Extracellular vesicle-guided in situ reprogramming of synovial macrophages for the treatment of rheumatoid arthritis

Kim, Hyo‐Suk; Back, Ji Hyun; Han, Geonhee; Lee, Su Jin; Park, Yae Eun; Gu, Man Bock; Yang, Yoosoo; Lee, Ji Eun; Kim, Sun Hwa

doi:10.1016/j.biomaterials.2022.121578

Cited by 31 publications

(23 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…N/A M2 macrophage-derived EVs reprogrammed M1 macrophages within joints to quiescent, antiinflammatory M2 state leading to reduced inflammation. [185] DLS, dynamic light scattering; FACS, fluorescence activated cell sorting (flow cytometry); nanoFCM, nano-flow cytometry; NTA, nanoparticle tracking analysis; PET/CT, positron emission tomography/computed tomography; SEM, scanning electron microscopy; SLE, systemic lupus erythematosus; TEM, transmission electron microscopy; WB, western blotting.…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

Extracellular vesicles arising from apoptosis: forms, functions, and applications

Gregory

Rimmer

2023

The Journal of Pathology

View full text Add to dashboard Cite

Extracellular vesicles (EVs) are lipid bilayer‐enclosed subcellular bodies produced by most, if not all cells. Research over the last two decades has recognised the importance of EVs in intercellular communication and horizontal transfer of biological material. EVs range in diameter from tens of nanometres up to several micrometres and are able to transfer a spectrum of biologically active cargoes – from whole organelles, through macromolecules including nucleic acids and proteins, to metabolites and small molecules – from their cells of origin to recipient cells, which may consequently become physiologically or pathologically altered. Based on their modes of biogenesis, the most renowned EV classes are (1) microvesicles, (2) exosomes (both produced by healthy cells), and (3) EVs from cells undergoing regulated death by apoptosis (ApoEVs). Microvesicles bud directly from the plasma membrane, while exosomes are derived from endosomal compartments. Current knowledge of the formation and functional properties of ApoEVs lags behind that of microvesicles and exosomes, but burgeoning evidence indicates that ApoEVs carry manifold cargoes, including mitochondria, ribosomes, DNA, RNAs, and proteins, and perform diverse functions in health and disease. Here we review this evidence, which demonstrates substantial diversity in the luminal and surface membrane cargoes of ApoEVs, permitted by their very broad size range (from around 50 nm to >5 μm; the larger often termed apoptotic bodies), strongly suggests their origins through both microvesicle‐ and exosome‐like biogenesis pathways, and indicates routes through which they interact with recipient cells. We discuss the capacity of ApoEVs to recycle cargoes and modulate inflammatory, immunological, and cell fate programmes in normal physiology and in pathological scenarios such as cancer and atherosclerosis. Finally, we provide a perspective on clinical applications of ApoEVs in diagnostics and therapeutics. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

show abstract

Section: Rheumatoid Arthritismentioning

confidence: 99%

Extracellular vesicles arising from apoptosis: forms, functions, and applications

Gregory

Rimmer

2023

The Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…Notably, another study demonstrated the remarkable in situ macrophage-repolarizing capacity of M2-EVs, in which synovial macrophages switched from the M1 to M2 phenotype in a collagen-induced rheumatoid arthritis (RA) mouse model. 17 However, whether M2-EVs exert therapeutic effects in OA is not clear. Therefore, investigating the role of M2-EVs in macrophage reprogramming during OA progression and exploring their potential applications may lead to new therapeutic strategies for OA treatment.…”

Section: Introductionmentioning

confidence: 99%

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

Yuan,

Yang,

Zheng

et al. 2024

ACS Biomater. Sci. Eng.

View full text Add to dashboard Cite

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

show abstract

“…Adaptive immune cells referring to B cells and T cells, are mainly responsible for mediating humoral immunity and cellular immunity, respectively ( 1 ). However, the chaotic responses of immune cells often lead to various inflammatory diseases like chronic wounds ( 2 ), rheumatoid arthritis ( 3 ), inflammatory bowel diseases ( 4 ), encephalomyelitis ( 5 ), and so on, imposing a heavy burden on the economy and society ( 6 , 7 ). For example, the unbalanced ratio of anti-inflammatory M2 macrophages (M2φ)/pro-inflammatory M1 macrophages (M1φ) or delayed transition from M1φ to M2φ phenotype of macrophages leads to excessive inflammation, impairing healing process of chronic wounds ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory potential of mesenchymal stem cell-derived extracellular vesicles: Targeting immune cells

Liu

Wei

Lu³

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

Various intractable inflammatory diseases caused by disorders of immune systems have pressed heavily on public health. Innate and adaptive immune cells as well as secreted cytokines and chemokines are commanders to mediate our immune systems. Therefore, restoring normal immunomodulatory responses of immune cells is crucial for the treatment of inflammatory diseases. Mesenchymal stem cell derived extracellular vesicles (MSC-EVs) are nano-sized double-membraned vesicles acting as paracrine effectors of MSCs. MSC-EVs, containing a variety of therapeutic agents, have shown great potential in immune modulation. Herein, we discuss the novel regulatory functions of MSC-EVs from different sources in the activities of innate and adaptive immune cells like macrophages, granulocytes, mast cells, natural killer (NK) cells, dendritic cells (DCs) and lymphocytes. Then, we summarize the latest clinical trials of MSC-EVs in inflammatory diseases. Furthermore, we prospect the research trend of MSC-EVs in the field of immune modulation. Despite the fact that the research on the role of MSC-EVs in regulating immune cells is in infancy, this cell-free therapy based on MSC-EVs still offers a promising solution for the treatment of inflammatory diseases.

show abstract

Extracellular vesicle-guided in situ reprogramming of synovial macrophages for the treatment of rheumatoid arthritis

Cited by 31 publications

References 58 publications

Extracellular vesicles arising from apoptosis: forms, functions, and applications

Extracellular vesicles arising from apoptosis: forms, functions, and applications

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

Immunomodulatory potential of mesenchymal stem cell-derived extracellular vesicles: Targeting immune cells

Contact Info

Product

Resources

About