MSC-EVs alleviate osteoarthritis by regulating microenvironmental cells in the articular cavity and maintaining cartilage matrix homeostasis

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 85, P. 101864 - 101864

Published: Jan. 25, 2023

Language: Английский

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Macrophages—bone marrow mesenchymal stem cells crosstalk in bone healing

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: June 23, 2023

Bone healing is associated with many orthopedic conditions, including fractures and osteonecrosis, arthritis, metabolic bone disease, tumors periprosthetic particle-associated osteolysis. How to effectively promote has become a keen topic for researchers. The role of macrophages marrow mesenchymal stem cells (BMSCs) in gradually come light the development concept osteoimmunity. Their interaction regulates balance between inflammation regeneration, when inflammatory response over-excited, attenuated, or disturbed, it results failure healing. Therefore, an in-depth understanding function regeneration relationship two could provide new directions This paper reviews mechanism significance their interaction. Several therapeutic ideas regulating by targeting crosstalk are also discussed.

Language: Английский

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Revolutionizing osteoarthritis treatment: How mesenchymal stem cells hold the key

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116458 - 116458

Published: March 19, 2024

Osteoarthritis (OA) is a multifaceted disease characterized by imbalances in extracellular matrix metabolism, chondrocyte and synoviocyte senescence, as well inflammatory responses mediated macrophages. Although there have been notable advancements pharmacological surgical interventions, achieving complete remission of OA remains formidable challenge, oftentimes accompanied significant side effects. Mesenchymal stem cells (MSCs) emerged promising avenue for treatment, given their ability to differentiate into chondrocytes facilitate cartilage repair, thereby mitigating the impact an microenvironment induced This comprehensive review aims provide concise overview diverse roles played MSCs treatment OA, while elucidating underlying mechanisms behind these contributions. Specifically, include: (a) Promotion regeneration; (b) Inhibition degradation; (c) Attenuating macrophage-induced microenvironment; (d) Alleviation pain. Understanding paramount developing novel therapeutic strategies. By harnessing regenerative potential immunomodulatory properties MSCs, it may be possible devise more effective safer approaches managing OA. Further research clinical studies are warranted optimize utilization realize full field therapeutics.

Language: Английский

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Immunomodulation Effects of Porcine Cartilage Acellularized Matrix (pCAM) for Osteoarthritis Treatment

Tissue Engineering and Regenerative Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Language: Английский

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Polynucleotides Suppress Inflammation and Stimulate Matrix Synthesis in an In Vitro Cell-Based Osteoarthritis Model

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12282 - 12282

Published: July 31, 2023

Osteoarthritis (OA) is characterized by degeneration of the joint cartilage, inflammation, and a change in chondrocyte phenotype. Inflammation also promotes cell hypertrophy human articular chondrocytes (HC-a) activating NF-κB pathway. Chondrocyte inflammation promote extracellular matrix degradation (ECM). Chondrocytes depend on Smad signaling to control regulate as well maintain ECM. The involvement these two pathways crucial for preserving homeostasis cartilage. In recent years, Polynucleotides Highly Purified Technology (PN-HPT) has emerged promising area research treatment OA. PN-HPT involves use polynucleotide-based agents with controlled natural origins high purification levels. this study, we focused evaluating efficacy specific polynucleotide sodium agent, known CONJURAN, which derived from fish sperm. (PN), are physiologically present function water-soluble nucleic acids gel-like property, have been used treat patients However, mechanisms underlying effect remain unclear. Therefore, investigated PN an OA model HC-a cells were stimulated interleukin-1β (IL-1β) or without treatment. CCK-8 assay was assess cytotoxic effects PN. Furthermore, enzyme-linked immunosorbent utilized detect MMP13 levels, nitric oxide determine inflammation. anti-inflammatory related using quantitative PCR, Western blot analysis, immunofluorescence examine analyze relative markers. inhibited IL-1β induced destruction genes proteins downregulating expression MMP3, MMP13, iNOS, COX-2 while increasing aggrecan (ACAN) collagen II (COL2A1). This study demonstrates, first time, that exerted partially inhibiting pathway Smad2/3 Based our findings, can potentially serve

Language: Английский

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Hyaluronic Acid Viscosupplement Modulates Inflammatory Mediators in Chondrocyte and Macrophage Coculture via MAPK and NF-κB Signaling Pathways

ACS Omega, Journal Year: 2024, Volume and Issue: 9(19), P. 21467 - 21483

Published: May 1, 2024

Osteoarthritis (OA) is a chronic musculoskeletal disorder characterized by cartilage degeneration and synovial inflammation. Paracrine interactions between chondrocytes macrophages play an essential role in the onset progression of OA. In this study, replicating inflammatory response during OA pathogenesis, were treated with interleukin-1β (IL-1β), lipopolysaccharide interferon-γ. addition, coculture system was developed to simulate biological situation joint. we examined impact hyaluronic acid (HA) viscosupplement, particularly Hyruan Plus, on macrophages. Notably, viscosupplement has demonstrated promising outcomes reducing inflammation; however, underlying mechanism action remains elusive. The attenuated inflammation, showing inhibitory effect nitric oxide production, downregulating proinflammatory cytokines such as matrix metalloproteinases (MMP13 MMP3), upregulating expression levels type II collagen aggrecan chondrocytes. HA also reduced level IL-1β, TNF-α, IL-6 macrophages, exerted overall protective partially suppressing MAPK pathway p65/NF-κB signaling Therefore, shows potential for treating arthritic joints.

Language: Английский

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M2 Macrophage-Derived Extracellular Vesicles Encapsulated in Hyaluronic Acid Alleviate Osteoarthritis by Modulating Macrophage Polarization

ACS Biomaterials Science & Engineering, Journal Year: 2024, Volume and Issue: 10(5), P. 3355 - 3377

Published: April 2, 2024

An imbalance between M1 and M2 macrophage polarization is critical in osteoarthritis (OA) development. We investigated the effect of macrophage-derived extracellular vesicles (M2-EVs) to reprogramme macrophages from phenotype for OA treatment. mouse models were treated with M2-EVs. Proteomic analysis was performed evaluate vitro. The as follows: destabilization medial meniscus (DMM) surgery-induced collagenase-induced (CIOA). Hyaluronic acid (HA) used deliver M2-EVs decreased accumulation, repolarized phenotype, mitigated synovitis, reduced cartilage degradation, alleviated subchondral bone damage, improved gait abnormalities CIOA DMM models. Moreover, HA increased retention time enhanced efficiency Furthermore, proteomic demonstrated that exhibited a reprogramming ability similar IL-4, pathways might be NOD-like receptor (NLR), TNF, NF-κB, Toll-like (TLR) signaling pathways. reprogrammed which resulted beneficial effects on attenuation severity. In summary, our study indicated M2-EV-guided promising treatment strategy OA.

Language: Английский

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Interleukin 1β receptor blocker (Anakinra) and regenerative stem cell therapy: two novel approaches effectively ameliorating diabetic cardiomyopathy

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2024, Volume and Issue: 397(10), P. 8023 - 8041

Published: May 22, 2024

Diabetic cardiomyopathy (DCM) is a serious common complication of diabetes. Unfortunately, there no satisfied treatment for those patients and more studies are in critical need to cure them. Therefore, we aimed carry out our current research explore the role two novel therapeutic approaches: one biological drug block inflammatory signaling IL 1beta (IL1β) axis, namely, anakinra; other provision anti-inflammatory regenerative stem cells. Wistar male rats were allocated into four groups: control group: type 2 diabetes mellitus (DM) induced by 6-week high-fat diet (HFD) followed single-dose streptozotocin (STZ) 35 mg/kg i.p., then into: DM: untreated; DM BM-MSCs: received single dose BM-MSCs (1 × 10

Language: Английский

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Adipose-derived mesenchymal stem cells combined with platelet-rich plasma are superior options for the treatment of osteoarthritis

Journal of Orthopaedic Surgery and Research, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 2, 2025

There is currently no definitive treatment for osteoarthritis. We examined the therapeutic effects and underlying mechanisms of platelet-rich plasma (PRP) adipose-derived mesenchymal stem cells (ADSCs), individually or in combination, a rat model anterior cruciate ligament-induced degenerative osteoarthritis (OA) knee. This study seeks to advance clinical approaches OA treatment. Eight- nine-week-old male Sprague-Dawley (SD) rats were randomly assigned two groups: (1) normal control group (Group A) (2) group. The received underwent was further subdivided into six Group B (an injury group), C (high-dose ADSCs), D (PRP combined with high-dose E (low-dose F low-dose G alone). PRP and/or ADSCs administered via intra-articular injection on Days 7, 37, 67 post-surgery. Daily observations recorded activity levels behavior, while weight changes monitored weekly. Digital radiography (DR) conducted 30, 60, 90 post-surgery assess joint surface contour alterations. Histopathological examination inflammatory factor analysis performed cartilage synovial tissue. No abnormal reactions observed any rats, body weights increased as expected (P > 0.05). Significant differences knee swelling rates Wakitani scores between Groups A < 0.01). Knee also differed significantly C–G decreased 60 C–G. TNF-α IL-1β expression higher compared Expression these genes lower than Repeated injections alleviated inflammation pain, promoted tissue repair, modulated immune responses surgically induced OA. combination demonstrated enhanced efficacy, suggesting its potential option

Language: Английский

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The role of natural exosomes from SHED-MSC in immunoregulation of M0/M1 polarized macrophage cells

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 7, 2025

Exosomes (EXOs) as a targeted cell-free therapy could offer new therapeutic strategy for immune-mediated inflammatory diseases, due to their stability and ease of storage handling. This study focused on exosomes derived from stem cells human exfoliated deciduous teeth (SHED-MSC-EXOs) role in managing the balance immunoregulatory macromolecules that play underlying mechanisms THP-1-derived M0/M1 macrophage cells. Flow cytometry confirmed expression CD14, CD68, CD80, CD86 markers these macrophages. Following morphological survival assessments, culture supernatants SHED-MSCs were used isolate exosomes. Once verified, Calcein AM-labeled EXOs introduced The assessed by analyzing surface markers, cytokine production, pro- antioxidant activity. Macrophages treated with exhibited immunomodulatory effects akin those dexamethasone. levels anti-inflammatory including CD206, Arg-1, IL-10, TGF-β, TAC, CAT, SOD, which act immunosuppressive macromolecules, elevated. In contrast, there was reduction pro-inflammatory pro-oxidant CD81, IL-6R, IL-12, TNF-α, MDA, NO, immunostimulatory (P < 0.05). findings suggest SHED-MSC can skew macrophages M2 phenotype inhibit M1 polarization. These nanovesicles, distinct physical properties ability penetrate target cells, may prove beneficial conditions involving depletion macrophage-induced potentially aiding inflammation tissue injury.

Language: Английский

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