The role of macrophage subtypes and exosomes in immunomodulation

Gharavi, Abdulwahab Teflischi; Hanjani, Niloofar Asadi; Movahed, Elaheh; Doroudian, Mohammad

doi:10.1186/s11658-022-00384-y

Cited by 100 publications

(46 citation statements)

References 143 publications

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“…They have been considered in recent years as ideal vesicles for future biologic therapies and have demonstrated their role and potential in the repair of damage in a variety of organ systems [23,[45][46][47]. Exosomes are EVs with a size range of 40-160 nm (average ~ 100 nm) in diameter and exert their regulatory effects mainly through their inclusions, such as proteins, miRNAs, and long noncoding RNAs [48][49][50]. Of these, miRNAs are currently considered the most diverse.…”

Section: Discussionmentioning

confidence: 99%

Human umbilical cord mesenchymal stem cell exosome-derived miR-874-3p targeting RIPK1/PGAM5 attenuates kidney tubular epithelial cell damage

Chen

Guo

et al. 2023

Cell Mol Biol Lett

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Background Kidney insults due to various pathogenic factors, such as trauma, infection, and inflammation, can cause tubular epithelial cell injury and death, leading to acute kidney injury and the transformation of acute kidney injury to chronic kidney disease. There is no definitive treatment available. In previous studies, human umbilical cord mesenchymal stem cells have been shown to promote kidney injury. In this preclinical study, we investigate the role and mechanism of human umbilical cord mesenchymal stem cell exosomes (HucMSC-Exos) on the repair of renal tubular epithelial cells after injury. Methods C57BL/6 mice underwent unilateral ureteral obstruction, and epithelial cell injury was induced in HK-2 cells by cisplatin. HucMSC-Exos were assessed in vivo and in vitro. The extent of renal cell injury, activation of necroptosis pathway, and mitochondrial quality-control-related factors were determined in different groups. We also analyzed the possible regulatory effector molecules in HucMSC-Exos by transcriptomics. Results HucMSC-Exo inhibited necroptosis after renal tubular epithelial cell injury and promoted the dephosphorylation of the S637 site of the Drp1 gene by reducing the expression of PGAM5. This subsequently inhibited mitochondrial fission and maintained mitochondrial functional homeostasis, mitigating renal injury and promoting repair. In addition, HucMSC-Exo displayed a regulatory role by targeting RIPK1 through miR-874-3p. Conclusion The collective findings of the present study demonstrate that HucMSC-Exos can regulate necroptosis through miR-874-3p to attenuate renal tubular epithelial cell injury and enhance repair, providing new therapeutic modalities and ideas for the treatment of AKI and the process of AKI to CKD transformation to mitigate renal damage.

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Section: Discussionmentioning

confidence: 99%

Human umbilical cord mesenchymal stem cell exosome-derived miR-874-3p targeting RIPK1/PGAM5 attenuates kidney tubular epithelial cell damage

Chen

Guo

et al. 2023

Cell Mol Biol Lett

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“…Additionally, they can merge with the plasma membranes of target cells [ 41 , 42 ]. MSCs are multipotent, ubiquitous cells that can differentiate into various mesodermal germ layer cell types [ 13 , 40 , 43 , 44 , 45 ]. MSCs have two fundamental properties: (i) they are immunomodulatory; hence, they can decrease the levels of cytokines such as interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) while boosting the levels of transforming growth factor beta (TGF-β); and (ii) they have a strong regeneration capacity [ 26 ].…”

Section: Mesenchymal Stem Cell-derived Exosomesmentioning

confidence: 99%

“…For instance, macrophages and reticuloendothelial cells can directly or indirectly eliminate liposomes. Moreover, multiple investigations have demonstrated that exosomes avoid the immune system and prolong circulation time [ 11 , 12 , 13 ]. Nucleic acids (DNA, ribonucleic acid, micro-RNAs, and long noncoding RNAs (lncRNAs)), lipids, metabolites, proteins, cytosolic proteins, glycoconjugates, amino acids, and membrane proteins are embedded in exosomes ( Figure 1 A).…”

Section: Introductionmentioning

confidence: 99%

Exosomes as Rheumatoid Arthritis Diagnostic Biomarkers and Therapeutic Agents

et al. 2023

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Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder that causes systemic inflammation, autoimmunity, and joint abnormalities that result in permanent disability. Exosomes are nanosized extracellular particles found in mammals (40–100 nm). They are a transporter of lipids, proteins, and genetic material involved in mammalian cell–cell signaling, biological processes, and cell signaling. Exosomes have been identified as playing a role in rheumatoid arthritis-related joint inflammation (RA). Uniquely functioning extracellular vesicles (EVs) are responsible for the transport of autoantigens and mediators between distant cells. In addition, paracrine factors, such as exosomes, modulate the immunomodulatory function of mesenchymal stem cells (MSCs). In addition to transporting genetic information, exosomes convey miRNAs between cells and have been studied as drug delivery vehicles. In animal models, it has been observed that MSCs secrete EVs with immunomodulatory properties, and promising results have been observed in this area. By understanding the diversity of exosomal contents and their corresponding targets, it may be possible to diagnose autoimmune diseases. Exosomes can be employed as diagnostic biomarkers for immunological disorders. We here discuss the most recent findings regarding the diagnostic, prognostic, and therapeutic potential of these nanoparticles in rheumatoid arthritis and provide an overview of the evidence pertaining to the biology of exosomes in RA.

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“…The approaches that change the balance of macrophage phenotypes seem effective through dynamic regulation of immune systems [ 85 , 86 ]. As shown above, exosomes are a useful tool to regulate macrophage polarization in tumor cells, and then in current years, anticancer effects through the regulation of macrophage polarization by exosomes have been investigated [ 104 ] ( Table 2 ). Cervical cancer is the fourth most common cancer among women worldwide and is difficult to diagnose in the early stage, where miR-423-3p was suggested as a potential modulator of the cancer progression.…”

Section: Exosome-induced Macrophage Polarization In Cancersmentioning

confidence: 99%

The Potential Use of Exosomes in Anti-Cancer Effect Induced by Polarized Macrophages

et al. 2023

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The rapid development of aberrant cells outgrowing their normal bounds, which can subsequently infect other body parts and spread to other organs—a process known as metastasis—is one of the significant characteristics of cancer. The main reason why cancer patients die is because of widespread metastases. This abnormal cell proliferation varies in cancers of over a hundred types, and their response to treatment can vary substantially. Several anti-cancer drugs have been discovered to treat various tumors, yet they still have harmful side-effects. Finding novel, highly efficient targeted therapies based on modifications in the molecular biology of tumor cells is essential to reduce the indiscriminate destruction of healthy cells. Exosomes, an extracellular vesicle, are promising as a drug carrier for cancer therapy due to their good tolerance in the body. In addition, the tumor microenvironment is a potential target to regulate in cancer treatment. Therefore, macrophages are polarized toward M1 and M2 phenotypes, which are involved in cancer proliferation and are malignant. It is evident from recent studies that controlled macrophage polarization might contribute to cancer treatment, by the direct way of using miRNA. This review provides an insight into the potential use of exosomes to develop an ‘indirect’, more natural, and harmless cancer treatment through regulating macrophage polarization.

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The role of macrophage subtypes and exosomes in immunomodulation

Cited by 100 publications

References 143 publications

Human umbilical cord mesenchymal stem cell exosome-derived miR-874-3p targeting RIPK1/PGAM5 attenuates kidney tubular epithelial cell damage

Human umbilical cord mesenchymal stem cell exosome-derived miR-874-3p targeting RIPK1/PGAM5 attenuates kidney tubular epithelial cell damage

Exosomes as Rheumatoid Arthritis Diagnostic Biomarkers and Therapeutic Agents

The Potential Use of Exosomes in Anti-Cancer Effect Induced by Polarized Macrophages

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