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Zheng J, Wang H, Ge L. Advances in Exosome Research: Multifaceted Roles in Myeloid Leukemia Progression and Therapy. J Biochem Mol Toxicol 2025; 39:e70315. [PMID: 40400316 DOI: 10.1002/jbt.70315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2025] [Revised: 03/31/2025] [Accepted: 05/09/2025] [Indexed: 05/23/2025]
Abstract
Recent advancements in exosome research have revealed their crucial role in myeloid leukemia, encompassing chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). Exosomes, small extracellular vesicles released by various cells, play a significant role in intercellular communication and impact key cellular processes such as growth, proliferation, angiogenesis, survival, and apoptosis. In leukemia, exosomes contribute to disease progression and therapeutic resistance by facilitating immune evasion, enhancing tumor cell proliferation, and promoting angiogenesis. For instance, exosomes derived from CML cells can transfer drug resistance to sensitive cells, and some exosomes derived from AML patients contain cytokines like TGF-β1 that inhibit immune cell activity. Exosomes also influence tumor organotropism by interacting with extracellular matrix molecules and modifying the tumor microenvironment. Despite their high potential, clinical applications of exosomes are limited. Their natural nanoparticle properties-such as adaptability, biodegradability, low toxicity, and the ability to cross biological barriers-make them promising candidates for targeted drug delivery and personalized medicine. Further research is necessary to scale up exosome production and harness their full therapeutic potential. By integrating advancements in exosome biology with innovative therapeutic strategies, there is significant potential for improved management and treatment of leukemia.
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MESH Headings
- Humans
- Exosomes/metabolism
- Exosomes/pathology
- Tumor Microenvironment
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy
- Animals
- Leukemia, Myeloid, Acute/pathology
- Leukemia, Myeloid, Acute/metabolism
- Leukemia, Myeloid, Acute/therapy
- Disease Progression
- Drug Resistance, Neoplasm
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Affiliation(s)
- Jianlan Zheng
- Nephrology Center,Department of Nephrology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, PR China
| | - Huafang Wang
- Cancer center, Department of Hematology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, PR China
| | - Lili Ge
- Department of Nursing, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, PR China
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2
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Tao K, Tao K, Wang J. The potential mechanisms of extracellular vesicles in transfusion-related adverse reactions: Recent advances. Transfus Clin Biol 2025; 32:205-227. [PMID: 40180029 DOI: 10.1016/j.tracli.2025.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 03/15/2025] [Accepted: 03/25/2025] [Indexed: 04/05/2025]
Abstract
Blood transfusion is an irreplaceable clinical treatment. Blood components are differentiated and stored according to specific guidelines. Storage temperatures and times vary depending on the blood component, but they all release extracellular vesicles (EVs) during storage. Although blood transfusions can be life-saving, they can also cause many adverse transfusion reactions, among which the effects of EVs are of increasing interest to researchers. EVs are submicron particles that vary in size, composition, and surface biomarkers, are encapsulated by a lipid bilayer, and are not capable of self-replication. EVs released by blood cells are important contributors to pathophysiologic states through proinflammatory, coagulant, and immunosuppressive effects, which in turn promote or inhibit the associated disease phenotype. Therefore, this review explores the potential mechanisms of hematopoietic-derived EVs in transfusion-associated adverse reactions and discusses the potential of the latest proteomics tools to be applied to the analysis of EVs in the field of transfusion medicine with a view to reducing the risk of blood transfusion.
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Affiliation(s)
- Keyi Tao
- Panzhihua University, Panzhihua 617000 Sichuan, China
| | - Keran Tao
- Institute of Medicine and Nursing, Hubei University of Medicine, Shiyan 442000 Hubei, China
| | - Jing Wang
- Southwest Medical University, Luzhou 646000 Sichuan, China; Department of Blood Transfusion, The Affiliated Hospital of Southwest Medical University, Luzhou Sichuan, 646000 China.
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Abida, Alhuthali HM, Alshehri JM, Alkathiri A, Almaghrabi ROM, Alsaeed SS, Albebi SAH, Almethn RM, Alfuraydi BA, Alharbi SB, Kamal M, Imran M. Exosomes in infectious diseases: insights into leishmaniasis pathogenesis, immune modulation, and therapeutic potential. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:4913-4931. [PMID: 39702600 DOI: 10.1007/s00210-024-03702-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 12/02/2024] [Indexed: 12/21/2024]
Abstract
Leishmaniasis continues to be a critical international health issue due to the scarcity of efficient treatment and the development of drug tolerance. New developments in the research of extracellular vesicles (EVs), especially exosomes, have revealed novel disease management approaches. Exosomes are small vesicles that transport lipids, nucleic acids, and proteins in cell signalling. Its biogenesis depends on several cellular processes, and their functions in immune response, encompassing innate and adaptive immunity, underline their function in the pathogen-host interface. Exosomes play a significant role in the pathogenesis of some parasitic infections, especially Leishmaniasis, by helping parasites escape host immunity and promote disease progression. This article explains that in the framework of parasitic diseases, exosomes can act as master regulators that define the pathogenesis of the disease, as illustrated by the engagement of exosomes in the Leishmaniasis parasite and immune escape processes. Based on many published articles on Leishmaniasis, this review aims to summarize the biogenesis of exosomes, the properties of the cargo in exosomes, and the modulation of immune responses. We delve deeper into the prospect of using exosomes for the therapy of Leishmaniasis based on the possibility of using these extracellular vesicles for drug delivery and as diagnostic and prognostic biomarkers. Lastly, we focus on the recent research perspectives and future developments, underlining the necessity to continue the investigation of exosome-mediated approaches in Leishmaniasis treatment. Thus, this review intends to draw attention to exosomes as a bright new perspective in the battle against this disabling affliction.
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Affiliation(s)
- Abida
- Department of Pharmaceutical Chemistry, College of Pharmacy, Northern Border University, 91911, Rafha, Saudi Arabia
| | - Hayaa M Alhuthali
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, 21944, Taif, Saudi Arabia
| | - Jawaher Mohammad Alshehri
- Optometry Department, Faculty of Applied Medical Sciences, Albaha University, 65431, Albaha, Saudi Arabia
| | - Afnan Alkathiri
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Albaha University, 65431, Albaha, Saudi Arabia
| | - Ruba Omar M Almaghrabi
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Albaha University, 65431, Albaha, Saudi Arabia
| | | | | | | | | | | | - Mehnaz Kamal
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, 11942, Al-Kharj, Saudi Arabia
| | - Mohd Imran
- Department of Pharmaceutical Chemistry, College of Pharmacy, Northern Border University, 91911, Rafha, Saudi Arabia.
- Center for Health Research, Northern Border University, Arar, Saudi Arabia.
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Cheema NA, Castagna A, Ambrosani F, Argentino G, Friso S, Zurlo M, Beri R, Maule M, Vaia R, Senna G, Caminati M. Extracellular Vesicles in Asthma: Intercellular Cross-Talk in TH2 Inflammation. Cells 2025; 14:542. [PMID: 40214495 PMCID: PMC11989134 DOI: 10.3390/cells14070542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 03/26/2025] [Accepted: 03/31/2025] [Indexed: 04/14/2025] Open
Abstract
Asthma is a complex, multifactorial inflammatory disorder of the airways, characterized by recurrent symptoms and variable airflow obstruction. So far, two main asthma endotypes have been identified, type 2 (T2)-high or T2-low, based on the underlying immunological mechanisms. Recently, extracellular vesicles (EVs), particularly exosomes, have gained increasing attention due to their pivotal role in intercellular communication and distal signaling modulation. In the context of asthma pathobiology, an increasing amount of experimental evidence suggests that EVs secreted by eosinophils, mast cells, dendritic cells, T cells, neutrophils, macrophages, and epithelial cells contribute to disease modulation. This review explores the role of EVs in profiling the molecular signatures of T2-high and T2-low asthma, offering novel perspectives on disease mechanisms and potential therapeutic targets.
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Affiliation(s)
- Naila Arif Cheema
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
| | - Annalisa Castagna
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
| | - Francesca Ambrosani
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
| | - Giuseppe Argentino
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
| | - Simonetta Friso
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
| | - Marco Zurlo
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
- Allergy Unit and Asthma Center, Verona Integrated University Hospital, 37126 Verona, Italy
| | - Ruggero Beri
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
| | - Matteo Maule
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
- Allergy Unit and Asthma Center, Verona Integrated University Hospital, 37126 Verona, Italy
| | - Rachele Vaia
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
- Allergy Unit and Asthma Center, Verona Integrated University Hospital, 37126 Verona, Italy
| | - Gianenrico Senna
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
- Allergy Unit and Asthma Center, Verona Integrated University Hospital, 37126 Verona, Italy
| | - Marco Caminati
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
- Allergy Unit and Asthma Center, Verona Integrated University Hospital, 37126 Verona, Italy
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Meng Y, Yao Z, Ke X, Hu M, Ren H, Gao S, Zhang H. Extracellular vesicles-based vaccines: Emerging immunotherapies against cancer. J Control Release 2025; 378:438-459. [PMID: 39667569 DOI: 10.1016/j.jconrel.2024.12.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 12/03/2024] [Accepted: 12/05/2024] [Indexed: 12/14/2024]
Abstract
Cancer vaccines are promising therapeutic approaches to enhance specific T-cell immunity against most solid tumors. By stimulating anti-tumor immunity, clearing minimal residual disease, and minimizing adverse effects, these vaccines target tumor cells and are effective when combined with immune checkpoint blockade or other immunotherapies. However, the development of tumor cell-based vaccines faces quality issues due to poor immunogenicity, tumor heterogeneity, a suppressive tumor immune microenvironment, and ineffective delivery methods. In contrast, extracellular vesicles (EVs), naturally released by cells, are considered the ideal drug carriers and vaccine platforms. EVs offer highly organ-specific targeting, induce broader and more effective immune responses, and demonstrate superior tissue delivery ability. The development of EV vaccines is crucial for advancing cancer immunotherapy. Compared to cell-based vaccines, EV vaccines produced under Good Manufacturing Practices (GMP) offer advantages such as high safety, ease of preservation and transport, and a wide range of sources. This review summarizes the latest research findings on EV vaccine and potential applications in this field. It also highlights novel neoantigens for the development of EV vaccines against cancer.
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Affiliation(s)
- Yuhua Meng
- Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China; State Key Laboratory of Bioactive Molecules and Druggability Assessment, MOE Key Laboratory of Tumor Molecular Biology, and Institute of Precision Cancer Medicine and Pathology, School of Medicine, Jinan University, Guangzhou, Guangdong, China
| | - Zhimeng Yao
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, MOE Key Laboratory of Tumor Molecular Biology, and Institute of Precision Cancer Medicine and Pathology, School of Medicine, Jinan University, Guangzhou, Guangdong, China; Department of Urology Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Xiurong Ke
- Department of Surgery, Laboratory for Translational Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Mengyuan Hu
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, MOE Key Laboratory of Tumor Molecular Biology, and Institute of Precision Cancer Medicine and Pathology, School of Medicine, Jinan University, Guangzhou, Guangdong, China
| | - Hongzheng Ren
- Gongli Hospital of Shanghai Pudong New Area, Department of Pathology, Shanghai, China
| | - Shegan Gao
- College of Clinical Medicine, The First Affiliated Hospital of Henan University of Science and Technology, Henan Key Laboratory of Cancer Epigenetics, Luoyang, Henan, China.
| | - Hao Zhang
- Gongli Hospital of Shanghai Pudong New Area, Department of Pathology, Shanghai, China; Department of Pathology, and Institute of Precision Cancer Medicine and Pathology, School of Medicine, State Key Laboratory of Bioactive Molecules and Druggability Assessment, MOE Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, Guangdong, China; Department of Thoracic Surgery and General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
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6
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Abedi A, Moosazadeh Moghaddam M, Kachuei R, Imani Fooladi AA. Exosomes as a Therapeutic Strategy in Cancer: Potential Roles as Drug Carriers and Immune Modulators. Biochim Biophys Acta Rev Cancer 2025; 1880:189238. [PMID: 39674417 DOI: 10.1016/j.bbcan.2024.189238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 12/04/2024] [Accepted: 12/05/2024] [Indexed: 12/16/2024]
Abstract
Exosome-based cancer immunotherapy is advancing quickly on the concept of artificially activating the immune system to combat cancer. They can mechanistically change the tumor microenvironment, increase immune responses, and function as efficient drug delivery vehicles because of their inherent bioactivity, low toxicity, and immunogenicity. Accurate identification of the mechanisms of action of exosomes in tumor environments, along with optimization of their isolation, purification, and characterization methods, is necessary to increase clinical applications. Exosomes can be modified through cargo loading and surface modification to enhance their therapeutic applications, either before or after the donor cells' isolation. These engineered exosomes can directly target tumor cells at the tumor site or indirectly activate innate and adaptive immune responses in the tumor microenvironment. This approach is particularly effective when combined with traditional cancer immunotherapy techniques such as vaccines, immune checkpoints, and CAR-T cells. It can improve anti-tumor responses, induce long-term immunity, and address the limitations of traditional therapies, such as poor penetration in solid tumors and immunosuppressive environments. This review aims to provide a comprehensive and detailed overview of the direct role of engineered exosomes as drug delivery systems and their immunomodulatory effects on tumors as an indirect approach to fighting cancer. Additionally, it will discuss novel immunotherapy options.
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Affiliation(s)
- Azam Abedi
- Tissue Engineering and Regenerative Medicine Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mehrdad Moosazadeh Moghaddam
- Tissue Engineering and Regenerative Medicine Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Reza Kachuei
- Molecular Biology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Abbas Ali Imani Fooladi
- Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
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Li J, Zhou W, Wang H, Huang M, Deng H. Exosomal circular RNAs in tumor microenvironment: An emphasis on signaling pathways and clinical opportunities. MedComm (Beijing) 2024; 5:e70019. [PMID: 39584047 PMCID: PMC11586091 DOI: 10.1002/mco2.70019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 10/21/2024] [Accepted: 10/25/2024] [Indexed: 11/26/2024] Open
Abstract
Exosomes can regulate the malignant progression of tumors by carrying a variety of genetic information and transmitting it to target cells. Recent studies indicate that exosomal circular RNAs (circRNAs) regulate multiple biological processes in carcinogenesis, such as tumor growth, metastasis, epithelial-mesenchymal transition, drug resistance, autophagy, metabolism, angiogenesis, and immune escape. In the tumor microenvironment (TME), exosomal circRNAs can be transferred among tumor cells, endothelial cells, cancer-associated fibroblasts, immune cells, and microbiota, affecting tumor initiation and progression. Due to the high stability and widespread presence of exosomal circRNAs, they hold promise as biomarkers for tumor diagnosis and prognosis prediction in blood and urine. In addition, designing nanoparticles targeting exosomal circRNAs and utilizing exosomal circRNAs derived from immune cells or stem cells provide new strategies for cancer therapy. In this review, we examined the crucial role of exosomal circRNAs in regulating tumor-related signaling pathways and summarized the transmission of exosomal circRNAs between various types of cells and their impact on the TME. Finally, our review highlights the potential of exosomal circRNAs as diagnostic and prognostic prediction biomarkers, as well as suggesting new strategies for clinical therapy.
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Affiliation(s)
- Junshu Li
- Department of Biotherapy, Cancer Center and State Key Laboratory of BiotherapyWest China Hospital, Sichuan UniversityChengduChina
| | - Wencheng Zhou
- Department of Medical AestheticsWest China School of Public Health and West China Fourth HospitalSichuan UniversityChengduChina
| | - Huiling Wang
- Department of Biotherapy, Cancer Center and State Key Laboratory of BiotherapyWest China Hospital, Sichuan UniversityChengduChina
| | - Meijuan Huang
- Division of Thoracic Tumor Multimodality Treatment and Department of Medical OncologyCancer CenterWest China Hospital, Sichuan UniversityChengduChina
| | - Hongxin Deng
- Department of Biotherapy, Cancer Center and State Key Laboratory of BiotherapyWest China Hospital, Sichuan UniversityChengduChina
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Bashir SM, Rizk SM, Nooh MM, Helmy HS. Exosomes Derived from Bone Marrow Dendritic Cells Exhibit Protective and Therapeutic Potential Against Chemically Induced Chronic Pancreatitis in Rats. Inflammation 2024:10.1007/s10753-024-02150-y. [PMID: 39424751 DOI: 10.1007/s10753-024-02150-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 09/10/2024] [Accepted: 09/23/2024] [Indexed: 10/21/2024]
Abstract
BACKGROUND Chronic pancreatitis (CP) is a specific clinical disorder that develops from pancreatic fibrosis and immune cell dysregulation. It has been proposed that bone marrow dendritic cells (BMDCs) exosomes have significant effects on immune regulation. Thus, the current study acquainted the prophylactic and therapeutic effects of exosomes derived from BMDCs on a rat model of CP. MATERIALS AND METHODS BMDCs were prepared and identified, and then the exosomes were isolated by differential ultracentrifugation. Prophylactic and therapeutic effects of exosomes were investigated on L-arginine induced CP model. RESULTS Administration of two tail vein injections of exosomes (200 μg/kg/dose suspended in 0.2 ml PBS) markedly improved the pancreatic function and histology compared to CP group. Moreover, exosomes prominently mitigated the increase in amylase, lipase, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β) and elevated antioxidant enzymes; catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx). CONCLUSION BMDCs exosomes can be considered as a promising candidate, with a high efficacy and stability compared with its parent cell, for management of CP and similar inflammatory diseases.
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Affiliation(s)
- Shaimaa M Bashir
- Department of Biochemistry, Faculty of Pharmacy, October 6 University, Giza, 12585, Egypt.
| | - Sherine M Rizk
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
| | - Mohammed M Nooh
- Department of Biochemistry, Faculty of Pharmacy, October 6 University, Giza, 12585, Egypt
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt
| | - Hebatullah S Helmy
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt
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Lu Y, Zheng J, Lin P, Lin Y, Zheng Y, Mai Z, Chen X, Xia T, Zhao X, Cui L. Tumor Microenvironment-Derived Exosomes: A Double-Edged Sword for Advanced T Cell-Based Immunotherapy. ACS NANO 2024; 18:27230-27260. [PMID: 39319751 DOI: 10.1021/acsnano.4c09190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2024]
Abstract
The tumor microenvironment (TME) plays a crucial role in cancer progression and immune evasion, partially mediated by the activity of the TME-derived exosomes. These extracellular vesicles are pivotal in shaping immune responses through the transfer of proteins, lipids, and nucleic acids between cells, facilitating a complex interplay that promotes tumor growth and metastasis. This review delves into the dual roles of exosomes in the TME, highlighting both their immunosuppressive functions and their emerging therapeutic potential. Exosomes can inhibit T cell function and promote tumor immune escape by carrying immune-modulatory molecules, such as PD-L1, yet they also hold promise for cancer therapy as vehicles for delivering tumor antigens and costimulatory signals. Additionally, the review discusses the intricate crosstalk mediated by exosomes among various cell types within the TME, influencing both cancer progression and responses to immunotherapies. Moreover, this highlights current challenges and future directions. Collectively, elucidating the detailed mechanisms by which TME-derived exosomes mediate T cell function offers a promising avenue for revolutionizing cancer treatment. Understanding these interactions allows for the development of targeted therapies that manipulate exosomal pathways to enhance the immune system's response to tumors.
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Affiliation(s)
- Ye Lu
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong 510280, China
| | - Jiarong Zheng
- Department of Dentistry, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
| | - Pei Lin
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong 510280, China
| | - Yunfan Lin
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong 510280, China
| | - Yucheng Zheng
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong 510280, China
| | - Zizhao Mai
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong 510280, China
| | - Xu Chen
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong 510280, China
| | - Tian Xia
- Division of NanoMedicine, Department of Medicine, University of California Los Angeles, Los Angeles, California 90095, United States
| | - Xinyuan Zhao
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong 510280, China
| | - Li Cui
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong 510280, China
- School of Dentistry, University of California Los Angeles, Los Angeles, California 90095, United States
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10
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Nanru P. Immunomodulatory effects of immune cell-derived extracellular vesicles in melanoma. Front Immunol 2024; 15:1442573. [PMID: 39391320 PMCID: PMC11464304 DOI: 10.3389/fimmu.2024.1442573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 09/04/2024] [Indexed: 10/12/2024] Open
Abstract
Melanoma, recognized as one of the most immunogenic malignancies in humans, holds paramount significance in the realm of immunotherapy. However, the emergence of drug resistance and the occurrence of adverse drug reactions underscore the pressing need to explore increasingly personalized immunotherapeutic modalities. Extracellular Vesicles (EVs), pivotal derivatives of immune cells, assume pivotal roles by encapsulating proteins, lipids, and nucleic acids within bilayer lipid structures, thereby facilitating targeted delivery to other immune cells. This orchestrated process orchestrates critical functions including antigen presentation, immune modulation, and the induction of apoptosis in tumor cells. A burgeoning body of evidence underscores the vast therapeutic potential of EVs in melanoma treatment. This comprehensive review aims to delineate the roles of EVs derived from immune cells such as dendritic cells, natural killer cells, macrophages, and T cells in the context of melanoma patients, thereby furnishing invaluable insights for the future direction of melanoma immunotherapy.
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Affiliation(s)
- Peng Nanru
- Department of Plastic Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou
University, Zhengzhou, China
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11
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Lu J, Zhou H, Chen Y, Xia X, Yang J, Ma J, Tian J, Wang S. Tfh cell-derived small extracellular vesicles exacerbate the severity of collagen-induced arthritis by enhancing B-cell responses. J Autoimmun 2024; 146:103235. [PMID: 38696926 DOI: 10.1016/j.jaut.2024.103235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 03/28/2024] [Accepted: 04/16/2024] [Indexed: 05/04/2024]
Abstract
Soluble components secreted by Tfh cells are critical for the germinal center responses. In this study, we investigated whether Tfh cells could regulate the B-cell response by releasing small extracellular vesicles (sEVs). Our results showed that Tfh cells promote B-cell differentiation and antibody production through sEVs and that CD40L plays a crucial role in Tfh-sEVs function. In addition, increased Tfh-sEVs were found in mice with collagen-induced arthritis (CIA). Adoptive transfer of Tfh cells significantly exacerbated the severity of CIA; however, the effect of Tfh cells on exacerbating the CIA process was significantly diminished after inhibiting sEVs secretion. Moreover, the levels of plasma Tfh-like-sEVs and CD40L expression on Tfh-like-sEVs in RA patients were significantly higher than those in healthy subjects. In summary, Tfh cell-derived sEVs can enhance the B-cell response, and exacerbate the procession of autoimmune arthritis.
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Affiliation(s)
- Jian Lu
- Department of Laboratory Medicine, Affiliated Hospital, Jiangsu University, Zhenjiang, China; Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Huimin Zhou
- Department of Laboratory Medicine, Affiliated Hospital, Jiangsu University, Zhenjiang, China; Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Yuxuan Chen
- Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Xueli Xia
- Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Jun Yang
- Department of Laboratory Medicine, Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
| | - Jie Ma
- Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Jie Tian
- Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China.
| | - Shengjun Wang
- Department of Laboratory Medicine, Affiliated Hospital, Jiangsu University, Zhenjiang, China; Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China; Department of Laboratory Medicine, Affiliated People's Hospital, Jiangsu University, Zhenjiang, China.
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12
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Guan XL, Guan XY, Zhang ZY. Roles and application of exosomes in the development, diagnosis and treatment of gastric cancer. World J Gastrointest Oncol 2024; 16:630-642. [PMID: 38577463 PMCID: PMC10989387 DOI: 10.4251/wjgo.v16.i3.630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Revised: 12/18/2023] [Accepted: 01/15/2024] [Indexed: 03/12/2024] Open
Abstract
As important messengers of intercellular communication, exosomes can regulate local and distant cellular communication by transporting specific exosomal contents and can also promote or suppress the development and progression of gastric cancer (GC) by regulating the growth and proliferation of tumor cells, the tumor-related immune response and tumor angiogenesis. Exosomes transport bioactive molecules including DNA, proteins, and RNA (coding and noncoding) from donor cells to recipient cells, causing reprogramming of the target cells. In this review, we will describe how exosomes regulate the cellular immune response, tumor angiogenesis, proliferation and metastasis of GC cells, and the role and mechanism of exosome-based therapy in human cancer. We will also discuss the potential application value of exosomes as biomarkers in the diagnosis and treatment of GC and their relationship with drug resistance.
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Affiliation(s)
- Xiao-Li Guan
- Department of General Medicine, The Second Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, China
| | - Xiao-Ying Guan
- Department of Pathology, The Second Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, China
| | - Zheng-Yi Zhang
- Department of General Medicine, The Second Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, China
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13
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Daza Zapata AM, Álvarez K, Vásquez Duque G, Palacio J, Rojas López M. Janus kinase inhibitors modify the fatty acid profile of extracellular vesicles and modulate the immune response. Heliyon 2024; 10:e24710. [PMID: 38314280 PMCID: PMC10837569 DOI: 10.1016/j.heliyon.2024.e24710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 01/11/2024] [Accepted: 01/12/2024] [Indexed: 02/06/2024] Open
Abstract
Background Janus kinase inhibitors (jakinibs) are immunomodulators used for treating malignancies, autoimmune diseases, and immunodeficiencies. However, they induce adverse effects such as thrombosis, lymphocytosis, and neutropenia that could be mediated by extracellular vesicles (EVs). These particles are cell membrane-derived structures that transport cellular and environmental molecules and participate in intercellular communication. Jakinibs can modify the content of EVs and enable them to modulate the activity of different components of the immune response. Objective to evaluate the interactions between immune system components of healthy individuals and EVs derived from monocytic and lymphoid lineage cells generated in the presence of baricitinib (BARI) and itacitinib (ITA) and their possible effects. Methods EVs were isolated from monocytes (M) and lymphocytes (L) of healthy individuals, as well as from U937 (U) and Jurkat (J) cells exposed to non-cytotoxic concentrations of BARI, ITA, and dimethyl sulfoxide (DMSO; vehicle control). The binding to and engulfment of EVs by peripheral blood leukocytes of healthy individuals were analyzed by flow cytometry using CFSE-stained EVs and anti-CD45-PeCy7 mAb-labeled whole blood. The effect of EVs on respiratory burst, T-cell activation and proliferation, cytokine synthesis, and platelet aggregation was evaluated. Respiratory burst was assessed in PMA-stimulated neutrophils by the dihydrorhodamine (DHR) test and flow cytometry. T-cell activation and proliferation and cytokine production were assessed in CFSE-stained PBMC cultures stimulated with PHA; expression of the T-cell activation markers CD25 and CD69 and T-cell proliferation were analyzed by flow cytometry, and the cytokine levels were quantified in culture supernatants by Luminex assays. Platelet aggregation was analyzed in platelet-rich plasma (PRP) samples by light transmission aggregometry. The EVs' fatty acid (FA) profile was analyzed using methyl ester derivatization followed by gas chromatography. Results ITA exposure during the generation of EVs modified the size of the EVs released; however, treatment with DMSO and BARI did not alter the size of EVs generated from U937 and Jurkat cells. Circulating neutrophils, lymphocytes, and monocytes showed a 2-fold greater tendency to internalize ITA-U-EVs than their respective DMSO control. The neutrophil respiratory burst was attenuated in greater extent by M-EVs than by L-EVs. Autologous ITA-M-EVs reduced T-cell proliferation by decreasing IL-2 levels and CD25 expression independently of CD69. A higher accumulation of pro-inflammatory cytokines was observed in PHA-stimulated PBMC cultures exposed to M-EVs than to L-EVs; this difference may be related to the higher myristate content of M-EVs. Platelet aggregation increased in the presence of ITA-L/M-EVs by a mechanism presumably dependent on the high arachidonic acid content of the vesicles. Conclusions Cellular origin and jakinib exposure modify the FA profile of EVs, enabling them, in turn, to modulate neutrophil respiratory burst, T-cell proliferation, and platelet aggregation. The increased T-cell proliferation induced by BARI-L/M-EVs could explain the lymphocytosis observed in patients treated with BARI. The higher proportion of arachidonic acid in the FA content of ITA-L/M-EVs could be related to the thrombosis described in patients treated with ITA. EVs also induced a decrease in the respiratory burst of neutrophils.
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Affiliation(s)
- Ana María Daza Zapata
- Grupo de Inmunología Celular e Inmunogenética, Sede de Investigación Universitaria (SIU), Universidad de Antioquia (UDEA), Medellín, Colombia
| | - Karen Álvarez
- Grupo de Inmunología Celular e Inmunogenética, Sede de Investigación Universitaria (SIU), Universidad de Antioquia (UDEA), Medellín, Colombia
| | - Gloria Vásquez Duque
- Grupo de Inmunología Celular e Inmunogenética, Sede de Investigación Universitaria (SIU), Universidad de Antioquia (UDEA), Medellín, Colombia
| | - Juliana Palacio
- Grupo De Investigación Ciencia de Los Materiales, Instituto de Química, Facultad de Ciencias Exactas Y Naturales, Universidad de Antioquia (UdeA), Calle 70 No. 52-21, Colombia
- Universidad Nacional de Colombia,SedeMedellín, Escuela de Química- Carrera 65 A No 59A-110, Medellín, 4309000, Colombia
| | - Mauricio Rojas López
- Grupo de Inmunología Celular e Inmunogenética, Sede de Investigación Universitaria (SIU), Universidad de Antioquia (UDEA), Medellín, Colombia
- Unidad de Citometría de Flujo, Sede de Investigación Universitaria (SIU), Universidad de Antioquia (UDEA), Medellín, Colombia
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14
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A J, S S S, K S, T S M. Extracellular vesicles in bacterial and fungal diseases - Pathogenesis to diagnostic biomarkers. Virulence 2023; 14:2180934. [PMID: 36794396 PMCID: PMC10012962 DOI: 10.1080/21505594.2023.2180934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/17/2023] Open
Abstract
Intercellular communication among microbes plays an important role in disease exacerbation. Recent advances have described small vesicles, termed as "extracellular vesicles" (EVs), previously disregarded as "cellular dust" to be vital in the intracellular and intercellular communication in host-microbe interactions. These signals have been known to initiate host damage and transfer of a variety of cargo including proteins, lipid particles, DNA, mRNA, and miRNAs. Microbial EVs, referred to generally as "membrane vesicles" (MVs), play a key role in disease exacerbation suggesting their importance in pathogenicity. Host EVs help coordinate antimicrobial responses and prime the immune cells for pathogen attack. Hence EVs with their central role in microbe-host communication, may serve as important diagnostic biomarkers of microbial pathogenesis. In this review, we summarize current research regarding the roles of EVs as markers of microbial pathogenesis with specific focus on their interaction with host immune defence and their potential as diagnostic biomarkers in disease conditions.
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Affiliation(s)
- Jnana A
- Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India
| | - Sadiya S S
- Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India
| | - Satyamoorthy K
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India
| | - Murali T S
- Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India
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15
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Habib A, Liang Y, Zhu N. Exosomes multifunctional roles in HIV-1: insight into the immune regulation, vaccine development and current progress in delivery system. Front Immunol 2023; 14:1249133. [PMID: 37965312 PMCID: PMC10642161 DOI: 10.3389/fimmu.2023.1249133] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 10/17/2023] [Indexed: 11/16/2023] Open
Abstract
Human Immunodeficiency Virus (HIV-1) is known to establish a persistent latent infection. The use of combination antiretroviral therapy (cART) can effectively reduce the viral load, but the treatment can be costly and may lead to the development of drug resistance and life-shortening side effects. It is important to develop an ideal and safer in vivo target therapy that will effectively block viral replication and expression in the body. Exosomes have recently emerged as a promising drug delivery vehicle due to their low immunogenicity, nanoscale size (30-150nm), high biocompatibility, and stability in the targeted area. Exosomes, which are genetically produced by different types of cells such as dendritic cells, neurons, T and B cells, epithelial cells, tumor cells, and mast cells, are designed for efficient delivery to targeted cells. In this article, we review and highlight recent developments in the strategy and application of exosome-based HIV-1 vaccines. We also discuss the use of exosome-based antigen delivery systems in vaccine development. HIV-1 antigen can be loaded into exosomes, and this modified cargo can be delivered to target cells or tissues through different loading approaches. This review also discusses the immunological prospects of exosomes and their role as biomarkers in disease progression. However, there are significant administrative and technological obstacles that need to be overcome to fully harness the potential of exosome drug delivery systems.
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Affiliation(s)
- Arslan Habib
- Laboratory of Molecular Immunology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Yulai Liang
- Laboratory of Molecular Immunology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Naishuo Zhu
- Laboratory of Molecular Immunology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
- Institute of Biomedical Sciences, School of Life Sciences, Fudan University, Shanghai, China
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16
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Lin W, Lin Y, Chao H, Lin Y, Hwang W. Haematopoietic cell-derived exosomes in cancer development and therapeutics: From basic science to clinical practice. Clin Transl Med 2023; 13:e1448. [PMID: 37830387 PMCID: PMC10571015 DOI: 10.1002/ctm2.1448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 09/22/2023] [Accepted: 10/01/2023] [Indexed: 10/14/2023] Open
Abstract
BACKGROUND The tumour microenvironment (TME) is a specialised niche involving intercellular communication among cancer cells and various host cells. Among the host cells, the quantity and quality of immune cells within the TME play essential roles in cancer development and management. The immunologically suppressive, so-called 'cold' TME established by a series of tumour-host interactions, including generating immunosuppressive cytokines and recruiting regulatory host immune cells, is associated with resistance to therapies and worse clinical outcomes. MAIN BODY Various therapeutic approaches have been used to target the cold TME, including immune checkpoint blockade therapy and adoptive T-cell transfer. A promising, less explored therapeutic strategy involves targeting TME-associated exosomes. Exosomes are nanometer-sized, extracellular vesicles that transfer material from donor to recipient cells. These particles can reprogram the recipient cells and modulate the TME. In particular, exosomes from haematopoietic cells are known to promote or suppress cancer progression under specific conditions. Understanding the effects of haematopoietic cell-secreted exosomes may foster the development of therapeutic exosomes (tExos) for personalised cancer treatment. However, the development of exosome-based therapies has unique challenges, including scalable production, purification, storage and delivery of exosomes and controlling batch variations. Clinical trials are being conducted to verify the safety, feasibility, availability and efficacy of tExos. CONCLUSION This review summarises our understanding of how haematopoietic cell-secreted exosomes regulate the TME and antitumour immunity and highlights present challenges and solutions for haematopoietic cell-derived exosome-based therapies.
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Affiliation(s)
- Wen‐Chun Lin
- Department of Biotechnology and Laboratory Science in MedicineNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - You‐Tong Lin
- Department of Biotechnology and Laboratory Science in MedicineNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Hui‐Ching Chao
- Department of Biotechnology and Laboratory Science in MedicineNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Yen‐Yu Lin
- Department of Pathology, Fu Jen Catholic University HospitalFu Jen Catholic UniversityNew Taipei CityTaiwan
- School of Medicine, College of MedicineFu Jen Catholic UniversityNew Taipei CityTaiwan
| | - Wei‐Lun Hwang
- Department of Biotechnology and Laboratory Science in MedicineNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
- Cancer and Immunology Research CenterNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
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17
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Moya-Guzmán MJ, de Solminihac J, Padilla C, Rojas C, Pinto C, Himmel T, Pino-Lagos K. Extracellular Vesicles from Immune Cells: A Biomedical Perspective. Int J Mol Sci 2023; 24:13775. [PMID: 37762077 PMCID: PMC10531060 DOI: 10.3390/ijms241813775] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 09/04/2023] [Accepted: 09/05/2023] [Indexed: 09/29/2023] Open
Abstract
Research on the role of extracellular vesicles (sEV) in physiology has demonstrated their undoubted importance in processes such as the transportation of molecules with significance for cell metabolism, cell communication, and the regulation of mechanisms such as cell differentiation, inflammation, and immunity. Although the role of EVs in the immune response is actively investigated, there is little literature revising, in a comprehensive manner, the role of small EVs produced by immune cells. Here, we present a review of studies reporting the release of sEV by different types of leukocytes and the implications of such observations on cellular homeostasis. We also discuss the function of immune cell-derived sEV and their relationship with pathological states, highlighting their potential application in the biomedical field.
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Affiliation(s)
| | | | | | | | | | | | - Karina Pino-Lagos
- Centro de Investigación e Innovación Biomédica, Facultad de Medicina, Universidad de los Andes, Av. Plaza 2501, Las Condes, Santiago 755000, Chile
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18
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Mukherjee AG, Wanjari UR, Gopalakrishnan AV, Bradu P, Biswas A, Ganesan R, Renu K, Dey A, Vellingiri B, El Allali A, Alsamman AM, Zayed H, George Priya Doss C. Evolving strategies and application of proteins and peptide therapeutics in cancer treatment. Biomed Pharmacother 2023; 163:114832. [PMID: 37150032 DOI: 10.1016/j.biopha.2023.114832] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 04/18/2023] [Accepted: 04/30/2023] [Indexed: 05/09/2023] Open
Abstract
Several proteins and peptides have therapeutic potential and can be used for cancer therapy. By binding to cell surface receptors and other indicators uniquely linked with or overexpressed on tumors compared to healthy tissue, protein biologics enhance the active targeting of cancer cells, as opposed to the passive targeting of cells by conventional small-molecule chemotherapeutics. This study focuses on peptide medications that exist to slow or stop tumor growth and the spread of cancer, demonstrating the therapeutic potential of peptides in cancer treatment. As an alternative to standard chemotherapy, peptides that selectively kill cancer cells while sparing healthy tissue are developing. A mountain of clinical evidence supports the efficacy of peptide-based cancer vaccines. Since a single treatment technique may not be sufficient to produce favourable results in the fight against cancer, combination therapy is emerging as an effective option to generate synergistic benefits. One example of this new area is the use of anticancer peptides in combination with nonpeptidic cytotoxic drugs or the combination of immunotherapy with conventional therapies like radiation and chemotherapy. This review focuses on the different natural and synthetic peptides obtained and researched. Discoveries, manufacture, and modifications of peptide drugs, as well as their contemporary applications, are summarized in this review. We also discuss the benefits and difficulties of potential advances in therapeutic peptides.
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Affiliation(s)
- Anirban Goutam Mukherjee
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, India
| | - Uddesh Ramesh Wanjari
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, India
| | - Abilash Valsala Gopalakrishnan
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, India.
| | - Pragya Bradu
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, India
| | - Antara Biswas
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, India
| | - Raja Ganesan
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 24252, South Korea
| | - Kaviyarasi Renu
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600077 Tamil Nadu, India
| | - Abhijit Dey
- Department of Life Sciences, Presidency University, Kolkata, West Bengal 700073, India
| | - Balachandar Vellingiri
- Stem cell and Regenerative Medicine/Translational Research, Department of Zoology, School of Basic Sciences, Central University of Punjab (CUPB), Bathinda 151401, Punjab, India
| | - Achraf El Allali
- African Genome Center, Mohammed VI Polytechnic University, Ben Guerir, Morocco.
| | - Alsamman M Alsamman
- Department of Genome Mapping, Molecular Genetics, and Genome Mapping Laboratory, Agricultural Genetic Engineering Research Institute, Giza, Egypt
| | - Hatem Zayed
- Department of Biomedical Sciences College of Health Sciences, QU Health, Qatar University, Doha, Qatar
| | - C George Priya Doss
- Department of Integrative Biology, School of BioSciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
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19
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Zhang E, Phan P, Zhao Z. Cellular nanovesicles for therapeutic immunomodulation: A perspective on engineering strategies and new advances. Acta Pharm Sin B 2023; 13:1789-1827. [PMID: 37250173 PMCID: PMC10213819 DOI: 10.1016/j.apsb.2022.08.020] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 07/11/2022] [Accepted: 07/28/2022] [Indexed: 02/08/2023] Open
Abstract
Cellular nanovesicles which are referred to as cell-derived, nanosized lipid bilayer structures, have emerged as a promising platform for regulating immune responses. Owing to their outstanding advantages such as high biocompatibility, prominent structural stability, and high loading capacity, cellular nanovesicles are suitable for delivering various immunomodulatory molecules, such as small molecules, nucleic acids, peptides, and proteins. Immunomodulation induced by cellular nanovesicles has been exploited to modulate immune cell behaviors, which is considered as a novel cell-free immunotherapeutic strategy for the prevention and treatment of diverse diseases. Here we review emerging concepts and new advances in leveraging cellular nanovesicles to activate or suppress immune responses, with the aim to explicate their applications for immunomodulation. We overview the general considerations and principles for the design of engineered cellular nanovesicles with tailored immunomodulatory activities. We also discuss new advances in engineering cellular nanovesicles as immunotherapies for treating major diseases.
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Affiliation(s)
- Endong Zhang
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois Chicago, Chicago, IL 60612, USA
| | - Philana Phan
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois Chicago, Chicago, IL 60612, USA
| | - Zongmin Zhao
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois Chicago, Chicago, IL 60612, USA
- Translational Oncology Program, University of Illinois Cancer Center, Chicago, IL 60612, USA
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20
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Lopes D, Lopes J, Pereira-Silva M, Peixoto D, Rabiee N, Veiga F, Moradi O, Guo ZH, Wang XD, Conde J, Makvandi P, Paiva-Santos AC. Bioengineered exosomal-membrane-camouflaged abiotic nanocarriers: neurodegenerative diseases, tissue engineering and regenerative medicine. Mil Med Res 2023; 10:19. [PMID: 37101293 PMCID: PMC10134679 DOI: 10.1186/s40779-023-00453-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 04/07/2023] [Indexed: 04/28/2023] Open
Abstract
A bio-inspired strategy has recently been developed for camouflaging nanocarriers with biomembranes, such as natural cell membranes or subcellular structure-derived membranes. This strategy endows cloaked nanomaterials with improved interfacial properties, superior cell targeting, immune evasion potential, and prolonged duration of systemic circulation. Here, we summarize recent advances in the production and application of exosomal membrane-coated nanomaterials. The structure, properties, and manner in which exosomes communicate with cells are first reviewed. This is followed by a discussion of the types of exosomes and their fabrication methods. We then discuss the applications of biomimetic exosomes and membrane-cloaked nanocarriers in tissue engineering, regenerative medicine, imaging, and the treatment of neurodegenerative diseases. Finally, we appraise the current challenges associated with the clinical translation of biomimetic exosomal membrane-surface-engineered nanovehicles and evaluate the future of this technology.
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Affiliation(s)
- Daniela Lopes
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal
| | - Joana Lopes
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal
| | - Miguel Pereira-Silva
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal
| | - Diana Peixoto
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal
| | - Navid Rabiee
- School of Engineering, Macquarie University, Sydney, NSW, 2109, Australia
- Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, WA, 6150, Australia
| | - Francisco Veiga
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal
| | - Omid Moradi
- Department of Chemistry, Shahr-e-Qods Branch, Islamic Azad University, Tehran, 374-37515, Iran
| | - Zhan-Hu Guo
- Integrated Composites Laboratory (ICL), Department of Mechanical and Construction Engineering, Northumbria University, Newcastle Upon Tyne, NE1 8ST, UK
| | - Xiang-Dong Wang
- Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University Shanghai Medical College, Shanghai, 200032, China.
| | - João Conde
- Faculdade de Ciências Médicas, NOVA Medical School, Universidade Nova de Lisboa, 1169-056, Lisbon, Portugal
- Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, Faculdade de Ciências Médicas, NOVA Medical School, Universidade Nova de Lisboa, 1169-056, Lisbon, Portugal
| | - Pooyan Makvandi
- School of Engineering, Institute for Bioengineering, The University of Edinburgh, Edinburgh, EH9 3JL, UK.
| | - Ana Cláudia Paiva-Santos
- Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal.
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, 3000-548, Coimbra, Portugal.
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21
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Palacio PL, Pleet ML, Reátegui E, Magaña SM. Emerging role of extracellular vesicles in multiple sclerosis: From cellular surrogates to pathogenic mediators and beyond. J Neuroimmunol 2023; 377:578064. [PMID: 36934525 PMCID: PMC10124134 DOI: 10.1016/j.jneuroim.2023.578064] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 02/06/2023] [Accepted: 03/05/2023] [Indexed: 03/16/2023]
Abstract
Multiple Sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system (CNS) driven by a complex interplay of genetic and environmental factors. While the therapeutic arsenal has expanded significantly for management of relapsing forms of MS, treatment of individuals with progressive MS is suboptimal. This treatment inequality is in part due to an incomplete understanding of pathomechanisms at different stages of the disease-underscoring the critical need for new biomarkers. Extracellular vesicles (EVs) and their bioactive cargo have emerged as endogenous nanoparticles with great theranostic potential-as diagnostic and prognostic biomarkers and ultimately as therapeutic candidates for precision nanotherapeutics. The goals of this review are to: 1) summarize the current data investigating the role of EVs and their bioactive cargo in MS pathogenesis, 2) provide a high level overview of advances and challenges in EV isolation and characterization for translational studies, and 3) conclude with future perspectives on this evolving field.
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Affiliation(s)
- Paola Loreto Palacio
- Department of Pediatrics, Division of Neurology, Nationwide Children's Hospital, Columbus, OH, USA
| | - Michelle L Pleet
- Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
| | - Eduardo Reátegui
- William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA
| | - Setty M Magaña
- Department of Pediatrics, Division of Neurology, Nationwide Children's Hospital, Columbus, OH, USA.
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22
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Jainarayanan AK, Capera J, Céspedes PF, Conceição M, Elanchezhian M, Thomas T, Bonner S, Valvo S, Kurz E, Mahla RS, Berridge G, Hester S, Fischer R, Dustin LB, Wood MJA, Dustin ML. Comparison of different methods for isolating CD8 + T lymphocyte-derived extracellular vesicles and supramolecular attack particles. JOURNAL OF EXTRACELLULAR BIOLOGY 2023; 2:e74. [PMID: 38938417 PMCID: PMC11080737 DOI: 10.1002/jex2.74] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 01/27/2023] [Accepted: 01/30/2023] [Indexed: 06/29/2024]
Abstract
CD8+ T lymphocytes play vital roles in killing infected or deranged host cells, recruiting innate immune cells, and regulating other aspects of immune responses. Like any other cell, CD8+ T cells also produce extracellular particles. These include extracellular vesicles (EVs) and non-vesicular extracellular particles (NVEPs). T cell-derived EVs are proposed to mediate cell-to-cell signalling, especially in the context of inflammatory responses, autoimmunity, and infectious diseases. CD8+ T cells also produce supramolecular attack particles (SMAPs), which are in the same size range as EVs and mediate a component of T cell mediated killing. The isolation technique selected will have a profound effect on yield, purity, biochemical properties and function of T cell-derived particles; making it important to directly compare different approaches. In this study, we compared commonly used techniques (membrane spin filtration, ultracentrifugation, or size exclusion liquid chromatography) to isolate particles from activated human CD8+ T cells and validated our results by single-particle methods, including nanoparticle tracking analysis, flow cytometry, electron microscopy and super-resolution microscopy of the purified sample as well as bulk proteomics and lipidomics analyses to evaluate the quality and nature of enriched T cell-derived particles. Our results show that there is a trade-off between the yield and the quality of T cell-derived particles. Furthermore, the protein and lipid composition of the particles is dramatically impacted by the isolation technique applied. We conclude that from the techniques evaluated, size exclusion liquid chromatography offers the highest quality of T cell derived EVs and SMAPs with acceptable yields for compositional and functional studies.
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Affiliation(s)
- Ashwin K. Jainarayanan
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and, Musculoskeletal SciencesUniversity of OxfordOxfordUK
- Interdisciplinary Bioscience Doctoral Training Program and Exeter CollegeUniversity of OxfordOxfordUK
| | - Jesusa Capera
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and, Musculoskeletal SciencesUniversity of OxfordOxfordUK
| | - Pablo F. Céspedes
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and, Musculoskeletal SciencesUniversity of OxfordOxfordUK
| | | | - Mirudula Elanchezhian
- Department of Biological SciencesIndian Institute of Science Education and ResearchMohaliIndia
| | - Tom Thomas
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and, Musculoskeletal SciencesUniversity of OxfordOxfordUK
- Translational Gastroenterology UnitUniversity of OxfordOxfordUK
- Wellcome Centre for Human GeneticsUniversity of OxfordOxfordUK
| | - Scott Bonner
- Department of PaediatricsUniversity of OxfordOxfordUK
| | - Salvatore Valvo
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and, Musculoskeletal SciencesUniversity of OxfordOxfordUK
| | - Elke Kurz
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and, Musculoskeletal SciencesUniversity of OxfordOxfordUK
| | - Ranjeet Singh Mahla
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and, Musculoskeletal SciencesUniversity of OxfordOxfordUK
| | - Georgina Berridge
- Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | - Svenja Hester
- Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | - Roman Fischer
- Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | - Lynn B. Dustin
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and, Musculoskeletal SciencesUniversity of OxfordOxfordUK
| | - Matthew J. A. Wood
- Department of PaediatricsUniversity of OxfordOxfordUK
- MDUK Oxford Neuromuscular CentreUniversity of OxfordOxfordUK
- Oxford‐Harrington Rare Disease CentreUniversity of OxfordOxfordUK
| | - Michael L. Dustin
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and, Musculoskeletal SciencesUniversity of OxfordOxfordUK
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Mahmoudi F, Hanachi P, Montaseri A. Extracellular vesicles of immune cells; immunomodulatory impacts and therapeutic potentials. Clin Immunol 2023; 248:109237. [PMID: 36669608 DOI: 10.1016/j.clim.2023.109237] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 12/08/2022] [Accepted: 12/28/2022] [Indexed: 01/19/2023]
Abstract
Extracellular vesicles (EVs) are a diverse collection of lipid bilayer-membrane-bound particles which are released from cells into the extracellular space and biologic fluids. In multicellular organisms, these vesicles facilitate the exchange of bioactive compounds such as RNA, DNA, proteins, various metabolites, and lipids between the cells. EVs are produced and released by almost all eukaryotic cells including immune cells and can have immunomodulating effects by either stimulation or suppression of their activities. This immune-modulating feature may provide a promising strategy for treating immune-mediated diseases such as cancer, neurodegenerative diseases, autoimmune disorders and graft-versus-host disease. Moreover, immune cell-derived EVs have received attention as potential biomarkers for being used as diagnostic tools and preventive strategies such as for developing vaccines. In this review, we focus on the EVs produced by different immune cell types, their effects on the immune system, and highlight their potential applications for immunotherapy.
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Affiliation(s)
- Fariba Mahmoudi
- Department of Biotechnology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
| | - Parichehr Hanachi
- Department of Biotechnology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran.
| | - Azadeh Montaseri
- Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology, Sapienza University of Rome, 00161 Rome, Italy
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24
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Exosome-Based Carrier for RNA Delivery: Progress and Challenges. Pharmaceutics 2023; 15:pharmaceutics15020598. [PMID: 36839920 PMCID: PMC9964211 DOI: 10.3390/pharmaceutics15020598] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 02/01/2023] [Accepted: 02/02/2023] [Indexed: 02/12/2023] Open
Abstract
In the last few decades, RNA-based drugs have emerged as a promising candidate to specifically target and modulate disease-relevant genes to cure genetic defects. The key to applying RNA therapy in clinical trials is developing safe and effective delivery systems. Exosomes have been exploited as a promising vehicle for drug delivery due to their nanoscale size, high stability, high biocompatibility, and low immunogenicity. We reviewed and summarized the progress in the strategy and application of exosome-mediated RNA therapy. The challenges of exosomes as a carrier for RNA drug delivery are also elucidated in this article. RNA molecules can be loaded into exosomes and then delivered to targeted cells or tissues via various biochemical or physical approaches. So far, exosome-mediated RNA therapy has shown potential in the treatment of cancer, central nervous system disorders, COVID-19, and other diseases. To further exploit the potential of exosomes for RNA delivery, more efforts should be made to overcome both technological and logistic problems.
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25
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Zhou Q, Wei S, Wang H, Li Y, Fan S, Cao Y, Wang C. T cell-derived exosomes in tumor immune modulation and immunotherapy. Front Immunol 2023; 14:1130033. [PMID: 37153615 PMCID: PMC10157026 DOI: 10.3389/fimmu.2023.1130033] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 03/27/2023] [Indexed: 05/09/2023] Open
Abstract
Exosomes are nanoscale vesicles secreted by most cells and have a phospholipid bilayer structure. Exosomes contain DNA, small RNA, proteins, and other substances that can carry proteins and nucleic acids and participate in communication between cells. T cells are an indispensable part of adaptive immunity, and the functions of T cell-derived exosomes have been widely studied. In the more than three decades since the discovery of exosomes, several studies have revealed that T cell-derived exosomes play a novel role in cell-to-cell signaling, especially in the tumor immune response. In this review, we discuss the function of exosomes derived from different T cell subsets, explore applications in tumor immunotherapy, and consider the associated challenges.
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Affiliation(s)
- Qiujun Zhou
- Department of First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Shenyu Wei
- Department of Hepato-Pancreato-Biliary Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Hui Wang
- Department of First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yuanyuan Li
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China
| | - Shasha Fan
- Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Yi Cao
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China
| | - Chenglei Wang
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China
- *Correspondence: Chenglei Wang,
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26
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Wu M, Wang M, Jia H, Wu P. Extracellular vesicles: emerging anti-cancer drugs and advanced functionalization platforms for cancer therapy. Drug Deliv 2022; 29:2513-2538. [PMID: 35915054 PMCID: PMC9347476 DOI: 10.1080/10717544.2022.2104404] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Increasing evidences show that unmodified extracellular vesicles (EVs) derived from various cells can effectively inhibit the malignant progression of different types of tumors by delivering the bioactive molecules. Therefore, EVs are expected to be developed as emerging anticancer drugs. Meanwhile, unmodified EVs as an advanced and promising nanocarrier that is frequently used in targeted delivery therapeutic cargos and personalized reagents for the treatment and diagnosis of cancer. To improve the efficacy of EV-based treatments, researchers are trying to engineering EVs as an emerging nanomedicine translational therapy platform through biological, physical and chemical approaches, which can be broaden and altered to enhance their therapeutic capability. EVs loaded with therapeutic components such as tumor suppressor drugs, siRNAs, proteins, peptides, and conjugates exhibit significantly enhanced anti-tumor effects. Moreover, the design and preparation of tumor-targeted modified EVs greatly enhance the specificity and effectiveness of tumor therapy, and these strategies are expected to become novel ideas for tumor precision medicine. This review will focus on reviewing the latest research progress of functionalized EVs, clarifying the superior biological functions and powerful therapeutic potential of EVs, for researchers to explore new design concepts based on EVs and build next-generation nanomedicine therapeutic platforms.
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Affiliation(s)
- Manling Wu
- Department of Clinical Laboratory, The First Affiliated Hospital of UST C, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, P.R. China
- Anhui Provincial Children’s Hospital, Hefei, Anhui, P.R. China
| | - Min Wang
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P.R. China
| | - Haoyuan Jia
- Department of Clinical Laboratory, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu, P.R. China
| | - Peipei Wu
- Department of Clinical Laboratory, The First Affiliated Hospital of UST C, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, P.R. China
- Anhui Provincial Children’s Hospital, Hefei, Anhui, P.R. China
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27
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Ma X, Liu B, Fan L, Liu Y, Zhao Y, Ren T, Li Y, Li Y. Native and engineered exosomes for inflammatory disease. NANO RESEARCH 2022; 16:6991-7006. [PMID: 36591564 PMCID: PMC9793369 DOI: 10.1007/s12274-022-5275-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 10/28/2022] [Accepted: 10/31/2022] [Indexed: 05/24/2023]
Abstract
Exosomes are extracellular vesicles which carry specific molecular information from donor cells and act as an intercellular communication vehicle, which have emerged as a novel cell-free strategy for the treatment of many diseases including inflammatory disease. Recently, rising studies have developed exosome-based strategies for novel inflammation therapy due to their biocompatibility and bioactivity. Researchers not only use native exosomes as therapeutic agents for inflammation, but also strive to make up for the natural defects of exosomes through engineering methods to improve and update the property of exosomes for enhanced therapeutic effects. The engineered exosomes can improve cargo-loading efficiency, targeting ability, stability, etc., to achieve combined and diverse treatment strategies in inflammation diseases. Herein, a comprehensive overview of the recent advances in application studies of native and engineered exosomes as well as the engineered methods is provided. Meanwhile, potential application prospects, possible challenges, and the development of clinical researches of exosome treatment strategy are concluded from plentiful examples, which may be able to provide guidance and suggestions for the future research and application of exosomes.
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Affiliation(s)
- Xiaoyi Ma
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200092 China
| | - Bingbing Liu
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200092 China
| | - Limin Fan
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200092 China
| | - Yiqiong Liu
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200092 China
| | - Yuge Zhao
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200092 China
| | - Tianbin Ren
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200092 China
| | - Yan Li
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200092 China
| | - Yongyong Li
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200092 China
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28
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Wang S, Shi Y. Exosomes Derived from Immune Cells: The New Role of Tumor Immune Microenvironment and Tumor Therapy. Int J Nanomedicine 2022; 17:6527-6550. [PMID: 36575698 PMCID: PMC9790146 DOI: 10.2147/ijn.s388604] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Accepted: 12/09/2022] [Indexed: 12/29/2022] Open
Abstract
Exosomes are small vesicles secreted by living cells, with a typical lipid bilayer structure. They carry a variety of proteins, lipids, RNA and other important information, play an important role in the transmission of substances and information between cells, and gradually become a marker for early diagnosis of many diseases and an important tool in drug delivery system. Immune cells are an important part of tumor microenvironment, and they can affect tumor progression by secreting a variety of immunoreactive substances. This review focuses on the effects of various immune cell-derived exosomes on tumor cells, different immune cells and other stromal cells in tumor microenvironment. Exosomes derived from different immune cells can not only reshape a pro-inflammatory microenvironment to inhibit tumor progression, but also promote tumor progression by inhibiting the killing effect of NK cells, CD8+T cells and other cells or promoting tumor cells and immunosuppressive immune cells. In addition, we also discussed that some exosomes derived from immune cells (such as DC, M1 macrophages and neutrophils) play a tumor inhibitory role after being engineered.
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Affiliation(s)
- Shiyang Wang
- Department of Geriatric Surgery, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China
| | - Yue Shi
- Department of Geriatric Surgery, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China,Correspondence: Yue Shi, Department of Geriatric Surgery, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China, Tel +86-13842073309, Email
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29
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Tenchov R, Sasso JM, Wang X, Liaw WS, Chen CA, Zhou QA. Exosomes─Nature's Lipid Nanoparticles, a Rising Star in Drug Delivery and Diagnostics. ACS NANO 2022; 16:17802-17846. [PMID: 36354238 PMCID: PMC9706680 DOI: 10.1021/acsnano.2c08774] [Citation(s) in RCA: 259] [Impact Index Per Article: 86.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 10/21/2022] [Indexed: 05/03/2023]
Abstract
Exosomes are a subgroup of nanosized extracellular vesicles enclosed by a lipid bilayer membrane and secreted by most eukaryotic cells. They represent a route of intercellular communication and participate in a wide variety of physiological and pathological processes. The biological roles of exosomes rely on their bioactive cargos, including proteins, nucleic acids, and lipids, which are delivered to target cells. Their distinctive properties─innate stability, low immunogenicity, biocompatibility, and good biomembrane penetration capacity─allow them to function as superior natural nanocarriers for efficient drug delivery. Another notably favorable clinical application of exosomes is in diagnostics. They hold various biomolecules from host cells, which are indicative of pathophysiological conditions; therefore, they are considered vital for biomarker discovery in clinical diagnostics. Here, we use data from the CAS Content Collection and provide a landscape overview of the current state and delineate trends in research advancement on exosome applications in therapeutics and diagnostics across time, geography, composition, cargo loading, and development pipelines. We discuss exosome composition and pathway, from their biogenesis and secretion from host cells to recipient cell uptake. We assess methods for exosome isolation and purification, their clinical applications in therapy and diagnostics, their development pipelines, the exploration goals of the companies, the assortment of diseases they aim to treat, development stages of their research, and publication trends. We hope this review will be useful for understanding the current knowledge in the field of medical applications of exosomes, in an effort to further solve the remaining challenges in fulfilling their potential.
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Affiliation(s)
- Rumiana Tenchov
- CAS, a Division of the American Chemical
Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United
States
| | - Janet M. Sasso
- CAS, a Division of the American Chemical
Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United
States
| | - Xinmei Wang
- CAS, a Division of the American Chemical
Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United
States
| | - Wen-Shing Liaw
- CAS, a Division of the American Chemical
Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United
States
| | - Chun-An Chen
- CAS, a Division of the American Chemical
Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United
States
| | - Qiongqiong Angela Zhou
- CAS, a Division of the American Chemical
Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United
States
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30
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Alptekin A, Parvin M, Chowdhury HI, Rashid MH, Arbab AS. Engineered exosomes for studies in tumor immunology. Immunol Rev 2022; 312:76-102. [PMID: 35808839 DOI: 10.1111/imr.13107] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 05/27/2022] [Indexed: 12/14/2022]
Abstract
Exosomes are a type of extracellular vesicle (EV) with diameters of 30-150 nm secreted by most of the cells into the extracellular spaces and can alter the microenvironment through cell-to-cell interactions by fusion with the plasma membrane and subsequent endocytosis and release of the cargo. Because of their biocompatibility, low toxicity and immunogenicity, permeability (even through the blood-brain barrier (BBB)), stability in biological fluids, and ability to accumulate in the lesions with higher specificity, investigators have started making designer's exosomes or engineered exosomes to carry biologically active protein on the surface or inside the exosomes as well as using exosomes to carry drugs, micro RNA, and other products to the site of interest. In this review, we have discussed biogenesis, markers, and contents of various exosomes including exosomes of immune cells. We have also discussed the current methods of making engineered and designer's exosomes as well as the use of engineered exosomes targeting different immune cells in the tumors, stroke, as well as at peripheral blood. Genetic engineering and customizing exosomes create an unlimited opportunity to use in diagnosis and treatment. Very little use has been discovered, and we are far away to reach its limits.
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Affiliation(s)
- Ahmet Alptekin
- Georgia Cancer Center, Augusta University, Augusta, Georgia, USA
| | - Mahrima Parvin
- Georgia Cancer Center, Augusta University, Augusta, Georgia, USA
| | | | | | - Ali S Arbab
- Georgia Cancer Center, Augusta University, Augusta, Georgia, USA
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31
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Qian K, Fu W, Li T, Zhao J, Lei C, Hu S. The roles of small extracellular vesicles in cancer and immune regulation and translational potential in cancer therapy. J Exp Clin Cancer Res 2022; 41:286. [PMID: 36167539 PMCID: PMC9513874 DOI: 10.1186/s13046-022-02492-1] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 09/08/2022] [Indexed: 11/23/2022] Open
Abstract
Extracellular vesicles (EVs) facilitate the extracellular transfer of proteins, lipids, and nucleic acids and mediate intercellular communication among multiple cells in the tumour environment. Small extracellular vesicles (sEVs) are defined as EVs range in diameter from approximately 50 to 150 nm. Tumour-derived sEVs (TDsEVs) and immune cell-derived sEVs have significant immunological activities and participate in cancer progression and immune responses. Cancer-specific molecules have been identified on TDsEVs and can function as biomarkers for cancer diagnosis and prognosis, as well as allergens for TDsEVs-based vaccination. Various monocytes, including but not limited to dendritic cells (DCs), B cells, T cells, natural killer (NK) cells, macrophages, and myeloid-derived suppressor cells (MDSCs), secrete sEVs that regulate immune responses in the complex immune network with either protumour or antitumour effects. After engineered modification, sEVs from immune cells and other donor cells can provide improved targeting and biological effects. Combined with their naïve characteristics, these engineered sEVs hold great potential as drug carriers. When used in a variety of cancer therapies, they can adjunctly enhance the safety and antitumor efficacy of multiple therapeutics. In summary, both naïve sEVs in the tumour environment and engineered sEVs with effector cargoes are regarded as showing promising potential for use in cancer diagnostics and therapeutics.
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32
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Khan FH, Reza MJ, Shao YF, Perwez A, Zahra H, Dowlati A, Abbas A. Role of exosomes in lung cancer: A comprehensive insight from immunomodulation to theragnostic applications. Biochim Biophys Acta Rev Cancer 2022; 1877:188776. [PMID: 35961620 DOI: 10.1016/j.bbcan.2022.188776] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 07/18/2022] [Accepted: 08/02/2022] [Indexed: 12/18/2022]
Abstract
Exosomes are 30 to 150 nm-diameter lipid bilayer-enclosed extracellular vesicles that enable cell-to-cell communication through secretion and uptake. The exosomal cargoes contain RNA, lipids, proteins, and metabolites which can be delivered to recipient cells in vivo. In a healthy lung, exosomes facilitate interaction between adaptive and innate immunity and help maintain normal lung physiology. However, tumor-derived exosomes in lung cancer (LC) can, on the other hand, restrict immune cell proliferation, cause apoptosis in activated CD8+ T effector cells, reduce natural killer cell activity, obstruct monocyte differentiation, and promote proliferation of myeloid-derived suppressor and regulatory T cells. In addition, exosomes in the tumor microenvironment may also play a critical role in cancer progression and the development of drug resistance. In this review, we aim to comprehensively examine the current updates on the role of exosomes in lung carcinogenesis and their potential application as a diagnostic, prognostic, and therapeutic tool in lung cancer.
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Affiliation(s)
- Faizan Haider Khan
- Discipline of Pathology, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway, Ireland
| | - Malik Johid Reza
- College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68131, USA
| | - Yusra Fatima Shao
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA
| | - Ahmad Perwez
- Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
| | - Honey Zahra
- Department of Anatomy, King George's Medical University, Lucknow, UP 226003, India
| | - Afshin Dowlati
- Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; University Hospitals Seidman Cancer Center, Cleveland, OH 44106, USA; Developmental Therapeutics Program, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44116, USA.
| | - Ata Abbas
- Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; Developmental Therapeutics Program, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44116, USA.
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33
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Wu F, Gao J, Kang J, Wang X, Niu Q, Liu J, Zhang L. Knowledge Mapping of Exosomes in Autoimmune Diseases: A Bibliometric Analysis (2002–2021). Front Immunol 2022; 13:939433. [PMID: 35935932 PMCID: PMC9353180 DOI: 10.3389/fimmu.2022.939433] [Citation(s) in RCA: 81] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 06/24/2022] [Indexed: 12/14/2022] Open
Abstract
Background Autoimmune diseases (AIDs) are a class of chronic disabling diseases characterized by inflammation and damage to muscles, joints, bones, and internal organs. Recent studies have shown that much progress has been made in the research of exosomes in AIDs. However, there is no bibliometric analysis in this research field. This study aims to provide a comprehensive overview of the knowledge structure and research hotspots of exosomes in AIDs through bibliometrics. Method Publications related to exosomes in AIDs from 2002 to 2021 were searched on the web of science core collection (WoSCC) database. VOSviewers, CiteSpace and R package “bibliometrix” were used to conduct this bibliometric analysis. Results 312 articles from 48 countries led by China and the United States were included. The number of publications related to exosomes in AIDs is increasing year by year. Central South University, Sun Yat Sen University, Tianjin Medical University and University of Pennsylvania are the main research institutions. Frontiers in immunology is the most popular journal in this field, and Journal of Immunology is the most co-cited journal. These publications come from 473 authors among which Ilias Alevizos, Qianjin Lu, Wei Wei, Jim Xiang and Ming Zhao had published the most papers and Clotilde Théry was co-cited most often. Studying the mechanism of endogenous exosomes in the occurrence and development of AIDs and the therapeutic strategy of exogenous exosomes in AIDs are the main topics in this research field. “Mesenchymal stem cells”, “microRNA”, “biomarkers”, “immunomodulation”, and “therapy” are the primary keywords of emerging research hotspots. Conclusion This is the first bibliometric study that comprehensively summarizes the research trends and developments of exosomes in AIDs. This information identifies recent research frontiers and hot directions, which will provide a reference for scholars studying exosomes.
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Affiliation(s)
- Fengping Wu
- School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, China
| | - Jinfang Gao
- Department of Rheumatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
| | - Jie Kang
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Xuexue Wang
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Qing Niu
- School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, China
| | - Jiaxi Liu
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Liyun Zhang
- Department of Rheumatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
- *Correspondence: Liyun Zhang,
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Ruan S, Greenberg Z, Pan X, Zhuang P, Erwin N, He M. Extracellular Vesicles as an Advanced Delivery Biomaterial for Precision Cancer Immunotherapy. Adv Healthc Mater 2022; 11:e2100650. [PMID: 34197051 PMCID: PMC8720116 DOI: 10.1002/adhm.202100650] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 06/22/2021] [Indexed: 12/11/2022]
Abstract
In recent years, cancer immunotherapy has been observed in numerous preclinical and clinical studies for showing benefits. However, due to the unpredictable outcomes and low response rates, novel targeting delivery approaches and modulators are needed for being effective to more broader patient populations and cancer types. Compared to synthetic biomaterials, extracellular vesicles (EVs) specifically open a new avenue for improving the efficacy of cancer immunotherapy by offering targeted and site-specific immunity modulation. In this review, the molecular understanding of EV cargos and surface receptors, which underpin cell targeting specificity and precisely modulating immunogenicity, are discussed. Unique properties of EVs are reviewed in terms of their surface markers, intravesicular contents, intrinsic immunity modulatory functions, and pharmacodynamic behavior in vivo with tumor tissue models, highlighting key indications of improved precision cancer immunotherapy. Novel molecular engineered strategies for reprogramming and directing cancer immunotherapeutics, and their unique challenges are also discussed to illuminate EV's future potential as a cancer immunotherapeutic biomaterial.
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Affiliation(s)
- Shaobo Ruan
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA
| | - Zachary Greenberg
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA
| | - Xiaoshu Pan
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA
| | - Pei Zhuang
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA
| | - Nina Erwin
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA
| | - Mei He
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA
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Abstract
Small extracellular vesicles (sEVs) secreted by most cells carry bioactive macromolecules including proteins, lipids, and nucleic acids for intercellular communication. Given that some immune cell-derived sEVs exhibit anti-cancer properties, these sEVs have received scientific attention for the development of novel anti-cancer immunotherapeutic agents. In this paper, we reviewed the latest advances concerning the biological roles of immune cell-derived sEVs for cancer therapy. sEVs derived from immune cells including dendritic cells (DCs), T cells, natural-killer (NK) cells, and macrophages are good candidates for sEV-based cancer therapy. Besides their role of cancer vaccines, DC-shed sEVs activated cytotoxic lymphocytes and killed tumor cells. sEVs isolated from NK cells and chimeric antigen receptor (CAR) T cells exhibited cytotoxicity against cancer cells. sEVs derived from CD8+ T and CD4+ T cells inhibited cancer-associated cells in tumor microenvironment (TME) and activated B cells, respectively. M1-macrophage-derived sEVs induced M2 to M1 repolarization and also created a pro-inflammatory environment. Hence, these sEVs, via mono or combination therapy, could be considered in the treatment of cancer patients in the future. In addition, sEVs derived from cytokine-stimulated immune cells or sEV engineering could improve their anti-tumor potency.
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Affiliation(s)
- Sung-Jin Choi
- Department of New Biology, DGIST, Daegu 42988, Republic of Korea
| | - Hanchae Cho
- Department of Molecular Medicine, CMRI, Exosome Convergence Research Center (ECRC), School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Kyungmoo Yea
- Department of New Biology, DGIST, Daegu 42988, Republic of Korea
| | - Moon-Chang Baek
- Department of Molecular Medicine, CMRI, Exosome Convergence Research Center (ECRC), School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
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Rana R, Kant R, Kaul D, Sachdev A, Ganguly NK. Integrated view of molecular diagnosis and prognosis of dengue viral infection: future prospect of exosomes biomarkers. Mol Cell Biochem 2022; 477:815-832. [PMID: 35059925 DOI: 10.1007/s11010-021-04326-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 12/03/2021] [Indexed: 10/19/2022]
Abstract
Dengue viruses (DENVs) are the viruses responsible for dengue infection which affects lungs, liver, heart and also other organs of individuals. DENVs consist of the group of four serotypically diverse dengue viruses transmitted in tropical and sub-tropical countries of world. Aedes mosquito is the principal vector which spread the infection from infected person to healthy humans. DENVs can cause different syndromes depending on serotype of virus which range from undifferentiated mild fever to dengue hemorrhagic fever resulting in vascular leakage due to release of cytokine and Dengue shock syndrome with fluid loss and hypotensive shock, or other severe manifestations such as bleeding and organ failure. Increase in dengue cases in pediatric population is a major concern. Transmission of dengue depends on various factors like temperature, rainfall, and distribution of Aedes aegypti mosquitoes. The present review describes a comprehensive overview of dengue, pathophysiology, diagnosis, treatment with an emphasis on potential of exosomes as biomarkers for early prediction of dengue in pediatrics.
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Affiliation(s)
- Rashmi Rana
- Department of Research, Sir Ganga Ram Hospital, New Delhi, 110060, India.
| | - Ravi Kant
- Department of Research, Sir Ganga Ram Hospital, New Delhi, 110060, India
| | - Dinesh Kaul
- Department of Pediatrics, Sir Ganga Ram Hospital, New Delhi, 110060, India
| | - Anil Sachdev
- Department of Pediatrics, Sir Ganga Ram Hospital, New Delhi, 110060, India
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Karami Fath M, Azargoonjahromi A, Jafari N, Mehdi M, Alavi F, Daraei M, Mohammadkhani N, Mueller AL, Brockmueller A, Shakibaei M, Payandeh Z. Exosome application in tumorigenesis: diagnosis and treatment of melanoma. Med Oncol 2022; 39:19. [PMID: 34982284 DOI: 10.1007/s12032-021-01621-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 11/28/2021] [Indexed: 12/12/2022]
Abstract
Melanoma is the most aggressive of skin cancer derived from genetic mutations in the melanocytes. Current therapeutic approaches include surgical resection, chemotherapy, photodynamic therapy, immunotherapy, biochemotherapy, and targeted therapy. However, the efficiency of these strategies may be decreased due to the development of diverse resistance mechanisms. Here, it has been proven that therapeutic monoclonal antibodies (mAbs) can improve the efficiency of melanoma therapies and also, cancer vaccines are another approach for the treatment of melanoma that has already improved clinical outcomes in these patients. The use of antibodies and gene vaccines provides a new perspective in melanoma treatment. Since the tumor microenvironment is another important factor for cancer progression and metastasis, in recent times, a mechanism has been identified to provide an opportunity for melanoma cells to communicate with remote cells. This mechanism is involved by a novel molecular structure, named extracellular vesicles (EVs). Depending on the functional status of origin cells, exosomes contain various cargos and different compositions. In this review, we presented recent progress of exosome applications in the treatment of melanoma. Different aspects of exosome therapy and ongoing efforts in this field will be discussed too.
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Affiliation(s)
- Mohsen Karami Fath
- Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
| | - Ali Azargoonjahromi
- Department of Nursing, School of Nursing and Midwifery, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nafiseh Jafari
- Department of Microbiology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Maryam Mehdi
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Fatemeh Alavi
- Department of Pathobiology, Faculty of Specialized Veterinary Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Mona Daraei
- Pharmacy School, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran
| | - Niloufar Mohammadkhani
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, 1985717443, Tehran, Iran
| | - Anna-Lena Mueller
- Musculoskeletal Research Group and Tumor Biology, Chair of Vegetative Anatomy, Faculty of Medicine, Institute of Anatomy, Ludwig-Maximilian-University Munich, 80336, Munich, Germany
| | - Aranka Brockmueller
- Musculoskeletal Research Group and Tumor Biology, Chair of Vegetative Anatomy, Faculty of Medicine, Institute of Anatomy, Ludwig-Maximilian-University Munich, 80336, Munich, Germany
| | - Mehdi Shakibaei
- Musculoskeletal Research Group and Tumor Biology, Chair of Vegetative Anatomy, Faculty of Medicine, Institute of Anatomy, Ludwig-Maximilian-University Munich, 80336, Munich, Germany.
| | - Zahra Payandeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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Abu N, Rus Bakarurraini NAA. The interweaving relationship between extracellular vesicles and T cells in cancer. Cancer Lett 2021; 530:1-7. [PMID: 34906625 DOI: 10.1016/j.canlet.2021.12.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 11/26/2021] [Accepted: 12/07/2021] [Indexed: 12/21/2022]
Abstract
The interdependency between cancer cells and immune cells is an important link in understanding cancer pathogenesis. T cells are important immune cells that are able to either impede or promote tumor growth. Extracellular vesicles or EVs are membrane-encapsulated vesicles that are released by both cancer and immune cells that can act as communicators. Studies have shown that tumor-derived EVs can interact with immune cells, particularly T cells. Vice versa, T cells-derived EVs have also been shown to possess immunomodulatory roles. Therefore, the purpose of this mini-review is to understand the role of tumor-derived EVs and T-cells derived EVs on cancer immunosuppression especially the interweaving role of different types of EVs and how it affects tumor immunity. We also discuss the role of EVs in different types of T cells namely CD8+, CD4+ Th17 and Treg cells. More importantly, we include the limitations and future directions involving this type of research. This will further elucidate our understanding of the important functions of these tiny mediators.
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Affiliation(s)
- Nadiah Abu
- UKM Medical Molecular Biology Institute (UMBI), UKM Medical Center, 56000, Kuala Lumpur, Malaysia.
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Role and Function of T Cell-Derived Exosomes and Their Therapeutic Value. Mediators Inflamm 2021; 2021:8481013. [PMID: 34803518 PMCID: PMC8604589 DOI: 10.1155/2021/8481013] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 10/29/2021] [Accepted: 11/02/2021] [Indexed: 12/20/2022] Open
Abstract
Exosomes are membrane-bound extracellular vesicles that are produced in the endosomal compartment of most eukaryotic cells. Containing proteins, RNA, and DNA, exosomes mediate intercellular communication between different cell types by transferring their contents and thus are involved in numerous physiological and pathological processes. T cells are an indispensable part of adaptive immunity, and the functions of T cell-derived exosomes have been widely studied. In the more than three decades since the discovery of exosomes, several studies have revealed that T cell-derived exosomes play a novel role in cell-to-cell signaling, especially in inflammatory responses, autoimmunity, and infectious diseases. In this review, we will summarize the function of T cell-derived exosomes and their therapeutic potential.
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40
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Gołębiewska JE, Wardowska A, Pietrowska M, Wojakowska A, Dębska-Ślizień A. Small Extracellular Vesicles in Transplant Rejection. Cells 2021; 10:2989. [PMID: 34831212 PMCID: PMC8616261 DOI: 10.3390/cells10112989] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Revised: 10/31/2021] [Accepted: 10/31/2021] [Indexed: 12/28/2022] Open
Abstract
Small extracellular vesicles (sEV), which are released to body fluids (e.g., serum, urine) by all types of human cells, may stimulate or inhibit the innate and adaptive immune response through multiple mechanisms. Exosomes or sEV have on their surface many key receptors of immune response, including major histocompatibility complex (MHC) components, identical to their cellular origin. They also exhibit an ability to carry antigen and target leukocytes either via interaction with cell surface receptors or intracellular delivery of inflammatory mediators, receptors, enzymes, mRNAs, and noncoding RNAs. By the transfer of donor MHC antigens to recipient antigen presenting cells sEV may also contribute to T cell allorecognition and alloresponse. Here, we review the influence of sEV on the development of rejection or tolerance in the setting of solid organ and tissue allotransplantation. We also summarize and discuss potential applications of plasma and urinary sEV as biomarkers in the context of transplantation. We focus on the attempts to use sEV as a noninvasive approach to detecting allograft rejection. Preliminary studies show that both sEV total levels and a set of specific molecules included in their cargo may be an evidence of ongoing allograft rejection.
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Affiliation(s)
- Justyna E. Gołębiewska
- Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdańsk, 80-210 Gdańsk, Poland;
| | - Anna Wardowska
- Department of Physiopathology, Medical University of Gdańsk, 80-210 Gdańsk, Poland;
| | - Monika Pietrowska
- Centre for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie National Research Institute of Oncology, 44-102 Gliwice, Poland;
| | - Anna Wojakowska
- Institute of Bioorganic Chemistry Polish Academy of Sciences, 61-704 Poznań, Poland;
| | - Alicja Dębska-Ślizień
- Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdańsk, 80-210 Gdańsk, Poland;
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Chen J, Huang F, Hou Y, Lin X, Liang R, Hu X, Zhao J, Wang J, Olsen N, Zheng SG. TGF-β-induced CD4+ FoxP3+ regulatory T cell-derived extracellular vesicles modulate Notch1 signaling through miR-449a and prevent collagen-induced arthritis in a murine model. Cell Mol Immunol 2021; 18:2516-2529. [PMID: 34556822 PMCID: PMC8545930 DOI: 10.1038/s41423-021-00764-y] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Accepted: 08/21/2021] [Indexed: 02/08/2023] Open
Abstract
CD4+FOXP3+ Treg cells are central to the maintenance of self-tolerance and can be defective in autoimmunity. In autoimmune rheumatic diseases, dysfunctional self-tolerance, is to a large extent, caused by insufficient Treg-cell activity. Although nTregs have therapeutic effects in vivo, their relative scarcity and slow rate of in vitro expansion hinder the application of nTreg therapy. It was previously reported that EVs contribute significantly to the suppressive function of FOXP3+ Treg cells. Considering that the stability and plasticity of nTregs remain major challenges in vivo, we established EVs derived from in vitro TGF-β-induced Treg cells (iTreg-EVs) and assessed their functions in a murine model of autoimmune arthritis. The results demonstrated that iTreg-EVs preferentially homed to the pathological joint and efficiently prevented the imbalance in Th17/Treg cells in arthritic mice. Furthermore, we found that miR-449a-5p mediated Notch1 expression modulation and that miR-449a-5p knockdown abolished the effects of iTreg-EVs on effector T cells and regulatory T cells in vitro and in vivo. Taken together, our results show that iTreg-EVs control the inflammatory responses of recipient T cells through miR-449a-5p-dependent modulation of Notch1 and ameliorate the development and severity of arthritis, which may provide a potential cell-free strategy based on manipulating iTreg-EVs to prevent autoimmune arthritis.
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Affiliation(s)
- Jingrong Chen
- grid.412558.f0000 0004 1762 1794Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong China ,grid.412558.f0000 0004 1762 1794Department of Internal Medicine, Division of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong China
| | - Feng Huang
- grid.412558.f0000 0004 1762 1794Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong China
| | - Yuluan Hou
- grid.412558.f0000 0004 1762 1794Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong China
| | - Xiaorong Lin
- grid.412558.f0000 0004 1762 1794Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong China
| | - Rongzhen Liang
- grid.412558.f0000 0004 1762 1794Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong China
| | - Xiaojiang Hu
- grid.412558.f0000 0004 1762 1794Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong China
| | - Jun Zhao
- grid.412558.f0000 0004 1762 1794Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong China
| | - Julie Wang
- grid.412558.f0000 0004 1762 1794Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong China
| | - Nancy Olsen
- grid.29857.310000 0001 2097 4281Division of Rheumatology, Department of Medicine, Penn State University Hershey Medical Center, Hershey, PA USA
| | - Song Guo Zheng
- grid.412558.f0000 0004 1762 1794Department of Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong China
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Immunopathology of Chronic Hepatitis B Infection: Role of Innate and Adaptive Immune Response in Disease Progression. Int J Mol Sci 2021; 22:ijms22115497. [PMID: 34071064 PMCID: PMC8197097 DOI: 10.3390/ijms22115497] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 05/20/2021] [Accepted: 05/21/2021] [Indexed: 02/07/2023] Open
Abstract
More than 250 million people are living with chronic hepatitis B despite the availability of highly effective vaccines and oral antivirals. Although innate and adaptive immune cells play crucial roles in controlling hepatitis B virus (HBV) infection, they are also accountable for inflammation and subsequently cause liver pathologies. During the initial phase of HBV infection, innate immunity is triggered leading to antiviral cytokines production, followed by activation and intrahepatic recruitment of the adaptive immune system resulting in successful virus elimination. In chronic HBV infection, significant alterations in both innate and adaptive immunity including expansion of regulatory cells, overexpression of co-inhibitory receptors, presence of abundant inflammatory mediators, and modifications in immune cell derived exosome release and function occurs, which overpower antiviral response leading to persistent viral infection and subsequent immune pathologies associated with disease progression towards fibrosis, cirrhosis, and hepatocellular carcinoma. In this review, we discuss the current knowledge of innate and adaptive immune cells transformations that are associated with immunopathogenesis and disease outcome in CHB patients.
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Tavasolian F, Hosseini AZ, Rashidi M, Soudi S, Abdollahi E, Momtazi-Borojeni AA, Sathyapalan T, Sahebkar A. The Impact of Immune Cell-derived Exosomes on Immune Response Initiation and Immune System Function. Curr Pharm Des 2021; 27:197-205. [PMID: 33290196 DOI: 10.2174/1381612826666201207221819] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Accepted: 08/16/2020] [Indexed: 11/22/2022]
Abstract
Exosomes are small extracellular vesicles that pass genetic material between various cells to modulate or alter their biological function. The role of exosomes is to communicate with the target cell for cell-to-cell communication. Their inherent characteristics of exosomes, such as adhesion molecules, allow targeting specifically to the receiving cell. Exosomes are involved in cell to cell communication in the immune system including antigen presentation, natural killer cells (NK cells) and T cell activation/polarisation, immune suppression and various anti-inflammatory processes. In this review, we have described various functions of exosomes secreted by the immune cells in initiating, activating and modulating immune responses; and highlight the distinct roles of exosomal surface proteins and exosomal cargo. Potential applications of exosomes such as distribution vehicles for immunotherapy are also discussed.
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Affiliation(s)
- Fataneh Tavasolian
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Ahmad Z Hosseini
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mohsen Rashidi
- Department of Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Sara Soudi
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Elham Abdollahi
- Department of Medical Immunology and Allergy, Student Research Committee, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir A Momtazi-Borojeni
- Nanotechnology Research Center, Department of Medical Biotechnology, Student Research Committee, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Thozhukat Sathyapalan
- Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull HU3 2JZ, United Kingdom
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
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Abeysinghe P, Turner N, Morean Garcia I, Mosaad E, Peiris HN, Mitchell MD. The Role of Exosomal Epigenetic Modifiers in Cell Communication and Fertility of Dairy Cows. Int J Mol Sci 2020; 21:ijms21239106. [PMID: 33266010 PMCID: PMC7731370 DOI: 10.3390/ijms21239106] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 11/27/2020] [Accepted: 11/27/2020] [Indexed: 02/06/2023] Open
Abstract
Abnormal uterine function affects conception rate and embryo development, thereby leading to poor fertility and reproduction failure. Exosomes are a nanosized subclass of extracellular vesicles (EV) that have important functions as intercellular communicators. They contain and carry transferable bioactive substances including micro RNA (miRNA) for target cells. Elements of the cargo can provide epigenetic modifications of the recipient cells and may have crucial roles in mechanisms of reproduction. The dairy industry accounts for a substantial portion of the economy of many agricultural countries. Exosomes can enhance the expression of inflammatory mediators in the endometrium, which contribute to various inflammatory diseases in transition dairy cows. This results in reduced fertility which leads to reduced milk production and increased cow maintenance costs. Thus, gaining a clear knowledge of exosomal epigenetic modifiers is critical to improving the breeding success and profitability of dairy farms. This review provides a brief overview of how exosomal miRNA contributes to inflammatory diseases and hence to poor fertility, particularly in dairy cows.
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Xu Z, Zeng S, Gong Z, Yan Y. Exosome-based immunotherapy: a promising approach for cancer treatment. Mol Cancer 2020; 19:160. [PMID: 33183286 PMCID: PMC7661275 DOI: 10.1186/s12943-020-01278-3] [Citation(s) in RCA: 327] [Impact Index Per Article: 65.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 11/03/2020] [Indexed: 02/08/2023] Open
Abstract
In the era of the rapid development of cancer immunotherapy, there is a high level of interest in the application of cell-released small vesicles that stimulate the immune system. As cell-derived nanovesicles, exosomes show great promise in cancer immunotherapy because of their immunogenicity and molecular transfer function. The cargoes carried on exosomes have been recently identified with improved technological advances and play functional roles in the regulation of immune responses. In particular, exosomes derived from tumor cells and immune cells exhibit unique composition profiles that are directly involved in anticancer immunotherapy. More importantly, exosomes can deliver their cargoes to targeted cells and thus influence the phenotype and immune-regulation functions of targeted cells. Accumulating evidence over the last decade has further revealed that exosomes can participate in multiple cellular processes contributing to cancer development and therapeutic effects, showing the dual characteristics of promoting and suppressing cancer. The potential of exosomes in the field of cancer immunotherapy is huge, and exosomes may become the most effective cancer vaccines, as well as targeted antigen/drug carriers. Understanding how exosomes can be utilized in immune therapy is important for controlling cancer progression; additionally, exosomes have implications for diagnostics and the development of novel therapeutic strategies. This review discusses the role of exosomes in immunotherapy as carriers to stimulate an anti-cancer immune response and as predictive markers for immune activation; furthermore, it summarizes the mechanism and clinical application prospects of exosome-based immunotherapy in human cancer.
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Affiliation(s)
- Zhijie Xu
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Shuangshuang Zeng
- Department of Pharmacy, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China
| | - Zhicheng Gong
- Department of Pharmacy, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Yuanliang Yan
- Department of Pharmacy, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China.
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Moloudizargari M, Redegeld F, Asghari MH, Mosaffa N, Mortaz E. Long-chain polyunsaturated omega-3 fatty acids reduce multiple myeloma exosome-mediated suppression of NK cell cytotoxicity. ACTA ACUST UNITED AC 2020; 28:647-659. [PMID: 32974883 DOI: 10.1007/s40199-020-00372-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 09/11/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Despite the advances in the treatment of multiple myeloma (MM), complete remission is usually challenging. The interactions between tumor and host cells, in which exosomes (EXs) play critical roles, have been shown to be among the major deteriorative tumor-promoting factors herein. Therefore, any endeavor to beneficially target these EX-mediated interactions could be of high importance. OBJECTIVES a) To investigate the effects of myeloma EXs on natural killer (NK) cell functions. b) To check whether treatment of myeloma cells with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), two polyunsaturated omega-3 fatty acids with known anti-cancer effects, can modify myeloma EXs in terms of their effects on natural killer functions. METHODS L363 cells were treated with either EPA or DHA or left untreated and the released EXs (designated as E-EX, D-EX and C-EX, respectively) were used to treat NK cells for functional studies. RESULTS Myeloma EXs (C-EXs) significantly reduced NK cytotoxicity against K562 cells (P ≤ 0.05), while the cytotoxicity suppression was significantly lower (P ≤ 0.05) in the (E-EX)- and (D-EX)-treated NK cells compared to the (C-EX)-treated cells. The expression of the activating NK receptor NKG2D and NK degranulation, after treatment with the EXs, were both altered following the same pattern. However, C-EXs could increase IFN-γ production in NK cells (P < 0.01), which was not significantly affected by EPA/DHA treatment. This indicates a dual effect of myeloma EXs on NK cells functions. CONCLUSION Our observations showed that myeloma EXs have both suppressive and stimulatory effects on different NK functions. Treatment of myeloma cells with EPA/DHA can reduce the suppressive effects of myeloma EXs while maintaining their stimulatory effects. These findings, together with the previous findings on the anti-cancer effects of EPA/DHA, provide stronger evidence for the repositioning of the currently existing EPA/DHA supplements to be used in the treatment of MM as an adjuvant treatment. EXs released from L363 (myeloma) cells in their steady state increase IFN-γ production of NK cells, while reduce their cytotoxicity against the K562 cell line (right blue trace). EXs from L363 cells pre-treated with either EPA or DHA are weaker stimulators of IFN-γ production. These EXs also increase NK cytotoxicity and NKG2D expression (left brown trace) compared to the EXs obtained from untreated L363 cells. Based on these findings, myeloma EXs have both suppressive and stimulatory effects on different NK functions depending on the properties of their cells of origin, which can be exploited in the treatment of myeloma.
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Affiliation(s)
- Milad Moloudizargari
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Frank Redegeld
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands
| | - Mohammad Hossein Asghari
- Department of Pharmacology and Toxicology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Nariman Mosaffa
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Esmaeil Mortaz
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. .,Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands. .,Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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47
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Exosome: A New Player in Translational Nanomedicine. J Clin Med 2020; 9:jcm9082380. [PMID: 32722531 PMCID: PMC7463834 DOI: 10.3390/jcm9082380] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 07/20/2020] [Accepted: 07/22/2020] [Indexed: 02/07/2023] Open
Abstract
Summary: Exosomes are extracellular vesicles released by the vast majority of cell types both in vivo and ex vivo, upon the fusion of multivesicular bodies (MVBs) with the cellular plasma membrane. Two main functions have been attributed to exosomes: their capacity to transport proteins, lipids and nucleic acids between cells and organs, as well as their potential to act as natural intercellular communicators in normal biological processes and in pathologies. From a clinical perspective, the majority of applications use exosomes as biomarkers of disease. A new approach uses exosomes as biologically active carriers to provide a platform for the enhanced delivery of cargo in vivo. One of the major limitations in developing exosome-based therapies is the difficulty of producing sufficient amounts of safe and efficient exosomes. The identification of potential proteins involved in exosome biogenesis is expected to directly cause a deliberate increase in exosome production. In this review, we summarize the current state of knowledge regarding exosomes, with particular emphasis on their structural features, biosynthesis pathways, production techniques and potential clinical applications.
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48
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Resveratrol-primed exosomes strongly promote the recovery of motor function in SCI rats by activating autophagy and inhibiting apoptosis via the PI3K signaling pathway. Neurosci Lett 2020; 736:135262. [PMID: 32682847 DOI: 10.1016/j.neulet.2020.135262] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 06/24/2020] [Accepted: 07/15/2020] [Indexed: 12/14/2022]
Abstract
Spinal cord injury (SCI) is a traumatic condition of the central nervous system (CNS) that can cause paralysis of the limbs. The molecular mechanisms of neural repair following SCI remain unclear and no effective treatment for SCI currently exists, since drugs have difficulty crossing the blood-brain barrier (BBB). The present study aimed to investigate whether exosomes could be used as specific carriers of resveratrol for induction of neuronal autophagy both in vitro and in vivo for the treatment of SCI. The results indicate that exosomes are able to enhance the solubility of resveratrol and enhance penetration of the drug through the BBB, thereby increasing its concentration in the CNS. Exosomes derived from resveratrol-treated primary microglia (Exo + Res) assisted the rehabilitation of paralyzed limbs in rats. Restoration of neural function following SCI was mediated through increased induction of autophagy and inhibition of apoptosis of neurons both in vitro and in vivo via activation of the PI3K signaling pathway. The mechanism of action of Exo + Res may be associated with the PI3K inhibitor 3-methyladenine (3-MA) in primary spinal neurons. The results suggest that Exo + Res are highly effective at crossing the BBB with good stability, suggesting they have potential for enhancing targeted drug delivery and the recovery of neuronal function in SCI therapy, likely associated with the induction of autophagy and inhibition of apoptosis via the PI3K signaling pathway.
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49
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Integrin and PD-1 Ligand Expression on Circulating Extracellular Vesicles in Systemic Inflammatory Response Syndrome and Sepsis. Shock 2020; 52:13-22. [PMID: 30036273 DOI: 10.1097/shk.0000000000001228] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Extracellular vesicles (EVs) in the plasma mediate important intercellular communications in the pathogenesis of cancer and inflammatory diseases. EVs express integrins that regulate target specificities and programmed cell death ligand 1 and 2 (PD-L1 and 2) that suppress lymphocyte activation. However, the roles of these molecules on EVs in systemic inflammatory response syndrome (SIRS) and sepsis remain little understood. This study aimed to investigate how the EV expression of integrins and PD-1 ligands might differ in SIRS and sepsis, compared with healthy controls, and to correlate their expression with the clinical parameters reflecting pathogenesis. Twenty-seven SIRS patients without sepsis, 27 sepsis patients, and 18 healthy volunteers were included. EVs were isolated from plasma samples. The expression of three major integrins (β1, β2, β3 integrins) and PD-L1 and 2 were measured. The EV expression of β2 integrin and PD-L2 was significantly increased in sepsis patients compared with healthy controls. EV expression of PD-L1 was not elevated in sepsis and SIRS; however, circulating soluble PD-L1 levels were significantly higher in sepsis. Furthermore, EV expression of β2 integrin in sepsis patients correlated with hypotension and reduced kidney function. In addition, soluble PD-L1 levels correlated with sepsis severity, impaired kidney function, and impaired central nervous system function. These results suggest the potential involvements of the EV β2 integrin, as well as EV PD-L2 and soluble PD-L1, in the septic pathogenesis that occurs with the systemic immune activation leading to multiple organ dysfunctions.
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50
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Wang M, Yu F, Li P, Wang K. Emerging Function and Clinical Significance of Exosomal circRNAs in Cancer. MOLECULAR THERAPY. NUCLEIC ACIDS 2020; 21:367-383. [PMID: 32650235 PMCID: PMC7340966 DOI: 10.1016/j.omtn.2020.06.008] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 04/18/2020] [Accepted: 06/09/2020] [Indexed: 02/08/2023]
Abstract
Exosomes are a type of extracellular vesicles (EVs) secreted by almost all cells, with a diameter range of 30-150 nm and a lipid bilayer membrane. Exosomes are now considered as vital mediators of intercellular communication and participate in multiple cellular processes, such as signal transduction and antigen presentation. Recently, circular RNAs (circRNAs), a novel class of noncoding RNAs (ncRNAs), have been found to be abundant and stable in exosomes. Increasing evidence indicates that exosome-derived circRNAs act as signaling molecules to regulate cancer growth, angiogenesis, invasion, metastasis, and sensitivity to chemotherapy. Moreover, circulating exosomal circRNAs can reflect the progression and malignant characteristics of cancer, implying their great potential as promising, non-invasive biomarkers for cancer diagnosis and prognosis. In this review, we summarize the recent progress on the functional roles of exosomal circRNAs in cancer progression, discussing their potential as promising biomarkers and therapeutic targets in cancer. Comprehensive elucidation of molecular mechanisms relevant to the implications of exosomal circRNAs in cancer progression will be conducive to the development of innovative diagnostic and therapeutic approaches in cancer.
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Affiliation(s)
- Man Wang
- Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China.
| | - Fei Yu
- Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Peifeng Li
- Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Kun Wang
- Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China.
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