding OA-CH cultures. pre-stimulated with IL-1β, followed Cur-EV EV 24 h subsequent viability, apoptosis, migration (scratch assay). Relative expression selected anabolic catabolic genes assessed qRT-PCR. Furthermore, WB evaluate phosphorylation Erk1/2, PI3K/Akt, p38MAPK in effect hsa-miR-126-3p IL-1β-induced determined using CTB-, assays, WB.Cur-EVs promoted viability reduced apoptosis IL-1β-stimulated attenuated inhibition migration. increased gene BCL2, ACAN, SOX9, COL2A1 decreased IL1B, IL6, MMP13, COL10A1 In addition, p38 MAPK, induced is prevented Cur-EVs. IL-1β-reduced mimic reversed IL-1β.Cur-EVs alleviated promoting migration, reducing MAPK thereby modulating pro-inflammatory signaling pathways. Treatment upregulation which involved modulation response may be considered promising drug delivery vehicles helping alleviate OA.

Язык: Английский

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Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis

Journal of Nanobiotechnology, Год журнала: 2021, Номер 19(1)

Опубликована: Июнь 30, 2021

Abstract Background Extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) may play a vital role in variety of biological processes, including cartilage regeneration. However, few studies reported their potential the development osteoarthritis (OA) previously. In this study, we explored roles and underlying mechanism MSCs-EVs OA. Results Co-culture experiments revealed that could promote expression collagen type II alpha 1 chain (COL2A1), SRY-box transcription factor 9 (SOX9) Aggrecan while negatively regulate chondrocyte hypertrophy markers matrix metallopeptidase 13 (MMP-13) RUNX family 2 (Runx2) mouse chondrocytes OA model. Besides, results cell indicated notably weaken suppression proliferation, migration promotion apoptosis via interleukin1β (IL-1β) induction. addition, MSCs-circHIPK3-EVs (EVs derived from MSCs overexpressing circHIPK3) considerably improved IL-1β-induced injury. Mechanistically, elucidated circHIPK3 directly bind to miR-124-3p subsequently elevate target gene MYH9. Conclusion The findings our study demonstrated EVs-circHIPK3 participated MSCs-EVs-mediated proliferation induction inhibition miR-124-3p/MYH9 axis. This offers promising novel cell-free therapy for treating Graphic abstract

Язык: Английский

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An update on the role of miR-124 in the pathogenesis of human disorders

Biomedicine & Pharmacotherapy, Год журнала: 2021, Номер 135, С. 111198 - 111198

Опубликована: Янв. 8, 2021

MicroRNA-124 (miR-124) is a copious miRNA in the brain, but it expressed wide range of human/animal tissues participating pathogenesis several disorders. Based on its important function development nervous system, abnormal expression miR-124 has been detected system diseases including Alzheimer's disease, Parkinson's Hypoxic-Ischemic Encephalopathy, Huntington's and ischemic stroke. In addition to these conditions, contributes cardiovascular disorders, hypertension, atherosclerosis. Besides, shown be down-regulated human cancers such as colorectal cancer, breast gastric glioma, pancreatic other types cancer. Yet, few studies have reported upregulation some cancer types. current study, we describe role malignant non-malignant conditions.

Язык: Английский

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Therapeutic potential of exosome‐based personalized delivery platform in chronic inflammatory diseases

Asian Journal of Pharmaceutical Sciences, Год журнала: 2022, Номер 18(1), С. 100772 - 100772

Опубликована: Дек. 31, 2022

In the inflammatory microenvironment, there are numerous exosomes secreted by immune cells (Macrophages, neutrophils, dendritic cells), mesenchymal stem (MSCs) and platelets as intercellular communicators, which participate in regulation of inflammation modulating gene expression releasing anti-inflammatory factors. Due to their good biocompatibility, accurate targeting, low toxicity immunogenicity, these able selectively deliver therapeutic drugs site through interactions between surface-antibody or modified ligand with cell surface receptors. Therefore, role exosome-based biomimetic delivery strategies diseases has attracted increasing attention. Here we review current knowledge techniques for exosome identification, isolation, modification drug loading. More importantly, highlight progress using treat chronic such rheumatoid arthritis (RA), osteoarthritis (OA), atherosclerosis (AS), bowel disease (IBD). Finally, also discuss potential challenges carriers.

Язык: Английский

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Pharmacological Mechanisms and Clinical Applications of Curcumin: Update

Aging and Disease, Год журнала: 2022, Номер 14(3), С. 716 - 716

Опубликована: Ноя. 17, 2022

Curcumin, a well-known hydrophobic polyphenol extracted from the rhizomes of turmeric (Curcuma longa L.), has attracted great interest in last ten years due to its multiple pharmacological activities. A growing body evidence manifested that curcumin extensive activities including anti-inflammatory, anti-oxygenation, lipid regulation, antiviral, and anticancer with hypotoxicity minor adverse reactions. However, disadvantages low bioavailability, short half-life plasma, drug concentration blood, poor oral absorption severely limited clinical application curcumin. Pharmaceutical researchers have carried out plenty dosage form transformations improve druggability achieved remarkable results. Therefore, objective this review summarizes research progress, problems improvement methods curcumin's druggability. By reviewing latest progress curcumin, we believe broad prospect for wide range few side effects. The deficiencies lower bioavailability could be improved by transformation. still requires further study regarding underlying mechanism trial verification.

Язык: Английский

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Engineering of MSC-Derived Exosomes: A Promising Cell-Free Therapy for Osteoarthritis

Membranes, Год журнала: 2022, Номер 12(8), С. 739 - 739

Опубликована: Июль 28, 2022

Osteoarthritis (OA) is characterized by progressive cartilage degeneration with increasing prevalence and unsatisfactory treatment efficacy. Exosomes derived from mesenchymal stem cells play an important role in alleviating OA promoting regeneration, inhibiting synovial inflammation mediating subchondral bone remodeling without the risk of immune rejection tumorigenesis. However, low yield, weak activity, inefficient targeting ability unpredictable side effects natural exosomes have limited their clinical application. At present, various approaches been applied exosome engineering to regulate production function, such as pretreatment parental cells, drug loading, genetic surface modification. Biomaterials also proved facilitate efficient delivery enhance effectiveness. Here, we summarize current understanding biogenesis, isolation characterization exosomes, focus on large-scale preparation engineered well therapeutic potential OA, thus providing novel insights into exploring advanced MSC-derived exosome-based cell-free therapy for OA.

Язык: Английский

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