Small Extracellular Vesicles in Transplant Rejection

Gołębiewska, Justyna; Wardowska, Anna; Pietrowska, Monika; Wojakowska, Anna; Dębska-Ślizień, Alicja

doi:10.3390/cells10112989

Cited by 20 publications

(18 citation statements)

References 182 publications

(247 reference statements)

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“…For example, apoptotic exosome-like vesicles can induce autoantibodies to the basement membrane heparan sulfate proteoglycan perlecan (also known as HSPG2) in naive mice; these antibodies are known to be involved in graft rejection and, indeed, increased perlecan-specific antibody production results in allograft inflammation in mice transplanted with MHC-mismatched aortic grafts 103 . Importantly, profiling of circulating EVs may predict transplant rejection 104 . Indeed, the number of donor-derived exosomes in peripheral blood samples could indicate early rejection with high specificity and sensitivity in a mouse model of heterotopic heart transplantation 105 .…”

Section: Autoimmunity and Transplantationmentioning

confidence: 99%

“… In patients with COVID-19, increased levels of circulating extracellular vesicles (EVs) that carry the SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2) are detected, and the EV-associated coatomer complex subunit β2 (COPB2) predicts COVID-19 severity 153 . EV-associated molecular signatures are proposed as candidate biomarkers in lung, heart, kidney and liver transplantation, and pancreatic island transplant rejection as reviewed recently 104 . In human sepsis, levels of elongated neutrophil-derived structures are highly increased in the blood plasma 85 .…”

Section: Therapeutic Potentialmentioning

confidence: 99%

“…EV-associated molecular signatures are proposed as candidate biomarkers in lung, heart, kidney and liver transplantation, and pancreatic island transplant rejection as reviewed recently 104 .…”

Section: Therapeutic Potentialmentioning

confidence: 99%

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The roles of extracellular vesicles in the immune system

2022

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The twenty-first century has witnessed major developments in the field of extracellular vesicle (EV) research, including significant steps towards defining standard criteria for the separation and detection of EVs. The recent recognition that EVs have the potential to function as biomarkers or as therapeutic tools has attracted even greater attention to their study. With this progress in mind, an updated comprehensive overview of the roles of EVs in the immune system is timely. This Review summarizes the roles of EVs in basic processes of innate and adaptive immunity, including inflammation, antigen presentation, and the development and activation of B cells and T cells. It also highlights key progress related to deciphering the roles of EVs in antimicrobial defence and in allergic, autoimmune and antitumour immune responses. It ends with a focus on the relevance of EVs to immunotherapy and vaccination, drawing attention to ongoing or recently completed clinical trials that aim to harness the therapeutic potential of EVs.

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Section: Autoimmunity and Transplantationmentioning

confidence: 99%

Section: Therapeutic Potentialmentioning

confidence: 99%

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The roles of extracellular vesicles in the immune system

2022

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“…EVs have emerged as informative biomarkers with the potential to become a valuable tool for the diagnosis and treatment monitoring of various diseases. EVs can be used as biological indicators for cardiometabolic diseases [ 66 , 67 , 68 , 69 ], neurological diseases [ 70 , 71 , 72 , 73 ], liver diseases [ 74 , 75 ], kidney diseases [ 76 ], respiratory diseases [ 77 ], skin diseases [ 2 , 78 ], and detection of graft rejection [ 79 ]. Small EVs from oral biofluids (i.e., saliva and gingival crevicular fluid) may act as biomarkers for diagnosing oral diseases noninvasively [ 80 , 81 ].…”

Section: Therapeutic Value Of Extracellular Vesiclesmentioning

confidence: 99%

Scalable Production of Extracellular Vesicles and Its Therapeutic Values: A Review

Kee

Al-Masawa

et al. 2022

IJMS

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Extracellular vesicles (EVs) are minute vesicles with lipid bilayer membranes. EVs are secreted by cells for intercellular communication. Recently, EVs have received much attention, as they are rich in biological components such as nucleic acids, lipids, and proteins that play essential roles in tissue regeneration and disease modification. In addition, EVs can be developed as vaccines against cancer and infectious diseases, as the vesicle membrane has an abundance of antigenic determinants and virulent factors. EVs for therapeutic applications are typically collected from conditioned media of cultured cells. However, the number of EVs secreted by the cells is limited. Thus, it is critical to devise new strategies for the large-scale production of EVs. Here, we discussed the strategies utilized by researchers for the scalable production of EVs. Techniques such as bioreactors, mechanical stimulation, electrical stimulation, thermal stimulation, magnetic field stimulation, topographic clue, hypoxia, serum deprivation, pH modification, exposure to small molecules, exposure to nanoparticles, increasing the intracellular calcium concentration, and genetic modification have been used to improve the secretion of EVs by cultured cells. In addition, nitrogen cavitation, porous membrane extrusion, and sonication have been utilized to prepare EV-mimetic nanovesicles that share many characteristics with naturally secreted EVs. Apart from inducing EV production, these upscaling interventions have also been reported to modify the EVs’ cargo and thus their functionality and therapeutic potential. In summary, it is imperative to identify a reliable upscaling technique that can produce large quantities of EVs consistently. Ideally, the produced EVs should also possess cargo with improved therapeutic potential.

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“…These studies provide evidence that miRNA transfer between immune cells facilitate the regulation of inflammatory responses ( 161 ). Dendritic cell derived EVs have been demonstrated to regulate innate immunity by EV-mediated transfer of miRNAs among DCs contributes to enhance their mutual activation during inflammation ( 162 , 163 ). DC derived EVs with CD86, a costimulatory molecule, activates T cells through direct or semi-direct pathway ( 3 , 164 ).…”

Section: Microrna’s In Evs and Their Role In Immune Responsementioning

confidence: 99%

Extracellular Vesicles Mediate Immune Responses to Tissue-Associated Self-Antigens: Role in Solid Organ Transplantations

et al. 2022

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Transplantation is a treatment option for patients diagnosed with end-stage organ diseases; however, long-term graft survival is affected by rejection of the transplanted organ by immune and nonimmune responses. Several studies have demonstrated that both acute and chronic rejection can occur after transplantation of kidney, heart, and lungs. A strong correlation has been reported between de novo synthesis of donor-specific antibodies (HLA-DSAs) and development of both acute and chronic rejection; however, some transplant recipients with chronic rejection do not have detectable HLA-DSAs. Studies of sera from such patients demonstrate that immune responses to tissue-associated antigens (TaAgs) may also play an important role in the development of chronic rejection, either alone or in combination with HLA-DSAs. The synergistic effect between HLA-DSAs and antibodies to TaAgs is being established, but the underlying mechanism is yet to be defined. We hypothesize that HLA-DSAs damage the transplanted donor organ resulting in stress and leading to the release of extracellular vesicles, which contribute to chronic rejection. These vesicles express both donor human leukocyte antigen (HLA) and non-HLA TaAgs, which can activate antigen-presenting cells and lead to immune responses and development of antibodies to both donor HLA and non-HLA tissue-associated Ags. Extracellular vesicles (EVs) are released by cells under many circumstances due to both physiological and pathological conditions. Primarily employing clinical specimens obtained from human lung transplant recipients undergoing acute or chronic rejection, our group has demonstrated that circulating extracellular vesicles display both mismatched donor HLA molecules and lung-associated Ags (collagen-V and K-alpha 1 tubulin). This review focuses on recent studies demonstrating an important role of antibodies to tissue-associated Ags in the rejection of transplanted organs, particularly chronic rejection. We will also discuss the important role of extracellular vesicles released from transplanted organs in cross-talk between alloimmunity and autoimmunity to tissue-associated Ags after solid organ transplantation.

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Small Extracellular Vesicles in Transplant Rejection

Cited by 20 publications

References 182 publications

The roles of extracellular vesicles in the immune system

The roles of extracellular vesicles in the immune system

Scalable Production of Extracellular Vesicles and Its Therapeutic Values: A Review

Extracellular Vesicles Mediate Immune Responses to Tissue-Associated Self-Antigens: Role in Solid Organ Transplantations

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