Macrophage plasticity: signaling pathways, tissue repair, and regeneration

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: Aug. 1, 2024

Abstract Macrophages are versatile immune cells with remarkable plasticity, enabling them to adapt diverse tissue microenvironments and perform various functions. Traditionally categorized into classically activated (M1) alternatively (M2) phenotypes, recent advances have revealed a spectrum of macrophage activation states that extend beyond this dichotomy. The complex interplay signaling pathways, transcriptional regulators, epigenetic modifications orchestrates polarization, allowing respond stimuli dynamically. Here, we provide comprehensive overview the cascades governing focusing on roles Toll‐like receptors, signal transducer activator transcription proteins, nuclear microRNAs. We also discuss emerging concepts metabolic reprogramming trained immunity, contributing their functional adaptability. Macrophage plasticity plays pivotal role in repair regeneration, macrophages coordinating inflammation, angiogenesis, matrix remodeling restore homeostasis. By harnessing potential novel therapeutic strategies targeting polarization could be developed for diseases, including chronic wounds, fibrotic disorders, inflammatory conditions. Ultimately, deeper understanding molecular mechanisms underpinning will pave way innovative regenerative medicine engineering approaches.

Language: Английский

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Fostering tissue engineering and regenerative medicine to treat musculoskeletal disorders in bone and muscle

Bioactive Materials, Journal Year: 2024, Volume and Issue: 40, P. 345 - 365

Published: June 15, 2024

Language: Английский

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Single-cell analysis of skeletal muscle macrophages reveals age-associated functional subpopulations

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Oct. 19, 2022

Tissue-resident macrophages represent a group of highly responsive innate immune cells that acquire diverse functions by polarizing toward distinct subpopulations. The subpopulations reside in skeletal muscle (SKM) and their changes during aging are poorly characterized. By single-cell transcriptomic analysis with unsupervised clustering, we found 11 macrophage clusters male mouse SKM enriched gene expression programs linked to reparative, proinflammatory, phagocytic, proliferative, senescence-associated functions. Using complementary classification, membrane markers LYVE1 MHCII identified four subgroups: LYVE1−/MHCII hi (M1-like, classically activated), LYVE1+/MHCII lo (M2-like, alternatively two new subgroups, . Notably, one subgroup, , had traits both M2 M1 macrophages, while the other displayed strong phagocytic capacity. Flow cytometric validated presence subgroups LYVE1− were more abundant than LYVE1+ old SKM. A striking increase proinflammatory ( S100a8 S100a9 mRNAs) senescence-related Gpnmb Spp1 was evident from older mice. In sum, have dynamically polarized propose specific contribute senescent

Language: Английский

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Application of mesenchymal stem cell-derived exosomes from different sources in intervertebral disc degeneration

Frontiers in Bioengineering and Biotechnology, Journal Year: 2022, Volume and Issue: 10

Published: Oct. 7, 2022

Intervertebral disc degeneration (IVDD) is a main cause of lower back pain, leading to psychological and economic burdens patients. Physical therapy only delays pain in patients but cannot eliminate the IVDD. Surgery required when patient tolerate or has severe neurological symptoms. Although surgical resection IVD decompression laminae eliminates diseased segment, it damages adjacent normal IVD. There also risk re-protrusion after removal. Cell played crucial role development regenerative medicine. transplantation promotes regeneration degenerative tissue. However, owing lack vascular structure IVD, sufficient nutrients be provided for transplanted mesenchymal stem cells (MSCs). In addition, dead release harmful substances that aggravate Extracellular vesicles (EVs) have been extensively studied as an emerging therapeutic approach. EVs generated by paracrine MSCs retain potential serve carriers deliver their contents target regulate cell activity. Owing double-layered membrane structure, low immunogenicity no immune rejection. Therefore, are considered modality they limited mass production loading rates. this review, advantages introduced, application MSC-EVs IVDD discussed. The current limitations future applications described.

Language: Английский

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Research progress on macrophage polarization during osteoarthritis disease progression: a review

Journal of Orthopaedic Surgery and Research, Journal Year: 2024, Volume and Issue: 19(1)

Published: Sept. 28, 2024

Language: Английский

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Nano-biomaterials and advanced fabrication techniques for engineering skeletal muscle tissue constructs in regenerative medicine

Nano Convergence, Journal Year: 2023, Volume and Issue: 10(1)

Published: Oct. 21, 2023

Abstract Engineered three-dimensional (3D) tissue constructs have emerged as a promising solution for regenerating damaged muscle resulting from traumatic or surgical events. 3D architecture and function of the can be customized by selecting types biomaterials cells that engineered with desired shapes sizes through various nano- micro-fabrication techniques. Despite significant progress in this field, further research is needed to improve, terms properties fabrication techniques, resemblance complex native tissues, potentially enhancing regeneration restoring function. In review, we discuss latest trends using nano-biomaterials advanced nano-/micro-fabrication techniques creating their ability. Current challenges potential solutions are highlighted, implications opportunities future perspective including possibility personalized biomanufacturable platforms.

Language: Английский

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SP1 transcriptionally activates HTR2B to aggravate traumatic spinal cord injury by shifting microglial M1/M2 polarization

Journal of Orthopaedic Surgery and Research, Journal Year: 2024, Volume and Issue: 19(1)

Published: April 8, 2024

Abstract Background Spinal cord injury (SCI) can result in structural and functional damage to the spinal cord, which may lead loss of limb movement sensation, bowel bladder control, other complications. Previous studies have revealed critical influence trans-acting transcription factor 1 (SP1) neurological pathologies, however, its role mechanism SCI not been fully studied. Methods The study was performed using mouse microglia BV2 stimulated lipopolysaccharide (LPS) male adult mice subjected hitting. Western blotting detect protein expression SP1, 5-hydroxytryptamine (serotonin) receptor 2B (HTR2B), BCL2-associated x (Bax), B-cell lymphoma-2 (Bcl-2), inducible nitric oxide synthase (iNOS), clusters differentiation 86 (CD86), Arginase (Arg-1) 206 (CD206). Cell viability apoptosis were analyzed by MTT assay TUNEL assay. mRNA levels tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-4 (IL-4) factor-β (TNF-β) quantified quantitative real-time polymerase chain reaction. association SP1 HTR2B identified chromatin immunoprecipitation dual-luciferase reporter HE staining analyze pathological conditions tissues. Results LPS treatment induced cell inhibited polarization from M1 M2 phenotype, accompanied an increase Bax a decrease Bcl-2 expression, these effects relieved after silencing. Mechanism assays that transcriptionally activated cells, knockdown rescued LPS-induced on microglial M1/M2 polarization. Moreover, absence promoted phenotype decreasing expression. model further showed downregulation could attenuate hitting-induced promoting tissues Conclusion aggravate traumatic shifting

Language: Английский

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Boosting the peripheral immune response in the skeletal muscles improved motor function in ALS transgenic mice

Molecular Therapy, Journal Year: 2022, Volume and Issue: 30(8), P. 2760 - 2784

Published: April 27, 2022

Monocyte chemoattractant protein-1 (MCP1) is one of the most powerful pro-inflammatory chemokines. However, its signaling pivotal in driving injured axon and muscle regeneration. We previously reported that MCP1 more strongly upregulated nervous system slow-progressing than fast-progressing SOD1G93A mice, latter showing a poor immune response eventual massive nerve degeneration. To assess MCP1-mediated therapeutic role, we boosted chemokine along motor unit two models through single intramuscular injection scAAV9 vector engineered with Mcp1 gene. provided direct evidence underlying role skeletal regeneration thus speed ALS progression. The comparative study performed fast- mice spotlights nature temporal activation inflammatory as limiting factors to preserve periphery interfere disease course. In addition, recorded novel pleiotropic promoting peripheral modulating neuroinflammation, ultimately preventing neurodegeneration. Altogether, these observations highlight key determinant for variability proffer reasonable explanation failure systemic immunomodulatory treatments, suggesting new potential strategies hamper

Language: Английский

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Exosomal miR-122 derived from M2 macrophages induces osteogenic differentiation of bone marrow mesenchymal stem cells in the treatment of alcoholic osteonecrosis of the femoral head

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

Published: Jan. 29, 2025

Alcoholic osteonecrosis of the femoral head (AIONFH) is caused by long-term heavy drinking, which leads to abnormal alcohol and lipid metabolism, resulting in tissue damage, then pathological necrosis tissue. If not treated time clinical practice, it will seriously affect quality life patients even require hip replacement treat alcoholic necrosis. This study confirm whether M2 macrophage exosome (M2-Exo) miR-122 mediates alcohol-induced BMSCs osteogenic differentiation, ultimately leading inhibition macrophages were identified flow cytometry, isolated exosomes characterized transmission electron microscopy (TEM) Nanoparticle Tracking Analysis (NTA). Next, was overexpressed transfecting mimic, expression their evaluated. Subsequently, effect exosomal on differentiation ability detected, including cell proliferation, osteogenic-related genes (RUNX2, BMP2, OPN, ALP), calcium nodule formation. Finally, therapeutic M2-Exo analyzed a rat model AIONFH, bone repair damage evaluated Micro-CT, RT-qPCR, HE, Masson staining, immunohistochemistry (COL I). The results showed that successfully polarized, with an average particle size 156.4 nm concentration 3.2E + 12 particles/mL. significantly higher than M0 macrophages, mimic can increase content M2-Exo. promote marrow BMSCs, enhance viability, osteogenesis-related genes. After being applied AIONFH model, injection M2-exo mimics improved articular cartilage, alleviated changes, promoted regeneration M2-macrophage-derived induces mesenchymal stem cells treating AIONFH.

Language: Английский

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Development of a macrophage polarization-modulating therapeutic agent for osteoarthritis treatment

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

Published: March 14, 2025

Osteoarthritis (OA) is a common chronic degenerative joint disease. Recent studies have emphasized the crucial role of macrophages, particularly tissue-resident macrophages (Tissue-Resident Macrophages, TRMs), in pathogenesis and progression OA. Under physiological conditions, TRMs maintain homeostasis, but under various stimuli, they can polarize into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. An imbalance macrophage polarization, favoring phenotype, leads to sustained inflammation, cartilage degradation, osteophyte formation, further exacerbating OA symptoms structural damage. This article reviews current understanding polarization OA, with particular emphasis on mechanisms by which influence microenvironment. It explores therapeutic potential drug molecular platforms aimed at regulating shifting balance from M2. The discussion includes pharmacological agents such as corticosteroids, hyaluronic acid derivatives, monoclonal antibodies, bioactive molecules like Squid Type II Collagen (SCII) modulating function slowing progression. Additionally, examines advancements gene therapy methods targeting utilizing nanotechnology-based delivery systems enhance specificity efficiency phenotype regulation. Targeting through sophisticated presents promising strategy for developing novel diagnostic interventions osteoarthritis.

Language: Английский

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