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Tiberti N, Castilletti C, Gobbi FG. Extracellular vesicles in arbovirus infections: from basic biology to potential clinical applications. Front Cell Infect Microbiol 2025; 15:1558520. [PMID: 40357393 PMCID: PMC12066795 DOI: 10.3389/fcimb.2025.1558520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Accepted: 04/04/2025] [Indexed: 05/15/2025] Open
Abstract
Arthropod-borne viruses, or arboviruses, are currently considered a global health threat responsible for potentially severe human diseases. The increased population density, changes in land use and climate change are some of the factors that are contributing to the spread of these infections over the last years. The pathogenesis of these diseases and the mechanisms of interaction with the host, especially those leading to the development of severe forms, are yet to be fully understood. In recent years extracellular vesicles (EVs) have emerged as important players in the inter-cellular and host-pathogen interaction arising a lot of interest also in the field of vector-borne viruses. In this context, EVs seem to play a dual role, by either promoting, thus facilitating, or preventing infection. Many studies are showing how viruses can hijack the vesiculation machinery to escape the host immune response and exploit EVs to sustain their replication and propagation, even though EVs shed by immune cells seem essential to promote antiviral responses. In this manuscript we reviewed the current knowledge regarding the association between EVs and vector-borne viruses, paying particular attention to their possible role in disease transmission and dissemination, as well as to their potential as novel tools for clinical applications, spanning from biomarkers of clinical utility to novel therapeutic options.
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Affiliation(s)
- Natalia Tiberti
- Department of Infectious, Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Verona, Italy
| | - Concetta Castilletti
- Department of Infectious, Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Verona, Italy
| | - Federico Giovanni Gobbi
- Department of Infectious, Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Verona, Italy
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
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Zhou T, Fang G, Wang Z, Qiao Z, Nie N, Fu B, Tseng PH, Sun X, Chen YC. Digital Lasing Biochip for Tumor-Derived Exosome Analysis. Anal Chem 2025; 97:5605-5611. [PMID: 40042136 PMCID: PMC11923948 DOI: 10.1021/acs.analchem.4c06172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 02/03/2025] [Accepted: 02/17/2025] [Indexed: 03/19/2025]
Abstract
Digital microfluidics represents an emerging versatile platform that offers numerous advantages in biomolecule detection. However, conventional probes often lack high-intensity and high-sensitivity signals, making it challenging for precise and automatic analysis. Recently, optical microresonators stand as a prominent high-sensitivity detection in the biological field. Here we introduce whispering gallery mode (WGM) microlasers into the microwell array, forming a digital lasing detection system. The lasing signal makes it highly sensitive, which amplifies the subtle changes via the strong interactions of light and matter. The microfluidic droplet technique further allowed microlasers with uniform laser thresholds and high-throughput fabrication. We utilized this tool for the analysis of exosomes derived from tumor spheroids. We believe that this digital optofluidic system could serve as a promising tool in diverse biomolecule assays and various biomedical applications.
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Affiliation(s)
- Tian Zhou
- School
of Electrical and Electronics Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
| | - Guocheng Fang
- School
of Electrical and Electronics Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
| | - Ziyihui Wang
- School
of Precision Instrument and Optoelectronics Engineering, Tianjin University, Tianjin 300072, China
| | - Zhen Qiao
- School
of Optical-Electrical and Computer Engineering, University of Shanghai for Science and Technology, No. 516 Jun Gong Road, Shanghai 200093, China
| | - Ningyuan Nie
- School
of Electrical and Electronics Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
| | - Bowen Fu
- School
of Electrical and Electronics Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
| | - Po-Hao Tseng
- School
of Electrical and Electronics Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
| | - Xiyu Sun
- School
of Electrical and Electronics Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
| | - Yu-Cheng Chen
- School
of Electrical and Electronics Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
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3
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Luan X, Wang X, Bian G, Li X, Gao Z, Liu Z, Zhang Z, Han T, Zhao J, Zhao H, Luan X, Zhu W, Dong L, Guo F. Exosome applications for the diagnosis and treatment of pancreatic ductal adenocarcinoma: An update (Review). Oncol Rep 2025; 53:13. [PMID: 39575479 PMCID: PMC11605277 DOI: 10.3892/or.2024.8846] [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: 08/08/2024] [Accepted: 10/30/2024] [Indexed: 11/28/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a malignant neoplasm that typically manifests with subtle clinical manifestations in its early stages and frequently eludes diagnosis until the advanced phases of the disease. The limited therapeutic options available for PDAC significantly contribute to its high mortality rate, highlighting the urgent need for novel biomarkers capable of effectively identifying early clinical manifestations and facilitating precise diagnosis. The pivotal role of cellular exosomes in both the pathogenesis and therapeutic interventions for PDAC has been underscored. Furthermore, researchers have acknowledged the potential of exosomes as targeted drug carriers against regulatory cells in treating PDAC. The present article aims to provide a comprehensive review encompassing recent advancements in utilizing exosomes for elucidating mechanisms underlying disease development, patterns of metastasis, diagnostic techniques and treatment strategies associated with PDAC.
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Affiliation(s)
- Xinchi Luan
- Pathophysiology Department, School of Basic Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China
| | - Xuezhe Wang
- Pathophysiology Department, School of Basic Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China
| | - Gang Bian
- Department of Gastroenterology, Affiliated Qingdao Third People's Hospital, Qingdao University, Qingdao, Shandong 266041, P.R. China
| | - Xiaoxuan Li
- Department of Oncology, Key Laboratory of Cancer Molecular and Translational Research, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266031, P.R. China
| | - Ziru Gao
- Pathophysiology Department, School of Basic Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China
| | - Zijiao Liu
- School of Clinical and Basic Medicine and Institute of Basic Medicine, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China
| | - Zhishang Zhang
- Pathophysiology Department, School of Basic Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China
| | - Tianyue Han
- Pathophysiology Department, School of Basic Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China
| | - Jinpeng Zhao
- Pathophysiology Department, School of Basic Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China
| | - Hongjiao Zhao
- Pathophysiology Department, School of Basic Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China
| | - Xinyue Luan
- Pathophysiology Department, School of Basic Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China
| | - Wuhui Zhu
- Department of Hepatobiliary surgery, Affiliated Qingdao Third People's Hospital, Qingdao University, Qingdao, Shandong 266041, P.R. China
| | - Lili Dong
- Department of Gastroenterology, Affiliated Qingdao Third People's Hospital, Qingdao University, Qingdao, Shandong 266041, P.R. China
| | - Feifei Guo
- Pathophysiology Department, School of Basic Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China
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4
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Sharma A, Bhatia D. Programmable bionanomaterials for revolutionizing cancer immunotherapy. Biomater Sci 2024; 12:5415-5432. [PMID: 39291418 DOI: 10.1039/d4bm00815d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Abstract
Cancer immunotherapy involves a cutting-edge method that utilizes the immune system to detect and eliminate cancer cells. It has shown substantial effectiveness in treating different types of cancer. As a result, its growing importance is due to its distinct benefits and potential for sustained recovery. However, the general deployment of this treatment is hindered by ongoing issues in maintaining minimal toxicity, high specificity, and prolonged effectiveness. Nanotechnology offers promising solutions to these challenges due to its notable attributes, including expansive precise surface areas, accurate ability to deliver drugs and controlled surface chemistry. This review explores the current advancements in the application of nanomaterials in cancer immunotherapy, focusing on three primary areas: monoclonal antibodies, therapeutic cancer vaccines, and adoptive cell treatment. In adoptive cell therapy, nanomaterials enhance the expansion and targeting capabilities of immune cells, such as T cells, thereby improving their ability to locate and destroy cancer cells. For therapeutic cancer vaccines, nanoparticles serve as delivery vehicles that protect antigens from degradation and enhance their uptake by antigen-presenting cells, boosting the immune response against cancer. Monoclonal antibodies benefit from nanotechnology through improved delivery mechanisms and reduced off-target effects, which increase their specificity and effectiveness. By highlighting the intersection of nanotechnology and immunotherapy, we aim to underscore the transformative potential of nanomaterials in enhancing the effectiveness and safety of cancer immunotherapies. Nanoparticles' ability to deliver drugs and biomolecules precisely to tumor sites reduces systemic toxicity and enhances therapeutic outcomes.
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Affiliation(s)
- Ayushi Sharma
- Department of Biotechnology, Institute of Applied Sciences and Humanities, GLA University, Mathura, Uttar Pradesh-281406, India.
| | - Dhiraj Bhatia
- Department of Biological Sciences and Engineering, Indian Institute of Technology Gandhinagar, Palaj 382355, Gandhinagar, India
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Wang Y, Ma H, Zhang X, Xiao X, Yang Z. The Increasing Diagnostic Role of Exosomes in Inflammatory Diseases to Leverage the Therapeutic Biomarkers. J Inflamm Res 2024; 17:5005-5024. [PMID: 39081872 PMCID: PMC11287202 DOI: 10.2147/jir.s475102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 07/11/2024] [Indexed: 08/02/2024] Open
Abstract
Inflammatory diseases provide substantial worldwide concerns, affecting millions of people and healthcare systems by causing ongoing discomfort, diminished quality of life, and increased expenses. In light of the progress made in treatments, the limited effectiveness and negative side effects of present pharmaceuticals need a more comprehensive comprehension of the underlying processes in order to develop more precise remedies. Exosomes, which are tiny vesicles that play a vital role in cell communication, have been identified as prospective vehicles for effective delivery of anti-inflammatory medicines, immunomodulators, and gene treatments. Vesicles, which are secreted by different cells, have a crucial function in communicating between cells. This makes them valuable in the fields of diagnostics and therapies, particularly for inflammatory conditions. Exosomes have a role in regulating the immune system, transporting cytokines, and influencing cell signaling pathways associated with inflammation. They consist of proteins, lipids, and genetic information that have an impact on immune responses and inflammation. Scientists are now investigating exosomes as biomarkers for inflammatory disease. This review article aims to develop non-invasive diagnostic techniques with improved sensitivity and specificity. Purpose of this review is a thorough examination of exosomes in pharmacology, specifically emphasizing their origin, contents, and functions, with the objective of enhancing diagnostic and therapeutic strategies for inflammatory conditions. Gaining a comprehensive understanding of the intricate mechanisms involved in exosome-mediated interactions and their impact on immune responses is of utmost importance in order to devise novel approaches for tackling inflammatory disease and enhancing patient care.
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Affiliation(s)
- Yan Wang
- Department of Clinical Laboratory, The Second Hospital of Jilin University, Changchun, 130000, People’s Republic of China
| | - Hui Ma
- Department of Clinical Laboratory, The Second Hospital of Jilin University, Changchun, 130000, People’s Republic of China
| | - Xiaohua Zhang
- Department of Clinical Laboratory, The Second Hospital of Jilin University, Changchun, 130000, People’s Republic of China
| | - Xia Xiao
- Department of Clinical Laboratory, The Second Hospital of Jilin University, Changchun, 130000, People’s Republic of China
| | - Zecheng Yang
- Department of Gastrointestinal Surgery, The Second Hospital of Jilin University, Changchun, 130000, People’s Republic of China
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Wang Z, Zhang Y, Li X. Mitigation of Oxidative Stress in Idiopathic Pulmonary Fibrosis Through Exosome-Mediated Therapies. Int J Nanomedicine 2024; 19:6161-6176. [PMID: 38911503 PMCID: PMC11193999 DOI: 10.2147/ijn.s453739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Accepted: 05/01/2024] [Indexed: 06/25/2024] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) poses a formidable clinical challenge, characterized by the thickening of alveolar septa and the onset of pulmonary fibrosis. The pronounced activation of oxidative stress emerges as a pivotal hallmark of inflammation. Traditional application of exogenous antioxidants proves inadequate in addressing oxidative stress, necessitating exploration into strategies to augment their antioxidant efficacy. Exosomes, nano-sized extracellular vesicles harboring a diverse array of bioactive factors, present as promising carriers with the potential to meet this challenge. Recent attention has been directed towards the clinical applications of exosomes in IPF, fueling the impetus for this comprehensive review. We have compiled fresh insights into the role of exosomes in modulating oxidative stress in IPF and delved into their potential as carriers for regulating endogenous reactive oxygen species generation. This review endeavors to bridge the divide between exosome research and IPF, traversing from bedside to bench. Through the synthesis of recent findings, we propose exosomes as a novel and promising strategy for improving the outcomes of IPF therapy.
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Affiliation(s)
- Zaiyan Wang
- Department of Pulmonary and Critical Care Medicine, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318, People’s Republic of China
| | - Yuan Zhang
- Department of Pulmonary and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People’s Republic of China
| | - Xiaoning Li
- Department of Geriatric Medicine, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318, People’s Republic of China
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7
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Pordanjani PM, Bolhassani A, Pouriayevali MH, Milani A, Rezaei F. Engineered dendritic cells-derived exosomes harboring HIV-1 Nef mut-Tat fusion protein and heat shock protein 70: A promising HIV-1 safe vaccine candidate. Int J Biol Macromol 2024; 270:132236. [PMID: 38768924 DOI: 10.1016/j.ijbiomac.2024.132236] [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: 03/23/2024] [Revised: 05/04/2024] [Accepted: 05/07/2024] [Indexed: 05/22/2024]
Abstract
Antigen presenting cells (APCs)-derived exosomes are nano-vesicles that can induce antigen-specific T cell responses, and possess therapeutic effects in clinical settings. Moreover, dendritic cells (DCs)-based vaccines have been developed to combat human immunodeficiency virus-1 (HIV-1) infection in preclinical and clinical trials. We investigated the immunostimulatory effects (B- and T-cells activities) of DCs- and exosomes-based vaccine constructs harboring HIV-1 Nefmut-Tat fusion protein as an antigen candidate and heat shock protein 70 (Hsp70) as an adjuvant in mice. The modified DCs and engineered exosomes harboring Nefmut-Tat protein or Hsp70 were prepared using lentiviral vectors compared to electroporation, characterized and evaluated by in vitro and in vivo immunological tests. Our data indicated that the engineered exosomes induced high levels of total IgG, IgG2a, IFN-γ, TNF-α and Granzyme B. Moreover, co-injection of exosomes harboring Hsp70 could significantly increase the secretion of antibodies, cytokines and Granzyme B. The highest levels of IFN-γ and TNF-α were observed in exosomes harboring Nefmut-Tat combined with exosomes harboring Hsp70 (Exo-Nefmut-Tat + Exo-Hsp70) regimen after single-cycle replicable (SCR) HIV-1 exposure. Generally, Exo-Nefmut-Tat + Exo-Hsp70 regimen can be considered as a promising safe vaccine candidate due to high T-cells (Th1 and CTL) activity and its maintenance against SCR HIV-1 exposure.
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Affiliation(s)
| | - Azam Bolhassani
- Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
| | - Mohammad Hassan Pouriayevali
- Department of Arboviruses and Viral Hemorrhagic Fevers (National Reference Laboratory), Pasteur Institute of Iran, Tehran, Iran
| | - Alireza Milani
- Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran; Iranian Comprehensive Hemophilia Care Center, Tehran, Iran
| | - Fatemeh Rezaei
- Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran
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8
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Huang X, Tan Y, Wu R, Li Q, Luo S. MicroRNA-98-5p Inhibits IFI44L-Mediated Differentiation of Dendritic Cells and Activation of Interferon Pathway in Systemic Lupus Erythematosus. Immunol Invest 2024; 53:475-489. [PMID: 38198612 DOI: 10.1080/08820139.2023.2300346] [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: 01/12/2024]
Abstract
MicroRNA-98-5p (miR-98-5p) plays a protective role in the pathogenesis of autoimmune diseases through anti-inflammatory effects, but little is known about its role in Systemic lupus erythematosus (SLE). Our previous study suggested Interferon-inducible 44 like (IFI44L) overexpressed in monocytes which contributes to the pathogenesis of SLE by enhancing the maturation and functions of monocyte-derived dendritic cells (Mo-DCs), and miR-98-5p can regulate the expression of IFI44L. In this study, we identified miR-98-5p lowly expressed in both peripheral blood mononuclear cells (PBMCs) and monocytes of SLE patients along with high expression of IFI44L. IFI44L serves as target gene of miR-98-5p which inhibits differentiation of Mo-DCs and IFI44L-mediated activation of interferon pathway. We further showed that miR-98-5p promotes methylation of the IFI44L promoter to down-regulate its expression in SLE. Our results reveal an important role for miR-98-5p in the IFI44L-mediated immune imbalance of SLE and suggest a potential therapeutic target for SLE in the future.
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Affiliation(s)
- Xin Huang
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Yixin Tan
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Ruifang Wu
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Qianwen Li
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Shuaihantian Luo
- Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, China
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9
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Li T, Chen X, Qi Q, Feng X. Bovine Milk Derived Exosomes Affect Gut Microbiota of DSS-Induced Colitis Mice. Indian J Microbiol 2024; 64:100-109. [PMID: 38468747 PMCID: PMC10924850 DOI: 10.1007/s12088-023-01131-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Accepted: 10/27/2023] [Indexed: 03/13/2024] Open
Abstract
The objective of this study was to investigate the effect of bovine milk derived exosomes (MDEs) on the gut microbiota of Dextran sodium sulfate (DSS)-induced colitis mice. Total of 42 specific pathogen free (SPF) male BALB/c mice (3 weeks old) were randomly assigned to three groups including control group, DSS group (DSS) and bovine milk derived exosome group (Exo), with 7 replicates/cages per treatment and two mice in one cage. 16S rRNA gene sequencing of cecal digesta samples was conducted. DSS significantly decreased the average daily feed intake of mice in DSS and Exo groups (P = 0.03). Shannon index of the DSS group was significantly lower than the control group (P < 0.05) whereas no difference between the control group and Exo group was observed. Administration of MDEs tended to increase the relative abundance of Campylobaterota. Compared to the control group, the relative abundance of Roseburia was significantly decreased in the DSS group (P < 0.05) whereas no difference between the Exo group and control group was observed. MDEs also tended to increase the relative abundance of Lachnospiraceae_UCG_006. In conclusion, oral administration of 10 µL MDEs (1 mg/mL) positively affected gut microbiota of DSS-induced colitis mice. The results of this study provided valuable reference for MDEs application in the prevention and treatment of colitis.
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Affiliation(s)
- Tonghao Li
- School of Life Science and Engineering, Foshan University, No. 33 Guangyun Road, Nanhai District, Foshan, Guangdong China
| | - Xiaolin Chen
- School of Life Science and Engineering, Foshan University, No. 33 Guangyun Road, Nanhai District, Foshan, Guangdong China
| | - Qien Qi
- School of Life Science and Engineering, Foshan University, No. 33 Guangyun Road, Nanhai District, Foshan, Guangdong China
| | - Xin Feng
- School of Life Science and Engineering, Foshan University, No. 33 Guangyun Road, Nanhai District, Foshan, Guangdong China
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10
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Wang Z, Wang Q, Qin F, Chen J. Exosomes: a promising avenue for cancer diagnosis beyond treatment. Front Cell Dev Biol 2024; 12:1344705. [PMID: 38419843 PMCID: PMC10900531 DOI: 10.3389/fcell.2024.1344705] [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: 11/26/2023] [Accepted: 01/31/2024] [Indexed: 03/02/2024] Open
Abstract
Exosomes, extracellular vesicles secreted by cells, have garnered significant attention in recent years for their remarkable therapeutic potential. These nanoscale carriers can be harnessed for the targeted delivery of therapeutic agents, such as pharmaceuticals, proteins, and nucleic acids, across biological barriers. This versatile attribute of exosomes is a promising modality for precision medicine applications, notably in the realm of cancer therapy. However, despite their substantial therapeutic potential, exosomes still confront challenges tied to standardization and scalability that impede their practice in clinical applications. Moreover, heterogeneity in isolation methodologies and limited cargo loading mechanisms pose obstacles to ensuring consistent outcomes, thereby constraining their therapeutic utility. In contrast, exosomes exhibit a distinct advantage in cancer diagnosis, as they harbor specific signatures reflective of the tumor's genetic and proteomic profile. This characteristic endows them with the potential to serve as valuable liquid biopsies for non-invasive and real-time monitoring, making possible early cancer detection for the development of personalized treatment strategies. In this review, we provide an extensive evaluation of the advancements in exosome research, critically examining their advantages and limitations in the context of cancer therapy and early diagnosis. Furthermore, we present a curated overview of the most recent technological innovations utilizing exosomes, with a focus on enhancing the efficacy of early cancer detection.
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Affiliation(s)
- Zhu Wang
- Breast Center, West China Hospital, Sichuan University, Chengdu, China
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Institute for Breast Health Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Qianqian Wang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Feng Qin
- School of Basic Medicine, Dali University, Dali, Yunnan, China
| | - Jie Chen
- Breast Center, West China Hospital, Sichuan University, Chengdu, China
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Institute for Breast Health Medicine, West China Hospital, Sichuan University, Chengdu, China
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11
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Tendulkar R, Tendulkar M. Current Update of Research on Exosomes in Cancer. Curr Mol Med 2024; 24:26-39. [PMID: 37461337 DOI: 10.2174/1566524023666230717105000] [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: 12/13/2022] [Revised: 04/12/2023] [Accepted: 05/25/2023] [Indexed: 08/01/2023]
Abstract
Exosomes are vesicles secreted by the plasma membrane of the cells delimited by a lipid bilayer membrane into the extracellular space of the cell. Their release is associated with the disposal mechanism to remove unwanted materials from the cells. Exosomes released from primary tumour sites migrate to other parts of the body to create a metastatic environment for spreading the tumour cells. We have reviewed that exosomes interfere with the tumour progression by (i) promoting angiogenesis, (ii) initiating metastasis, (iii) regulating tumour microenvironment (TME) and inflammation, (iv) modifying energy metabolism, and (v) transferring mutations. We have found that EVs play an important role in inducing tumour drug resistance against anticancer drugs. This review discusses the potential of exosomes to generate a significant therapeutic effect along with improved diagnosis, prognosis, insights on the various research conducted and their significant findings of our interest.
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Affiliation(s)
- Reshma Tendulkar
- Pharmaceutical Chemistry, Vivekanand Education Society's College of Pharmacy, India
| | - Mugdha Tendulkar
- Faculty of Science, Sardar Vallabhbhai College of Science, India
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12
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Zhang X, Wang J, Liu N, Wu W, Li H, Lu W, Guo X. Umbilical Cord Blood-Derived M1 Macrophage Exosomes Loaded with Cisplatin Target Ovarian Cancer In Vivo and Reverse Cisplatin Resistance. Mol Pharm 2023; 20:5440-5453. [PMID: 37819754 DOI: 10.1021/acs.molpharmaceut.3c00132] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/13/2023]
Abstract
We investigated the therapeutic efficacy of umbilical cord blood (UCB)-derived M1 macrophage exosomes loaded with cisplatin (CIS) in ovarian cancer and platinum resistance. M1 macrophages were purified by using CD14 magnetic beads and characterized by flow cytometry. Our analyses included morphology, particle size, particle concentration, potential, drug loading capacity, counts of entry into cells, antitumor effect in vivo, and the ability to reverse drug resistance. A2780, SKOV3, and A2780/DDP, SKOV3/DDP ovarian cancer cells (CIS-sensitive and CIS-resistant cell lines, respectively) were treated with CIS or CIS-loaded M1 macrophage exosomes (M1exoCISs). The encapsulation efficiency of CIS loading into M1 macrophage exosomes was approximately 30%. In vitro, M1exoCIS treatment reduced the CIS IC50 values of both A2780, SKOV3, and A2780/DDP, SKOV3/DDP cells. We evaluated the effect of M1exoCIS on tumor growth using a mouse ovarian cancer subcutaneous transplantation tumor model inoculated with A2780/DDP cells. M1exoCIS was observed in the liver, spleen, and tumor sites 24 h posttreatment; the fluorescence intensity of M1exoCIS is higher than that of CIS. After 7 days, M1exoCIS significantly inhibited the growth of subcutaneously transplanted tumors compared with CIS alone and had a longer survival time. Moreover, the toxicity test shows that M1exoCIS has less hepatorenal toxicity than CIS. To investigate the mechanism of M1exoCIS targeting, homing, and reversing drug resistance, we performed RT-PCR, Western blotting, and Proteome Profiler Human Receptor Array analyses. We found that A2780 and A2780/DDP cells expressed the integrin β1/CD29 receptor, while M1 exosomes expressed integrin β1/CD29. In addition, M1exos carries long noncoding RNA H19, implicated in PTEN protein upregulation and miR-130a and Pgp gene downregulation, leading to the reversal of CIS drug resistance. Therefore, UCB-derived M1exoCIS target tumor sites of ovarian cancer in vivo and can be used to increase the CIS sensitivity and cytotoxicity.
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Affiliation(s)
- Xiaohui Zhang
- Shanghai First Maternity and Infant Hospital, Tong Ji University School of Medicine, Shanghai 201204, China
| | - Jiapo Wang
- Shanghai First Maternity and Infant Hospital, Tong Ji University School of Medicine, Shanghai 201204, China
| | - Na Liu
- Shanghai First Maternity and Infant Hospital, Tong Ji University School of Medicine, Shanghai 201204, China
| | - Weimin Wu
- Shanghai First Maternity and Infant Hospital, Tong Ji University School of Medicine, Shanghai 201204, China
| | - Hong Li
- Shanghai Institute of Biochemistry and Cell Biology, Shanghai 200031, China
| | - Wen Lu
- Shanghai First Maternity and Infant Hospital, Tong Ji University School of Medicine, Shanghai 201204, China
| | - Xiaoqing Guo
- Shanghai First Maternity and Infant Hospital, Tong Ji University School of Medicine, Shanghai 201204, China
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13
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Wang J, Tan M, Wang Y, Liu X, Lin A. Advances in modification and delivery of nucleic acid drugs. Zhejiang Da Xue Xue Bao Yi Xue Ban 2023; 52:417-428. [PMID: 37643976 PMCID: PMC10495244 DOI: 10.3724/zdxbyxb-2023-0130] [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: 03/17/2023] [Accepted: 06/14/2023] [Indexed: 08/18/2023]
Abstract
Nucleic acid-based drugs, such as RNA and DNA drugs, exert their effects at the genetic level. Currently, widely utilized nucleic acid-based drugs include nucleic acid aptamers, antisense oligonucleotides, mRNA, miRNA, siRNA and saRNA. However, these drugs frequently encounter challenges during clinical application, such as poor stability, weak targeting specificity, and difficulties in traversing physiological barriers. By employing chemical modifications of nucleic acid structures, it is possible to enhance the stability and targeting specificity of certain nucleic acid drugs within the body, thereby improving delivery efficiency and reducing immunogenicity. Moreover, utilizing nucleic acid drug carriers can facilitate the transportation of drugs to lesion sites, thereby aiding efficient intracellular escape and promoting drug efficacy within the body. Currently, commonly employed delivery carriers include virus vectors, lipid nanoparticles, polymer nanoparticles, inorganic nanoparticles, protein carriers and extracellular vesicles. Nevertheless, individual modifications or delivery carriers alone are insufficient to overcome numerous obstacles. The integration of nucleic acid chemical modifications with drug delivery systems holds promise for achieving enhanced therapeutic effects. However, this approach also presents increased technical complexity and clinical translation costs. Therefore, the development of nucleic acid drug carriers and nucleic acid chemical modifications that are both practical and simple, while maintaining high efficacy, low toxicity, and precise nucleic acid delivery, has become a prominent research focus in the field of nucleic acid drug development. This review comprehensively summarizes the advancements in nucleic acid-based drug modifica-tions and delivery systems. Additionally, strategies to enhance nucleic acid drug delivery efficiency are discussed, with the aim of providing valuable insights for the translational application of nucleic acid drugs.
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Affiliation(s)
- Junfeng Wang
- College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
- Zhejiang University Cancer Center, Hangzhou 310058, China.
| | - Manman Tan
- College of Life Sciences, Zhejiang University, Hangzhou 310058, China
- Zhejiang University Cancer Center, Hangzhou 310058, China
| | - Ying Wang
- College of Life Sciences, Zhejiang University, Hangzhou 310058, China
- Zhejiang University Cancer Center, Hangzhou 310058, China
| | - Xiangrui Liu
- Zhejiang University Cancer Center, Hangzhou 310058, China.
| | - Aifu Lin
- College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
- Zhejiang University Cancer Center, Hangzhou 310058, China.
- The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Center for RNA Medicine, International Institutes of Medicine, Zhejiang University, Jinhua 322000, Zhejiang Province, China.
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14
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Kaur S, Nathani A, Singh M. Exosomal delivery of cannabinoids against cancer. Cancer Lett 2023; 566:216243. [PMID: 37257632 PMCID: PMC10426019 DOI: 10.1016/j.canlet.2023.216243] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 05/11/2023] [Accepted: 05/21/2023] [Indexed: 06/02/2023]
Abstract
Exosomes are extracellular vesicles (EVs) originating from endosomes that play a role in cellular communication. These vesicles which mimic the parental cells that release them are promising candidates for targeted drug delivery and therapeutic applications against cancer because of their favorable biocompatibility, specific targeting, low toxicity, and immunogenicity. Currently, Delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD) and other cannabinoids (e.g., CBG, THCV, CBC), are being explored for their anticancer and anti-proliferative properties. Several mechanisms, including cell cycle arrest, proliferation inhibition, activation of autophagy and apoptosis, inhibition of adhesion, metastasis, and angiogenesis have been proposed for their anticancer activity. EVs could be engineered as cannabinoid delivery systems for tumor-specificity leading to superior anticancer effects. This review discusses current techniques for EV isolation from various sources, characterization and strategies to load them with cannabinoids. More extensively, we culminate information available on different sources of EVs that have anticancer activity, mechanism of action of cannabinoids against various wild type and resistant tumors and role of CBD in histone modifications and cancer epigenetics. We have also enumerated the role of EVs containing cannabinoids against various tumors and in chemotherapy induced neuropathic pain.
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Affiliation(s)
- Sukhmandeep Kaur
- College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, 32307, USA
| | - Aakash Nathani
- College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, 32307, USA
| | - Mandip Singh
- College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, 32307, USA.
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15
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Systematic Identification and Comparison of the Expressed Profiles of Exosomal MiRNAs in Pigs Infected with NADC30-like PRRSV Strain. Animals (Basel) 2023; 13:ani13050876. [PMID: 36899733 PMCID: PMC10000162 DOI: 10.3390/ani13050876] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 02/16/2023] [Accepted: 02/22/2023] [Indexed: 03/04/2023] Open
Abstract
Exosomes are biological vesicles secreted and released by cells that act as mediators of intercellular communication and play a unique role in virus infection, antigen presentation, and suppression/promotion of body immunity. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most damaging pathogens in the pig industry and can cause reproductive disorders in sows, respiratory diseases in pigs, reduced growth performance, and other diseases leading to pig mortality. In this study, we used the PRRSV NADC30-like CHsx1401 strain to artificially infect 42-day-old pigs and isolate serum exosomes. Based on high-throughput sequencing technology, 305 miRNAs were identified in serum exosomes before and after infection, among which 33 miRNAs were significantly differentially expressed between groups (13 relatively upregulated and 20 relatively downregulated). Sequence conservation analysis of the CHsx1401 genome identified 8 conserved regions, of which a total of 16 differentially expressed (DE) miRNAs were predicted to bind to the conserved region closest to the 3' UTR of the CHsx1401 genome, including 5 DE miRNAs capable of binding to the CHsx1401 3' UTR (ssc-miR-34c, ssc-miR-375, ssc-miR-378, ssc-miR-486, ssc-miR-6529). Further analysis revealed that the target genes of differentially expressed miRNAs were widely involved in exosomal function-related and innate immunity-related signaling pathways, and 18 DE miRNAs (ssc-miR-4331-3p, ssc-miR-744, ssc-miR-320, ssc-miR-10b, ssc-miR-124a, ssc-miR-128, etc.) associated with PRRSV infection and immunity were screened as potential functional molecules involved in the regulation of PRRSV virus infection by exosomes.
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16
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Littig JPB, Moellmer R, Agrawal DK, Rai V. Future applications of exosomes delivering resolvins and cytokines in facilitating diabetic foot ulcer healing. World J Diabetes 2023; 14:35-47. [PMID: 36684384 PMCID: PMC9850797 DOI: 10.4239/wjd.v14.i1.35] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 11/22/2022] [Accepted: 12/21/2022] [Indexed: 01/10/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) increases the risk of many lethal and debilitating conditions. Among them, foot ulceration due to neuropathy, vascular disease, or trauma affects the quality of life of millions in the United States and around the world. Physiological wound healing is stalled in the inflammatory phase by the chronicity of inflammation without proceeding to the resolution phase. Despite advanced treatment, diabetic foot ulcers (DFUs) are associated with a risk of amputation. Thus, there is a need for novel therapies to address chronic inflammation, decreased angiogenesis, and impaired granulation tissue formation contributing to the non-healing of DFUs. Studies have shown promising results with resolvins (Rv) and anti-inflammatory therapies that resolve inflammation and enhance tissue healing. But many of these studies have encountered difficulty in the delivery of Rv in terms of efficiency, tissue targetability, and immunogenicity. This review summarized the perspective of optimizing the therapeutic application of Rv and cytokines by pairing them with exosomes as a novel strategy for targeted tissue delivery to treat non-healing chronic DFUs. The articles discussing the T2DM disease state, current research on Rv for treating inflammation, the role of Rv in enhancing wound healing, and exosomes as a delivery vehicle were critically reviewed to find support for the proposition of using Rv and exosomes in combination for DFUs therapy. The literature reviewed suggests the beneficial role of Rv and exosomes and exosomes loaded with anti-inflammatory agents as promising therapeutic agents in ulcer healing.
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Affiliation(s)
- Joshua P B Littig
- Translational Research, Western University of Health Sciences, Pomona, CA 91766, United States
| | - Rebecca Moellmer
- College of Podiatry, Western University of Health Sciences, Pomona, CA 91766, United States
| | - Devendra K Agrawal
- Translational Research, Western University of Health Sciences, Pomona, CA 91766, United States
| | - Vikrant Rai
- Translational Research, Western University of Health Sciences, Pomona, CA 91766, United States
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17
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Mitra T, Gulati R, Uppal A, Kumari SR, Tripathy S, Ranjan P, Janardhanan R. Prospecting of exosomal-miRNA signatures as prognostic marker for gestational diabetes mellitus and other adverse pregnancy outcomes. Front Endocrinol (Lausanne) 2023; 14:1097337. [PMID: 36843574 PMCID: PMC9946972 DOI: 10.3389/fendo.2023.1097337] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Accepted: 01/23/2023] [Indexed: 02/11/2023] Open
Abstract
Exosomal microRNA (ExomiRs) serves as potential cargo molecules responsible for post-translation of gene expression and intracellular communication playing a vital role in acting as clinically relevant prognostic biomarkers for identifying pregnancy-associated complications in patients. ExomiRs are associated with Gestational Diabetes Mellitus (GDM) as potential targets for understanding the pathophysiology of beta-cell dysfunction. ExomiRs (ExomiR 122, ExomiR 16-5p, ExomiR 215-5p, ExomiR 450b-3p, ExomiR 122-5p) aid to act as biomarkers and regulate the progression of diabetes and its related complication. These ExomiRshave been reported to interfere with the regulation of various genes such as ZEB2, IRS1, IRS2, GLUT1, GLUT4, etc. and inhibition of several pathways like PI3K/AKT, Wnt, and mTOR signaling pathways leading to the modulation in the development of GDM affecting the clinical and pathological features of women. These ExomiRs have also been associated with other pregnancy-associated complications, including preeclampsia, hypothyroidism, pregnancy loss, and ectopic pregnancies. On the other hand, overexpression of certain ExomiRs such as Exomir-515-5p, ExomiR-221, and ExomiR-96 serve a regulatory role in overcoming insulin resistance. Taken together, the current review focuses on the prospective capabilities of ExomiRs for diagnosis and clinical prognosis of GDM women with respect to pregnancy outcomes.
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Affiliation(s)
- Tridip Mitra
- Department of Medical Research, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | - Richa Gulati
- Department of Medical Research, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | | | - Sajeetha R Kumari
- Department of Obstetrics and Gynaecology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
| | | | - Priya Ranjan
- Department of Electrical Engineering, Biju Patnaik University of Technology, Rourkela, Odisha, India
| | - Rajiv Janardhanan
- Department of Medical Research, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
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18
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Harvey B, Fu X, Li L, Neupane KR, Anand N, Kolesar JM, Richards CI. Dendritic Cell Membrane-Derived Nanovesicles for Targeted T Cell Activation. ACS OMEGA 2022; 7:46222-46233. [PMID: 36570199 PMCID: PMC9773342 DOI: 10.1021/acsomega.2c04420] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 11/14/2022] [Indexed: 06/17/2023]
Abstract
T cells play an integral role in the generation of an effective immune response and are responsible for clearing foreign microbes that have bypassed innate immune system defenses and possess cognate antigens. The immune response can be directed toward a desired target through the selective priming and activation of T cells. Due to their ability to activate a T cell response, dendritic cells and endogenous vesicles from dendritic cells are being developed for cancer immunotherapy treatment. However, current platforms, such as exosomes and synthetic nanoparticles, are limited by their production methods and application constraints. Here, we engineer nanovesicles derived from dendritic cell membranes with similar properties as dendritic cell exosomes via nitrogen cavitation. These cell-derived nanovesicles are capable of activating antigen-specific T cells through direct and indirect mechanisms. Additionally, these nanovesicles can be produced in large yields, overcoming production constraints that limit clinical application of alternative immunomodulatory vesicle or nanoparticle-based methods. Thus, dendritic cell-derived nanovesicles generated by nitrogen cavitation show potential as an immunotherapy platform to stimulate and direct T cell response.
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Affiliation(s)
- Brock
T. Harvey
- Department
of Chemistry, College of Arts and Sciences, University of Kentucky, Lexington, Kentucky 40506, United States
| | - Xu Fu
- Light
Microscopy Facility, University of Kentucky, Lexington, Kentucky 40506, United States
| | - Lan Li
- Department
of Chemistry, College of Arts and Sciences, University of Kentucky, Lexington, Kentucky 40506, United States
| | - Khaga R. Neupane
- Department
of Chemistry, College of Arts and Sciences, University of Kentucky, Lexington, Kentucky 40506, United States
| | - Namrata Anand
- Department
of Pharmacy and Practice, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40506, United States
| | - Jill M. Kolesar
- Department
of Pharmacy and Practice, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40506, United States
| | - Christopher I. Richards
- Department
of Chemistry, College of Arts and Sciences, University of Kentucky, Lexington, Kentucky 40506, United States
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19
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Joseph J, Rahmani B, Cole Y, Puttagunta N, Lin E, Khan ZK, Jain P. Can Soluble Immune Checkpoint Molecules on Exosomes Mediate Inflammation? J Neuroimmune Pharmacol 2022; 17:381-397. [PMID: 34697721 PMCID: PMC10128092 DOI: 10.1007/s11481-021-10018-3] [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: 05/04/2021] [Accepted: 08/25/2021] [Indexed: 01/13/2023]
Abstract
Immune checkpoints (ICPs) are major co-signaling pathways that trigger effector functions in immune cells, with isoforms that are either membrane bound, engaging in direct cell to cell activation locally, or soluble, acting at distant sites by circulating freely or potentially via extracellular vesicles (EVs). Exosomes are small EVs secreted by a variety of cells carrying various proteins and nucleic acids. They are distributed extensively through biological fluids and have major impacts on infectious diseases, cancer, and neuroinflammation. Similarly, ICPs play key roles in a variety of disease conditions and have been extensively utilized as a prognostic tool for various cancers. Herein, we explored if the association between exosomes and ICPs could be a significant contributor of inflammation, particularly in the setting of cancer, neuroinflammation and viral infections, wherein the up regulation in both exosomal proteins and ICPs correlate with immunosuppressive effects. The detailed literature review of existing data highlights the significance and complexity of these two important pathways in mediating cancer and potentiating neuroinflammation via modulating overall immune response. Cells increasingly secret exosomes in response to intracellular signals from invading pathogens or cancerous transformations. These exosomes can carry a variety of cargo including proteins, nucleic acids, cytokines, and receptors/ligands that have functional consequences on recipient cells. Illustration generated using BioRender software.
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Affiliation(s)
- Julie Joseph
- Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 West Queen Lane, Philadelphia, PA, 19129, USA
| | - Benjamin Rahmani
- Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 West Queen Lane, Philadelphia, PA, 19129, USA
| | - Yonesha Cole
- Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 West Queen Lane, Philadelphia, PA, 19129, USA
| | - Neha Puttagunta
- Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 West Queen Lane, Philadelphia, PA, 19129, USA
| | - Edward Lin
- Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 West Queen Lane, Philadelphia, PA, 19129, USA
| | - Zafar K Khan
- Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 West Queen Lane, Philadelphia, PA, 19129, USA
| | - Pooja Jain
- Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 West Queen Lane, Philadelphia, PA, 19129, USA. .,Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 West Queen Lane, Philadelphia, PA, 19129, USA.
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20
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Harnessing the Therapeutic Potential of Exosomes: A Novel Strategy for Anticancer and Antiviral Therapy. BIOMED RESEARCH INTERNATIONAL 2022; 2022:3356467. [PMID: 36132081 PMCID: PMC9484893 DOI: 10.1155/2022/3356467] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 08/20/2022] [Accepted: 08/27/2022] [Indexed: 11/23/2022]
Abstract
Exosomes are extracellular membrane bound vesicles released from almost all cell types and can be retrieved from all body fluids. The molecular constituents of these extracellular bodies vary depending on their cell of origin, from which they can transport molecules such as DNA, RNA, proteins lipids, and several metabolites. They have been shown to execute several functions such as in cell growth, migration, differentiation, neuronal signaling, immune cell modulation, and some diseases such as cancer through intercellular communication and signaling. They are also described to act as key players in viral persistence and dissemination. Due to their ability to elicit potent cellular responses, high level of tolerance in host cells, and high efficiency in penetrating other cells, they are proposed to be potential therapeutics as well as vehicles for drug delivery. In recent years, several studies have been conducted in quest for the development of an effective anticancer therapy or antiviral therapy against highly persistent viruses. However, most of these studies become halted due to failure to achieve desired therapeutic outcomes. Nevertheless, the in vitro/in vivo application of exosomes in tumor and infectious disease diagnosis and therapy is prospective. This review discusses the role of exosomes as predictive markers for immune activation and potential targets for anticancer/antiviral therapies.
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21
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Zhang Y, Liu Q, Zhang X, Huang H, Tang S, Chai Y, Xu Z, Li M, Chen X, Liu J, Yang C. Recent advances in exosome-mediated nucleic acid delivery for cancer therapy. J Nanobiotechnology 2022; 20:279. [PMID: 35701788 PMCID: PMC9194774 DOI: 10.1186/s12951-022-01472-z] [Citation(s) in RCA: 165] [Impact Index Per Article: 55.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 05/19/2022] [Indexed: 02/07/2023] Open
Abstract
Cancer is a leading public health problem worldwide. Its treatment remains a daunting challenge, although significant progress has been made in existing treatments in recent years. A large concern is the poor therapeutic effect due to lack of specificity and low bioavailability. Gene therapy has recently emerged as a powerful tool for cancer therapy. However, delivery methods limit its therapeutic effects. Exosomes, a subset of extracellular vesicles secreted by most cells, have the characteristics of good biocompatibility, low toxicity and immunogenicity, and great designability. In the past decades, as therapeutic carriers and diagnostic markers, they have caught extensive attention. This review introduced the characteristics of exosomes, and focused on their applications as delivery carriers in DNA, messenger RNA (mRNA), microRNA (miRNA), small interfering RNA (siRNA), circular RNA (circRNA) and other nucleic acids. Meanwhile, their application in cancer therapy and exosome-based clinical trials were presented and discussed. Through systematic summarization and analysis, the recent advances and current challenges of exosome-mediated nucleic acid delivery for cancer therapy are introduced, which will provide a theoretical basis for the development of nucleic acid drugs.
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Affiliation(s)
- Ying Zhang
- Central Laboratory of Longgang District People's Hospital of Shenzhen & The Second Affiliated Hospital, The Chinese University of Hong Kong, Shenzhen, 518172, China
- Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, China
| | - Qiqi Liu
- Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, China
| | - Xinmeng Zhang
- Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, China
| | - Haoqiang Huang
- Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, China
| | - Shiqi Tang
- Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, China
| | - Yujuan Chai
- Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, China
| | - Zhourui Xu
- Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, China
| | - Meirong Li
- Central Laboratory of Longgang District People's Hospital of Shenzhen & The Second Affiliated Hospital, The Chinese University of Hong Kong, Shenzhen, 518172, China
- Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, China
| | - Xin Chen
- Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, China
| | - Jia Liu
- Central Laboratory of Longgang District People's Hospital of Shenzhen & The Second Affiliated Hospital, The Chinese University of Hong Kong, Shenzhen, 518172, China.
| | - Chengbin Yang
- Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, China.
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22
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Matsuzaka Y, Yashiro R. Immune Modulation Using Extracellular Vesicles Encapsulated with MicroRNAs as Novel Drug Delivery Systems. Int J Mol Sci 2022; 23:ijms23105658. [PMID: 35628473 PMCID: PMC9146104 DOI: 10.3390/ijms23105658] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 05/17/2022] [Accepted: 05/17/2022] [Indexed: 12/13/2022] Open
Abstract
Self-tolerance involves protection from self-reactive B and T cells via negative selection during differentiation, programmed cell death, and inhibition of regulatory T cells. The breakdown of immune tolerance triggers various autoimmune diseases, owing to a lack of distinction between self-antigens and non-self-antigens. Exosomes are non-particles that are approximately 50–130 nm in diameter. Extracellular vesicles can be used for in vivo cell-free transmission to enable intracellular delivery of proteins and nucleic acids, including microRNAs (miRNAs). miRNAs encapsulated in exosomes can regulate the molecular pathways involved in the immune response through post-transcriptional regulation. Herein, we sought to summarize and review the molecular mechanisms whereby exosomal miRNAs modulate the expression of genes involved in the immune response.
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Affiliation(s)
- Yasunari Matsuzaka
- Division of Molecular and Medical Genetics, Center for Gene and Cell Therapy, The Institute of Medical Science, University of Tokyo, Minato-ku 108-8639, Tokyo, Japan
- Correspondence: ; Tel.: +81-3-5449-5372
| | - Ryu Yashiro
- Administrative Section of Radiation Protection, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira 187-8551, Tokyo, Japan; or
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23
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Lai JJ, Chau ZL, Chen S, Hill JJ, Korpany KV, Liang N, Lin L, Lin Y, Liu JK, Liu Y, Lunde R, Shen W. Exosome Processing and Characterization Approaches for Research and Technology Development. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2022; 9:e2103222. [PMID: 35332686 PMCID: PMC9130923 DOI: 10.1002/advs.202103222] [Citation(s) in RCA: 234] [Impact Index Per Article: 78.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 01/28/2022] [Indexed: 05/05/2023]
Abstract
Exosomes are extracellular vesicles that share components of their parent cells and are attractive in biotechnology and biomedical research as potential disease biomarkers as well as therapeutic agents. Crucial to realizing this potential is the ability to manufacture high-quality exosomes; however, unlike biologics such as proteins, exosomes lack standardized Good Manufacturing Practices for their processing and characterization. Furthermore, there is a lack of well-characterized reference exosome materials to aid in selection of methods for exosome isolation, purification, and analysis. This review informs exosome research and technology development by comparing exosome processing and characterization methods and recommending exosome workflows. This review also provides a detailed introduction to exosomes, including their physical and chemical properties, roles in normal biological processes and in disease progression, and summarizes some of the on-going clinical trials.
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Affiliation(s)
- James J. Lai
- Department of BioengineeringUniversity of WashingtonSeattleWA98195USA
| | - Zoe L. Chau
- Department of BioengineeringUniversity of WashingtonSeattleWA98195USA
| | - Sheng‐You Chen
- Department of Mechanical EngineeringUniversity of WashingtonSeattleWA98195USA
| | - John J. Hill
- Department of BioengineeringUniversity of WashingtonSeattleWA98195USA
| | | | - Nai‐Wen Liang
- Department of Materials Science and EngineeringNational Tsing Hua UniversityHsinchu30013Taiwan
| | - Li‐Han Lin
- Department of Mechanical EngineeringNational Taiwan UniversityTaipei City10617Taiwan
| | - Yi‐Hsuan Lin
- Department of Engineering and System ScienceNational Tsing Hua UniversityHsinchu30013Taiwan
| | - Joanne K. Liu
- Department of BioengineeringUniversity of WashingtonSeattleWA98195USA
| | - Yu‐Chung Liu
- Department of Materials Science and EngineeringNational Tsing Hua UniversityHsinchu30013Taiwan
| | - Ruby Lunde
- Department of BioengineeringUniversity of WashingtonSeattleWA98195USA
| | - Wei‐Ting Shen
- Department of Biomedical Engineering and Environmental SciencesNational Tsing Hua UniversityHsinchu30013Taiwan
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24
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Petroušková P, Hudáková N, Maloveská M, Humeník F, Cizkova D. Non-Exosomal and Exosome-Derived miRNAs as Promising Biomarkers in Canine Mammary Cancer. Life (Basel) 2022; 12:life12040524. [PMID: 35455015 PMCID: PMC9032658 DOI: 10.3390/life12040524] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 03/29/2022] [Accepted: 03/30/2022] [Indexed: 02/06/2023] Open
Abstract
Canine mammary cancer (CMC), similar to human breast cancer (HBC) in many aspects, is the most common neoplasm associated with significant mortality in female dogs. Due to the limited therapy options, biomarkers are highly desirable for early clinical diagnosis or cancer progression monitoring. Since the discovery of microRNAs (miRNAs or miRs) as post-transcriptional gene regulators, they have become attractive biomarkers in oncological research. Except for intracellular miRNAs and cell-free miRNAs, exosome-derived miRNAs (exomiRs) have drawn much attention in recent years as biomarkers for cancer detection. Analysis of exosomes represents a non-invasive, pain-free, time- and money-saving alternative to conventional tissue biopsy. The purpose of this review is to provide a summary of miRNAs that come from non-exosomal sources (canine mammary tumor, mammary tumor cell lines or canine blood serum) and from exosomes as promising biomarkers of CMC based on the current literature. As is discussed, some of the miRNAs postulated as diagnostic or prognostic biomarkers in CMC were also altered in HBC (such as miR-21, miR-29b, miR-141, miR-429, miR-200c, miR-497, miR-210, miR-96, miR-18a, miR19b, miR-20b, miR-93, miR-101, miR-105a, miR-130a, miR-200c, miR-340, miR-486), which may be considered as potential disease-specific biomarkers in both CMC and HBC.
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Affiliation(s)
- Patrícia Petroušková
- Centre of Experimental and Clinical Regenerative Medicine, The University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, Slovakia; (P.P.); (N.H.); (M.M.); (F.H.)
| | - Nikola Hudáková
- Centre of Experimental and Clinical Regenerative Medicine, The University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, Slovakia; (P.P.); (N.H.); (M.M.); (F.H.)
| | - Marcela Maloveská
- Centre of Experimental and Clinical Regenerative Medicine, The University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, Slovakia; (P.P.); (N.H.); (M.M.); (F.H.)
| | - Filip Humeník
- Centre of Experimental and Clinical Regenerative Medicine, The University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, Slovakia; (P.P.); (N.H.); (M.M.); (F.H.)
| | - Dasa Cizkova
- Centre of Experimental and Clinical Regenerative Medicine, The University of Veterinary Medicine and Pharmacy, Komenského 73, 041 81 Košice, Slovakia; (P.P.); (N.H.); (M.M.); (F.H.)
- Institute of Neuroimmunology, Slovak Academy of Sciences, Dúbravská Cesta 9, 845 10 Bratislava, Slovakia
- Correspondence: ; Tel.: +421-918-752-157
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25
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Alghamdi M, Alamry SA, Bahlas SM, Uversky VN, Redwan EM. Circulating extracellular vesicles and rheumatoid arthritis: a proteomic analysis. Cell Mol Life Sci 2021; 79:25. [PMID: 34971426 PMCID: PMC11072894 DOI: 10.1007/s00018-021-04020-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 10/28/2021] [Accepted: 10/29/2021] [Indexed: 12/14/2022]
Abstract
Circulating extracellular vesicles (EVs) are membrane-bound nanoparticles secreted by most cells for intracellular communication and transportation of biomolecules. EVs carry proteins, lipids, nucleic acids, and receptors that are involved in human physiology and pathology. EV cargo is variable and highly related to the type and state of the cellular origin. Three subtypes of EVs have been identified: exosomes, microvesicles, and apoptotic bodies. Exosomes are the smallest and the most well-studied class of EVs that regulate different biological processes and participate in several diseases, such as cancers and autoimmune diseases. Proteomic analysis of exosomes succeeded in profiling numerous types of proteins involved in disease development and prognosis. In rheumatoid arthritis (RA), exosomes revealed a potential function in joint inflammation. These EVs possess a unique function, as they can transfer specific autoantigens and mediators between distant cells. Current proteomic data demonstrated that exosomes could provide beneficial effects against autoimmunity and exert an immunosuppressive action, particularly in RA. Based on these observations, effective therapeutic strategies have been developed for arthritis and other inflammatory disorders.
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Affiliation(s)
- Mohammed Alghamdi
- Biological Sciences Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah, 21589, Saudi Arabia
- Laboratory Department, University Medical Services Center, King Abdulaziz University, P.O. Box 80200, Jeddah, 21589, Saudi Arabia
| | - Sultan Abdulmughni Alamry
- Immunology Diagnostic Laboratory Department, King Abdulaziz University Hospital, P.O Box 80215, Jeddah, 21589, Saudi Arabia
| | - Sami M Bahlas
- Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, P.O. Box 80215, Jeddah, 21589, Saudi Arabia
| | - Vladimir N Uversky
- Biological Sciences Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah, 21589, Saudi Arabia
- Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
| | - Elrashdy M Redwan
- Biological Sciences Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah, 21589, Saudi Arabia.
- Therapeutic and Protective Proteins Laboratory, Protein Research Department, Genetic Engineering and Biotechnology Research Institute, City for Scientific Research and Technology Applications, New Borg EL-Arab, 21934, Alexandria, Egypt.
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26
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Zou J, Peng H, Liu Y. The Roles of Exosomes in Immunoregulation and Autoimmune Thyroid Diseases. Front Immunol 2021; 12:757674. [PMID: 34867996 PMCID: PMC8634671 DOI: 10.3389/fimmu.2021.757674] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 10/29/2021] [Indexed: 12/21/2022] Open
Abstract
Exosomes are extracellular microvesicles (30-150 nm) released from cells that contain proteins, lipids, RNA and DNA. They can deliver bioactive molecules and serve as carriers facilitating cell-cell communication, such as antigen presentation, inflammatory activation, autoimmune diseases (AIDs) and tumor metastasis. Recently, much attention has been attracted to the biology and functions of exosomes in immune regulation and AIDs, including autoimmune thyroid diseases (AITDs). Some studies have shown that exosomes are involved in the occurrence and development of AITDs, but they are still in the preliminary stage of exploration. This review mainly introduces the association of exosomes with immune regulation and emphasizes the potential role of exosomes in AITDs, aiming to provide new research strategies and directions for the pathogenesis and early diagnosis of AITDs.
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Affiliation(s)
- Junli Zou
- Department of Endocrinology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang Medical School of Nanjing Medical University, Zhenjiang, China
| | - Huiyong Peng
- Department of Laboratory Medicine, The Affiliated People's Hospital of Jiangsu University, Zhenjiang Medical School of Nanjing Medical University, Zhenjiang, China.,Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Yingzhao Liu
- Department of Endocrinology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang Medical School of Nanjing Medical University, Zhenjiang, China
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Foo JB, Looi QH, How CW, Lee SH, Al-Masawa ME, Chong PP, Law JX. Mesenchymal Stem Cell-Derived Exosomes and MicroRNAs in Cartilage Regeneration: Biogenesis, Efficacy, miRNA Enrichment and Delivery. Pharmaceuticals (Basel) 2021; 14:1093. [PMID: 34832875 PMCID: PMC8618513 DOI: 10.3390/ph14111093] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 10/25/2021] [Accepted: 10/26/2021] [Indexed: 02/07/2023] Open
Abstract
Exosomes are the small extracellular vesicles secreted by cells for intercellular communication. Exosomes are rich in therapeutic cargos such as microRNA (miRNA), long non-coding RNA (lncRNA), small interfering RNA (siRNA), DNA, protein, and lipids. Recently, many studies have focused on miRNAs as a promising therapeutic factor to support cartilage regeneration. Exosomes are known to contain a substantial amount of a variety of miRNAs. miRNAs regulate the post-transcriptional gene expression by base-pairing with the target messenger RNA (mRNA), leading to gene silencing. Several exosomal miRNAs have been found to play a role in cartilage regeneration by promoting chondrocyte proliferation and matrix secretion, reducing scar tissue formation, and subsiding inflammation. The exosomal miRNA cargo can be modulated using techniques such as cell transfection and priming as well as post-secretion modifications to upregulate specific miRNAs to enhance the therapeutic effect. Exosomes are delivered to the joints through direct injection or via encapsulation within a scaffold for sustained release. To date, exosome therapy for cartilage injuries has yet to be optimized as the ideal cell source for exosomes, and the dose and method of delivery have yet to be identified. More importantly, a deeper understanding of the role of exosomal miRNAs in cartilage repair is paramount for the development of more effective exosome therapy.
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Affiliation(s)
- Jhi Biau Foo
- School of Pharmacy, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya 47500, Malaysia;
- Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya 47500, Malaysia;
| | - Qi Hao Looi
- My Cytohealth Sdn. Bhd., D353a, Menara Suezcap 1, KL Gateway, no. 2, Jalan Kerinchi, Gerbang Kerinchi Lestari, Kuala Lumpur 59200, Malaysia;
- National Orthopaedic Centre of Excellence in Research and Learning (NOCERAL), Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia
| | - Chee Wun How
- School of Pharmacy, Monash University Malaysia, Bandar Sunway 47500, Malaysia;
| | - Sau Har Lee
- Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya 47500, Malaysia;
- Faculty of Health and Medical Sciences, School of Biosciences, Taylor’s University, Subang Jaya 47500, Malaysia;
| | - Maimonah Eissa Al-Masawa
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Kuala Lumpur 56000, Malaysia;
| | - Pei Pei Chong
- Faculty of Health and Medical Sciences, School of Biosciences, Taylor’s University, Subang Jaya 47500, Malaysia;
| | - Jia Xian Law
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Kuala Lumpur 56000, Malaysia;
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28
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Jiang C, Zhang N, Hu X, Wang H. Tumor-associated exosomes promote lung cancer metastasis through multiple mechanisms. Mol Cancer 2021; 20:117. [PMID: 34511114 PMCID: PMC8436438 DOI: 10.1186/s12943-021-01411-w] [Citation(s) in RCA: 114] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 08/19/2021] [Indexed: 02/06/2023] Open
Abstract
As an important medium of intercellular communication, exosomes play an important role in information transmission between tumor cells and their microenvironment. Tumor metastasis is a serious influencing factor for poor treatment effect and shortened survival. Lung cancer is a major malignant tumor that seriously threatens human health. The study of the underlying mechanisms of exosomes in tumor genesis and development may provide new ideas for early and effective diagnosis and treatment of lung cancer metastasis. Many studies have shown that tumor-derived exosomes promote lung cancer development through a number of processes. By promoting epithelial-mesenchymal transition of tumor cells, they induce angiogenesis, establishment of the pretransfer microenvironment, and immune escape. This understanding enables researchers to better understand the mechanism of lung cancer metastasis and explore new treatments for clinical application. In this article, we systematically review current research progress of tumor-derived exosomes in metastasis of lung cancer. Although positive progress has been made toward understanding the mechanism of exosomes in lung cancer metastasis, systematic basic research and clinical translational research remains lacking and are needed to translate our scientific understanding toward applications in the clinical diagnosis and treatment of lung cancer metastasis in the near future.
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Affiliation(s)
- Chunyang Jiang
- Department of Thoracic Surgery, Tianjin Union Medical Center, Nankai University, 190 Jieyuan Road, Hongqiao District, Tianjin, 300121, China.
| | - Na Zhang
- Department of Respiratory Medicine, Tianjin Union Medical Center, Nankai University, 190 Jieyuan Road, Hongqiao District, Tianjin, 300121, China
| | - Xiaoli Hu
- Department of Respiratory Medicine, The Second People's Hospital of Linhai City, 198 Dubei Road, Linhai, 317016, Zhejiang Province, China
| | - Hongyan Wang
- Department of Thoracic Surgery, The 4th Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, Hebei Province, China.
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Zhang LY, Yang X, Wang SB, Chen H, Pan HY, Hu ZM. Membrane Derived Vesicles as Biomimetic Carriers for Targeted Drug Delivery System. Curr Top Med Chem 2021; 20:2472-2492. [PMID: 32962615 DOI: 10.2174/1568026620666200922113054] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 03/25/2020] [Accepted: 04/25/2020] [Indexed: 02/06/2023]
Abstract
Extracellular vesicles (EVs) are membrane vesicles (MVs) playing important roles in various cellular and molecular functions in cell-to-cell signaling and transmitting molecular signals to adjacent as well as distant cells. The preserved cell membrane characteristics in MVs derived from live cells, give them great potential in biological applications. EVs are nanoscale particulates secreted from living cells and play crucial roles in several important cellular functions both in physiological and pathological states. EVs are the main elements in intercellular communication in which they serve as carriers for various endogenous cargo molecules, such as RNAs, proteins, carbohydrates, and lipids. High tissue tropism capacity that can be conveniently mediated by surface molecules, such as integrins and glycans, is a unique feature of EVs that makes them interesting candidates for targeted drug delivery systems. The cell-derived giant MVs have been exploited as vehicles for delivery of various anticancer agents and imaging probes and for implementing combinational phototherapy for targeted cancer treatment. Giant MVs can efficiently encapsulate therapeutic drugs and deliver them to target cells through the membrane fusion process to synergize photodynamic/photothermal treatment under light exposure. EVs can load diagnostic or therapeutic agents using different encapsulation or conjugation methods. Moreover, to prolong the blood circulation and enhance the targeting of the loaded agents, a variety of modification strategies can be exploited. This paper reviews the EVs-based drug delivery strategies in cancer therapy. Biological, pharmacokinetics and physicochemical characteristics, isolation techniques, engineering, and drug loading strategies of EVs are discussed. The recent preclinical and clinical progresses in applications of EVs and oncolytic virus therapy based on EVs, the clinical challenges and perspectives are discussed.
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Affiliation(s)
- Le-Yi Zhang
- Department of General Surgery, Chun’an First People’s Hospital (Zhejiang Provincial People's Hospital Chun’an
Branch), Hangzhou 311700, China
| | - Xue Yang
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
| | - Shi-Bing Wang
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
| | - Hong Chen
- Department of Stomatology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou
Medical College, Hangzhou 310014, China
| | - Hong-Ying Pan
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China,Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
| | - Zhi-Ming Hu
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China,Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
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30
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Zhong Y, Li X, Wang F, Wang S, Wang X, Tian X, Bai S, Miao D, Fan J. Emerging Potential of Exosomes on Adipogenic Differentiation of Mesenchymal Stem Cells. Front Cell Dev Biol 2021; 9:649552. [PMID: 34239869 PMCID: PMC8258133 DOI: 10.3389/fcell.2021.649552] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 05/28/2021] [Indexed: 12/20/2022] Open
Abstract
The mesenchymal stem cells have multidirectional differentiation potential and can differentiate into adipocytes, osteoblasts, cartilage tissue, muscle cells and so on. The adipogenic differentiation of mesenchymal stem cells is of great significance for the construction of tissue-engineered fat and the treatment of soft tissue defects. Exosomes are nanoscale vesicles secreted by cells and widely exist in body fluids. They are mainly involved in cell communication processes and transferring cargo contents to recipient cells. In addition, exosomes can also promote tissue and organ regeneration. Recent studies have shown that various exosomes can influence the adipogenic differentiation of stem cells. In this review, the effects of exosomes on stem cell differentiation, especially on adipogenic differentiation, will be discussed, and the mechanisms and conclusions will be drawn. The main purpose of studying the role of these exosomes is to understand more comprehensively the influencing factors existing in the process of stem cell differentiation into adipocytes and provide a new idea in adipose tissue engineering research.
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Affiliation(s)
- Yuxuan Zhong
- Department of Tissue Engineering, School of Fundamental Science, China Medical University, Shenyang, China
| | - Xiang Li
- Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China
| | - Fanglin Wang
- Department of Tissue Engineering, School of Fundamental Science, China Medical University, Shenyang, China
| | - Shoushuai Wang
- Department of Tissue Engineering, School of Fundamental Science, China Medical University, Shenyang, China
| | - Xiaohong Wang
- Department of Tissue Engineering, School of Fundamental Science, China Medical University, Shenyang, China
| | - Xiaohong Tian
- Department of Tissue Engineering, School of Fundamental Science, China Medical University, Shenyang, China
| | - Shuling Bai
- Department of Tissue Engineering, School of Fundamental Science, China Medical University, Shenyang, China
| | - Di Miao
- China Medical University-The Queen's University of Belfast Joint College-Combination, Shenyang, China
| | - Jun Fan
- Department of Tissue Engineering, School of Fundamental Science, China Medical University, Shenyang, China
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31
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Ding X, Jing N, Shen A, Guo F, Song Y, Pan M, Ma X, Zhao L, Zhang H, Wu L, Qin G, Zhao Y. MiR-21-5p in macrophage-derived extracellular vesicles affects podocyte pyroptosis in diabetic nephropathy by regulating A20. J Endocrinol Invest 2021; 44:1175-1184. [PMID: 32930981 DOI: 10.1007/s40618-020-01401-7] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 08/19/2020] [Indexed: 01/01/2023]
Abstract
OBJECTIVES Podocyte pyroptosis, characterized by inflammasome activation, plays an important role in inflammation-mediated diabetic nephropathy (DN). Our study aimed to investigate whether miR-21-5p in macrophage-derived extracellular vesicles (EVs) could affect podocyte injury in DN. METHODS EVs were extracted after the treatment of RAW 264.7 (mouse macrophage line) with high glucose (HG). The podocyte pyroptosis was determined using the flow cytometry and the western blot. After the knockdown of miR-21-5p in HG-induced RAW264.7 cells, we injected the extracted EVs into DN model mice. RESULTS The level of miR-21-5p was higher in HG-stimulated macrophage-derived EVs than in normal glucose-cultured macrophage-derived EVs. The co-culture of EVs and podocytes promoted reactive oxygen species (ROS) production and activation of inflammatory in MPC5 cells (mouse podocyte line). However, restraint of miR-21-5p in EVs reduced ROS production and inhibit inflammasome activation in MPC5 cells, thereby reducing podocytes injury. Meanwhile, we found that miR-21-5p inhibited the A20 expression through binding with its 3'-untranslated regions in MPC5 cells. Further studies showed that A20 was also involved in the regulation of miR-21-5p of RAW 264.7-derived EVs on MPC5 injury. At the same time, it was also proved in the DN model mice that miR-21-5p in macrophage-derived EVs could regulate podocyte injury. CONCLUSION MiR-21-5p in macrophage-derived EVs can regulate pyroptosis-mediated podocyte injury by A20 in DN.
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Affiliation(s)
- X Ding
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan, People's Republic of China
| | - N Jing
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan, People's Republic of China
| | - A Shen
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan, People's Republic of China
| | - F Guo
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan, People's Republic of China
| | - Y Song
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan, People's Republic of China
| | - M Pan
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan, People's Republic of China
| | - X Ma
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan, People's Republic of China
| | - L Zhao
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan, People's Republic of China
| | - H Zhang
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan, People's Republic of China
| | - L Wu
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan, People's Republic of China
| | - G Qin
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan, People's Republic of China
| | - Y Zhao
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan, People's Republic of China.
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Giacobino C, Canta M, Fornaguera C, Borrós S, Cauda V. Extracellular Vesicles and Their Current Role in Cancer Immunotherapy. Cancers (Basel) 2021; 13:cancers13092280. [PMID: 34068657 PMCID: PMC8126043 DOI: 10.3390/cancers13092280] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 05/03/2021] [Accepted: 05/07/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary In recent years, immunotherapy has shown great advancement, becoming a powerful tool to combat cancer. In this context, the use of biologically derived vesicles has also acquired importance for cancer immunotherapy. Extracellular vesicles are thus proposed to transport molecules able to trigger an immune response and thus fight cancer cells. As a particular immunotherapeutic approach, a new technique also consists in the exploitation of extracellular vesicles as new cancer vaccines. The present review provides basic notions on cancer immunotherapy and describes several clinical trials in which therapeutic anticancer vaccines are tested. In particular, the potential of extracellular vesicles-based therapeutic vaccines in the treatment of cancer patients is highlighted, even with advanced stage-cancer. A focus on the clinical studies, already completed or still in progress, is offered and a systematic collection and reorganization of the present literature on this topic is proposed to the reader. Abstract Extracellular vesicles (EVs) are natural particles formed by the lipid bilayer and released from almost all cell types to the extracellular environment both under physiological conditions and in presence of a disease. EVs are involved in many biological processes including intercellular communication, acting as natural carriers in the transfer of various biomolecules such as DNA, various RNA types, proteins and different phospholipids. Thanks to their transfer and targeting abilities, they can be employed in drug and gene delivery and have been proposed for the treatment of different diseases, including cancer. Recently, the use of EVs as biological carriers has also been extended to cancer immunotherapy. This new technique of cancer treatment involves the use of EVs to transport molecules capable of triggering an immune response to damage cancer cells. Several studies have analyzed the possibility of using EVs in new cancer vaccines, which represent a particular form of immunotherapy. In the literature there are only few publications that systematically group and collectively discuss these studies. Therefore, the purpose of this review is to illustrate and give a partial reorganization to what has been produced in the literature so far. We provide basic notions on cancer immunotherapy and describe some clinical trials in which therapeutic cancer vaccines are tested. We thus focus attention on the potential of EV-based therapeutic vaccines in the treatment of cancer patients, overviewing the clinically relevant trials, completed or still in progress, which open up new perspectives in the fight against cancer.
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Affiliation(s)
- Carla Giacobino
- Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin, Italy; (C.G.); (M.C.)
| | - Marta Canta
- Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin, Italy; (C.G.); (M.C.)
| | - Cristina Fornaguera
- Grup d’Enginyeria de Materials (Gemat), Institut Químic de Sarrià (IQS), Universitat Ramon Llull (URL), Via Augusta 390, 08017 Barcelona, Spain; (C.F.); (S.B.)
| | - Salvador Borrós
- Grup d’Enginyeria de Materials (Gemat), Institut Químic de Sarrià (IQS), Universitat Ramon Llull (URL), Via Augusta 390, 08017 Barcelona, Spain; (C.F.); (S.B.)
| | - Valentina Cauda
- Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin, Italy; (C.G.); (M.C.)
- Correspondence:
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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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The Mystery of Red Blood Cells Extracellular Vesicles in Sleep Apnea with Metabolic Dysfunction. Int J Mol Sci 2021; 22:ijms22094301. [PMID: 33919065 PMCID: PMC8122484 DOI: 10.3390/ijms22094301] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 04/15/2021] [Accepted: 04/16/2021] [Indexed: 12/12/2022] Open
Abstract
Sleep is very important for overall health and quality of life, while sleep disorder has been associated with several human diseases, namely cardiovascular, metabolic, cognitive, and cancer-related alterations. Obstructive sleep apnea (OSA) is the most common respiratory sleep-disordered breathing, which is caused by the recurrent collapse of the upper airway during sleep. OSA has emerged as a major public health problem and increasing evidence suggests that untreated OSA can lead to the development of various diseases including neurodegenerative diseases. In addition, OSA may lead to decreased blood oxygenation and fragmentation of the sleep cycle. The formation of free radicals or reactive oxygen species (ROS) can emerge and react with nitric oxide (NO) to produce peroxynitrite, thereby diminishing the bioavailability of NO. Hypoxia, the hallmark of OSA, refers to a decline of tissue oxygen saturation and affects several types of cells, playing cell-to-cell communication a vital role in the outcome of this interplay. Red blood cells (RBCs) are considered transporters of oxygen and nutrients to the tissues, and these RBCs are important interorgan communication systems with additional functions, including participation in the control of systemic NO metabolism, redox regulation, blood rheology, and viscosity. RBCs have been shown to induce endothelial dysfunction and increase cardiac injury. The mechanistic links between changes of RBC functional properties and cardiovascular are largely unknown. Extracellular vesicles (EVs) are secreted by most cell types and released in biological fluids both under physiological and pathological conditions. EVs are involved in intercellular communication by transferring complex cargoes including proteins, lipids, and nucleic acids from donor cells to recipient cells. Advancing our knowledge about mechanisms of RBC-EVs formation and their pathophysiological relevance may help to shed light on circulating EVs and to translate their application to clinical practice. We will focus on the potential use of RBC-EVs as valuable diagnostic and prognostic biomarkers and state-specific cargoes, and possibilities as therapeutic vehicles for drug and gene delivery. The use of RBC-EVs as a precision medicine for the diagnosis and treatment of the patient with sleep disorder will improve the prognosis and the quality of life in patients with cardiovascular disease (CVD).
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Jahromi LP, Shahbazi M, Maleki A, Azadi A, Santos HA. Chemically Engineered Immune Cell-Derived Microrobots and Biomimetic Nanoparticles: Emerging Biodiagnostic and Therapeutic Tools. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2021; 8:2002499. [PMID: 33898169 PMCID: PMC8061401 DOI: 10.1002/advs.202002499] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 11/26/2020] [Indexed: 05/16/2023]
Abstract
Over the past decades, considerable attention has been dedicated to the exploitation of diverse immune cells as therapeutic and/or diagnostic cell-based microrobots for hard-to-treat disorders. To date, a plethora of therapeutics based on alive immune cells, surface-engineered immune cells, immunocytes' cell membranes, leukocyte-derived extracellular vesicles or exosomes, and artificial immune cells have been investigated and a few have been introduced into the market. These systems take advantage of the unique characteristics and functions of immune cells, including their presence in circulating blood and various tissues, complex crosstalk properties, high affinity to different self and foreign markers, unique potential of their on-demand navigation and activity, production of a variety of chemokines/cytokines, as well as being cytotoxic in particular conditions. Here, the latest progress in the development of engineered therapeutics and diagnostics inspired by immune cells to ameliorate cancer, inflammatory conditions, autoimmune diseases, neurodegenerative disorders, cardiovascular complications, and infectious diseases is reviewed, and finally, the perspective for their clinical application is delineated.
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Affiliation(s)
- Leila Pourtalebi Jahromi
- Drug Research ProgramDivision of Pharmaceutical Chemistry and TechnologyFaculty of PharmacyUniversity of HelsinkiHelsinkiFI‐00014Finland
- Pharmaceutical Sciences Research CenterShiraz University of Medical SciencesShiraz71468‐64685Iran
- Present address:
Helmholtz Institute for Pharmaceutical Research SaarlandHelmholtz Centre for Infection ResearchBiogenic Nanotherapeutics GroupCampus E8.1Saarbrücken66123Germany
| | - Mohammad‐Ali Shahbazi
- Drug Research ProgramDivision of Pharmaceutical Chemistry and TechnologyFaculty of PharmacyUniversity of HelsinkiHelsinkiFI‐00014Finland
- Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC)Zanjan University of Medical SciencesZanjan45139‐56184Iran
| | - Aziz Maleki
- Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC)Zanjan University of Medical SciencesZanjan45139‐56184Iran
| | - Amir Azadi
- Pharmaceutical Sciences Research CenterShiraz University of Medical SciencesShiraz71468‐64685Iran
- Department of PharmaceuticsSchool of PharmacyShiraz University of Medical SciencesShiraz71468‐64685Iran
| | - Hélder A. Santos
- Drug Research ProgramDivision of Pharmaceutical Chemistry and TechnologyFaculty of PharmacyUniversity of HelsinkiHelsinkiFI‐00014Finland
- Helsinki Institute of Life Science (HiLIFE)University of HelsinkiHelsinkiFI‐00014Finland
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Gaurav I, Thakur A, Iyaswamy A, Wang X, Chen X, Yang Z. Factors Affecting Extracellular Vesicles Based Drug Delivery Systems. Molecules 2021; 26:molecules26061544. [PMID: 33799765 PMCID: PMC7999478 DOI: 10.3390/molecules26061544] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/18/2021] [Accepted: 02/19/2021] [Indexed: 02/07/2023] Open
Abstract
Extracellular vesicles (EVs) play major roles in intracellular communication and participate in several biological functions in both normal and pathological conditions. Surface modification of EVs via various ligands, such as proteins, peptides, or aptamers, offers great potential as a means to achieve targeted delivery of therapeutic cargo, i.e., in drug delivery systems (DDS). This review summarizes recent studies pertaining to the development of EV-based DDS and its advantages compared to conventional nano drug delivery systems (NDDS). First, we compare liposomes and exosomes in terms of their distinct benefits in DDS. Second, we analyze what to consider for achieving better isolation, yield, and characterization of EVs for DDS. Third, we summarize different methods for the modification of surface of EVs, followed by discussion about different origins of EVs and their role in developing DDS. Next, several major methods for encapsulating therapeutic cargos in EVs have been summarized. Finally, we discuss key challenges and pose important open questions which warrant further investigation to develop more effective EV-based DDS.
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Affiliation(s)
- Isha Gaurav
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China; (I.G.); (A.I.); (X.W.); (X.C.)
| | - Abhimanyu Thakur
- Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation-CAS Limited, Hong Kong, China;
| | - Ashok Iyaswamy
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China; (I.G.); (A.I.); (X.W.); (X.C.)
- Mr. & Mrs. Ko Chi-Ming Centre for Parkinson’s Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
| | - Xuehan Wang
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China; (I.G.); (A.I.); (X.W.); (X.C.)
| | - Xiaoyu Chen
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China; (I.G.); (A.I.); (X.W.); (X.C.)
| | - Zhijun Yang
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China; (I.G.); (A.I.); (X.W.); (X.C.)
- Changshu Research Institute, Hong Kong Baptist University, Changshu Economic and Technological Development (CETD) Zone, Changshu 215500, Jiangsu Province, China
- Correspondence: ; Tel.: +852-3411-2961
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Gebeyehu A, Kommineni N, Bagde A, Meckes DG, Sachdeva MS. Role of Exosomes for Delivery of Chemotherapeutic Drugs. Crit Rev Ther Drug Carrier Syst 2021; 38:53-97. [PMID: 34375513 PMCID: PMC8691065 DOI: 10.1615/critrevtherdrugcarriersyst.2021036301] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Exosomes are endogenous extracellular vesicles (30-100 nm) composed with membrane lipid bilayer which carry vesicular proteins, enzymes, mRNA, miRNA and nucleic acids. They act as messengers for intra- and inter-cellular communication. In addition to their physiological roles, exosomes have the potential to encapsulate and deliver small chemotherapeutic drugs and biological molecules such as proteins and nucleic acid-based drugs to the recipient tissue or organs. Due to their biological properties, exosomes have better organotropism, homing capacity, cellular uptake and cargo release ability than other synthetic nano-drug carriers such as liposomes, micelles and nanogels. The secretion of tumor-derived exosomes is increased in the hypoxic and acidic tumor microenvironment, which can be used as a target for nontoxic and nonimmunogenic drug delivery vehicles for various cancers. Moreover, exosomes have the potential to carry both hydrophilic and hydrophobic chemotherapeutic drugs, bypass RES effect and bypass BBB. Exosomes can be isolated from other types of EVs and cell debris based on their size, density and specific surface proteins through ultracentrifugation, density gradient separation, precipitation, immunoaffinity interaction and gel filtration. Drugs can be loaded into exosomes at the biogenesis stage or with the isolated exosomes by incubation, electroporation, extrusion or sonication methods. Finally, exosomal cargo vehicles can be characterized by ultrastructural microscopic analysis. In this review we intend to summarize the inception, structure and function of the exosomes, role of exosomes in immunological regulation and cancer, methods of isolation and characterization of exosomes and products under clinical trials. This review will provide an inclusive insight of exosomes in drug delivery.
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Affiliation(s)
- Aragaw Gebeyehu
- College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA
| | - Nagavendra Kommineni
- College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA
| | - Arvind Bagde
- College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA
| | - David G. Meckes
- Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306, USA
| | - Mandip Singh Sachdeva
- College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA
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Gong P, Wang Y, Zhang P, Yang Z, Deng W, Sun Z, Yang M, Li X, Ma G, Deng G, Dong S, Cai L, Jiang W. Immunocyte Membrane-Coated Nanoparticles for Cancer Immunotherapy. Cancers (Basel) 2020; 13:E77. [PMID: 33396603 PMCID: PMC7794746 DOI: 10.3390/cancers13010077] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 12/15/2020] [Accepted: 12/17/2020] [Indexed: 12/16/2022] Open
Abstract
Despite the advances in surface bioconjugation of synthetic nanoparticles for targeted drug delivery, simple biological functionalization is still insufficient to replicate complex intercellular interactions naturally. Therefore, these foreign nanoparticles are inevitably exposed to the immune system, which results in phagocytosis by the reticuloendothelial system and thus, loss of their biological significance. Immunocyte membranes play a key role in intercellular interactions, and can protect foreign nanomaterials as a natural barrier. Therefore, biomimetic nanotechnology based on cell membranes has developed rapidly in recent years. This paper summarizes the development of immunocyte membrane-coated nanoparticles in the immunotherapy of tumors. We will introduce several immunocyte membrane-coated nanocarriers and review the challenges to their large-scale preparation and application.
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Affiliation(s)
- Ping Gong
- Guangdong Key Laboratory of Nanomedicine, Shenzhen Engineering Laboratory of Nanomedicine and Nanoformulations, CAS-HK Joint Lab for Biomaterials, CAS Key Laboratory of Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; (P.Z.); (Z.S.); (G.M.); (G.D.); (L.C.)
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, 2280 Inwood Road, Dallas, TX 75235, USA; (Y.W.); (Z.Y.); (W.D.); (M.Y.); (X.L.); (S.D.)
| | - Yifan Wang
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, 2280 Inwood Road, Dallas, TX 75235, USA; (Y.W.); (Z.Y.); (W.D.); (M.Y.); (X.L.); (S.D.)
| | - Pengfei Zhang
- Guangdong Key Laboratory of Nanomedicine, Shenzhen Engineering Laboratory of Nanomedicine and Nanoformulations, CAS-HK Joint Lab for Biomaterials, CAS Key Laboratory of Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; (P.Z.); (Z.S.); (G.M.); (G.D.); (L.C.)
| | - Zhaogang Yang
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, 2280 Inwood Road, Dallas, TX 75235, USA; (Y.W.); (Z.Y.); (W.D.); (M.Y.); (X.L.); (S.D.)
| | - Weiye Deng
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, 2280 Inwood Road, Dallas, TX 75235, USA; (Y.W.); (Z.Y.); (W.D.); (M.Y.); (X.L.); (S.D.)
| | - Zhihong Sun
- Guangdong Key Laboratory of Nanomedicine, Shenzhen Engineering Laboratory of Nanomedicine and Nanoformulations, CAS-HK Joint Lab for Biomaterials, CAS Key Laboratory of Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; (P.Z.); (Z.S.); (G.M.); (G.D.); (L.C.)
- Yantai Yuhuangding Hospital, Yantai 264000, China
| | - Mingming Yang
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, 2280 Inwood Road, Dallas, TX 75235, USA; (Y.W.); (Z.Y.); (W.D.); (M.Y.); (X.L.); (S.D.)
| | - Xuefeng Li
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, 2280 Inwood Road, Dallas, TX 75235, USA; (Y.W.); (Z.Y.); (W.D.); (M.Y.); (X.L.); (S.D.)
| | - Gongcheng Ma
- Guangdong Key Laboratory of Nanomedicine, Shenzhen Engineering Laboratory of Nanomedicine and Nanoformulations, CAS-HK Joint Lab for Biomaterials, CAS Key Laboratory of Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; (P.Z.); (Z.S.); (G.M.); (G.D.); (L.C.)
| | - Guanjun Deng
- Guangdong Key Laboratory of Nanomedicine, Shenzhen Engineering Laboratory of Nanomedicine and Nanoformulations, CAS-HK Joint Lab for Biomaterials, CAS Key Laboratory of Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; (P.Z.); (Z.S.); (G.M.); (G.D.); (L.C.)
| | - Shiyan Dong
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, 2280 Inwood Road, Dallas, TX 75235, USA; (Y.W.); (Z.Y.); (W.D.); (M.Y.); (X.L.); (S.D.)
| | - Lintao Cai
- Guangdong Key Laboratory of Nanomedicine, Shenzhen Engineering Laboratory of Nanomedicine and Nanoformulations, CAS-HK Joint Lab for Biomaterials, CAS Key Laboratory of Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; (P.Z.); (Z.S.); (G.M.); (G.D.); (L.C.)
| | - Wen Jiang
- Department of Radiation Oncology, University of Texas Southwestern Medical Center, 2280 Inwood Road, Dallas, TX 75235, USA; (Y.W.); (Z.Y.); (W.D.); (M.Y.); (X.L.); (S.D.)
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Keup C, Kimmig R, Kasimir-Bauer S. Liquid Biopsies to Evaluate Immunogenicity of Gynecological/Breast Tumors: On the Way to Blood-Based Biomarkers for Immunotherapies. Breast Care (Basel) 2020; 15:470-480. [PMID: 33223990 PMCID: PMC7650128 DOI: 10.1159/000510509] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Accepted: 07/28/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Despite the assumption of breast cancer (BC) as a cold, non-immunogenic tumor, immune checkpoint inhibitor (ICI) therapy is favorable for a subgroup of patients. Immunohistochemical assessment of the programmed cell death ligand 1 (PD-L1) is the only approved companion diagnostic for anti-PD-L1 therapy in metastatic triple-negative BC; however, challenges regarding the standardization of PD-L1 scoring in tumor tissue still remain. Consequently, to select patients most likely to respond to ICI, blood-based biomarkers are urgently needed. SUMMARY AND KEY MESSAGES Liquid biopsy, comprising circulating immune cells, circulating tumor cells and extracellular vesicles, as well as their surface proteins, is of high potential, and these analytes were already shown to be molecular correlates or regulators of the evasion from antitumoral immune reaction. Liquid biopsy, also enabling the evaluation of tumor mutational burden (TMB), microsatellite instability, and the T-cell receptor repertoire, allows serial sampling for monitoring purposes and reflects intra-tumoral heterogeneity which qualifies as marker for immunogenicity. Only a very few studies have already elucidated the potential of these analytes as biomarkers under ICI therapy. Nonetheless, the topic is of growing interest and has high relevance for the future. However, for clinical implementation, these multifarious analytes first need to pass robust standardization and validation procedures.
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Affiliation(s)
| | | | - Sabine Kasimir-Bauer
- Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany
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40
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Nelson BC, Maragh S, Ghiran IC, Jones JC, DeRose PC, Elsheikh E, Vreeland WN, Wang L. Measurement and standardization challenges for extracellular vesicle therapeutic delivery vectors. Nanomedicine (Lond) 2020; 15:2149-2170. [PMID: 32885720 PMCID: PMC7546159 DOI: 10.2217/nnm-2020-0206] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 07/10/2020] [Indexed: 12/21/2022] Open
Abstract
Extracellular vesicles (EVs), such as exosomes and microvesicles, are nonreplicating lipid bilayer particles shed by most cell types which have the potential to revolutionize the development and efficient delivery of clinical therapeutics. This article provides an introduction to the landscape of EV-based vectors under development for the delivery of protein- and nucleic acid-based therapeutics. We highlight some of the most pressing measurement and standardization challenges that limit the translation of EVs to the clinic. Current challenges limiting development of EVs for drug delivery are the lack of: standardized cell-based platforms for the production of EV-based therapeutics; EV reference materials that allow researchers/manufacturers to validate EV measurements and standardized measurement systems for determining the molecular composition of EVs.
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Affiliation(s)
- Bryant C Nelson
- National Institute of Standards & Technology, Material Measurement Laboratory, Gaithersburg, MD 20899, USA
| | - Samantha Maragh
- National Institute of Standards & Technology, Material Measurement Laboratory, Gaithersburg, MD 20899, USA
| | - Ionita C Ghiran
- Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
| | - Jennifer C Jones
- National Institutes of Health, National Cancer Institute, Bethesda, MD 20892, USA
| | - Paul C DeRose
- National Institute of Standards & Technology, Material Measurement Laboratory, Gaithersburg, MD 20899, USA
| | - Elzafir Elsheikh
- National Institute of Standards & Technology, Material Measurement Laboratory, Gaithersburg, MD 20899, USA
| | - Wyatt N Vreeland
- National Institute of Standards & Technology, Material Measurement Laboratory, Gaithersburg, MD 20899, USA
| | - Lili Wang
- National Institute of Standards & Technology, Material Measurement Laboratory, Gaithersburg, MD 20899, USA
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Huang Y, Li R, Ye S, Lin S, Yin G, Xie Q. Recent Advances in the Use of Exosomes in Sjögren's Syndrome. Front Immunol 2020; 11:1509. [PMID: 32903777 PMCID: PMC7438915 DOI: 10.3389/fimmu.2020.01509] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 06/09/2020] [Indexed: 02/05/2023] Open
Abstract
Sjögren's syndrome (SS) is a chronic autoimmune disorder of the exocrine glands mediated by lymphocytic infiltrates damaging the body tissues and affecting the life quality of patients. Although traditional methods of diagnosis and treatment for SS are effective, in the time of personalized medicine, new biomarkers, and novel approaches are required for the detection and treatment of SS. Exosomes represent an emerging field in the discovery of biomarkers and the management of SS. Exosomes, a subtype of extracellular vesicles, are secreted by various cell types and can be found in most bodily fluids. Exosomes are packed with cytokines and other proteins, bioactive lipids, and nucleic acids (mRNA, circular RNA, non-coding RNA, tRNA, microRNA, genomic DNA, and ssDNA), and transport such cargo between cells. Evidence has indicated that exosomes may play roles in processes such as the modulation of the immune response and activation of inflammation. Moreover, due to features such as stability, low immunogenicity and toxicity, long half-life, and the capacity to penetrate the blood-brain barrier, exosomes have also emerged as therapeutic tools for SS. In this review, we summarize existing literature regarding the biogenesis, isolation, and function of exosomes, specifically focusing on exosomes as novel biomarkers and their potential therapeutic uses in SS.
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Affiliation(s)
- Yupeng Huang
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China
| | - Ruicen Li
- Health Management Center, West China Hospital, Sichuan University, Chengdu, China
| | - Sheng Ye
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China
| | - Sang Lin
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China
| | - Geng Yin
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China
| | - Qibing Xie
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China
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Zhang W, Liu Y, Jiang J, Tang Y, Tang Y, Liang X. Extracellular vesicle long non-coding RNA-mediated crosstalk in the tumor microenvironment: Tiny molecules, huge roles. Cancer Sci 2020; 111:2726-2735. [PMID: 32437078 PMCID: PMC7419043 DOI: 10.1111/cas.14494] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 05/12/2020] [Accepted: 05/15/2020] [Indexed: 02/05/2023] Open
Abstract
Emerging evidence has shown that dynamic crosstalk among cells in the tumor microenvironment modulates the progression and chemotherapeutic responses of cancer. Extracellular vesicles comprise a crucial form of intracellular communication through horizontal transfer of bioactive molecules, including long non-coding RNA (lncRNA), to neighboring cells. Three main types of extracellular vesicles are exosomes, microvesicles and apoptotic bodies, exhibiting a wide range of sizes and different biogenesis. Over the last decade, dysregulation of extracellular vesicle lncRNA has been revealed to remodel the tumor microenvironment and induce aggressive phenotypes of tumor cells, thereby facilitating tumor growth and development. This review will focus on extracellular vesicle lncRNA-mediated crosstalk between tumor cells and recipient cells, including tumor cells as well as stromal cells in the tumor microenvironment, and overview the mechanisms by which lncRNA are selectively sorted into extracellular vesicles, which may pave the way for their clinical application in cancer diagnosis and treatment.
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Affiliation(s)
- Wei‐long Zhang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengduChina
| | - Yan Liu
- Affiliated Hospital of North Sichuan Medical CollegeNanchongChina
| | - Jian Jiang
- Department of Head and Neck SurgerySichuan Cancer Hospital & Institute, Sichuan Cancer CenterSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduChina
| | - Ya‐Jie Tang
- State Key Laboratory of Microbial TechnologyShandong UniversityQingdaoChina
| | - Ya‐ling Tang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengduChina
| | - Xin‐hua Liang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengduChina
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Liu S, Xu X, Liang S, Chen Z, Zhang Y, Qian A, Hu L. The Application of MSCs-Derived Extracellular Vesicles in Bone Disorders: Novel Cell-Free Therapeutic Strategy. Front Cell Dev Biol 2020; 8:619. [PMID: 32793590 PMCID: PMC7387669 DOI: 10.3389/fcell.2020.00619] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Accepted: 06/22/2020] [Indexed: 12/11/2022] Open
Abstract
Bone is crucial for supporting the body, protecting other organs, providing minerals, and secreting hormone to regulate other organ's function. Bone disorders result in pain and disability, severely affecting human health, reducing the quality of life and increasing costs to society. With the rapid increase in the aging population worldwide, bone disorders have become one major disease. As a result, efficacious therapies of bone disorders have become the focus of attention worldwide. Mesenchymal stem cells (MSCs) have been widely explored as a new therapeutic method for numerous diseases. Recent evidence suggests that the therapeutic effects of MSCs are mainly mediated by their extracellular vesicles (EV). MSCs-derived extracellular vesicles (MSCs-EV) is indicated as a novel cell-free alternative to cell therapy with MSCs in regenerative medicine. Here, we review the current knowledge of EV and highlight the application studies of MSCs-EV in bone disorders by focusing on osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis (OP), and bone fracture. Moreover, we discuss the key issues and perspectives of MSCs-EV as a clinical therapeutic strategy for bone diseases.
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Affiliation(s)
- Shuyu Liu
- Laboratary for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- Xi’an Key Laboratory of Special Medicine and Health Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
| | - Xia Xu
- Laboratary for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- Xi’an Key Laboratory of Special Medicine and Health Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
| | - Shujing Liang
- Laboratary for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- Xi’an Key Laboratory of Special Medicine and Health Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
| | - Zhihao Chen
- Laboratary for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- Xi’an Key Laboratory of Special Medicine and Health Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
| | - Yan Zhang
- Laboratary for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- Xi’an Key Laboratory of Special Medicine and Health Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
| | - Airong Qian
- Laboratary for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- Xi’an Key Laboratory of Special Medicine and Health Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
| | - Lifang Hu
- Laboratary for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- Xi’an Key Laboratory of Special Medicine and Health Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
- NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China
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44
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Zhang S, Hou Y, Yang J, Xie D, Jiang L, Hu H, Hu J, Luo C, Zhang Q. Application of mesenchymal stem cell exosomes and their drug-loading systems in acute liver failure. J Cell Mol Med 2020; 24:7082-7093. [PMID: 32492261 PMCID: PMC7339207 DOI: 10.1111/jcmm.15290] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 03/22/2020] [Accepted: 03/26/2020] [Indexed: 12/11/2022] Open
Abstract
Stem cell exosomes are nanoscale membrane vesicles released from stem cells of various origins that can regulate signal transduction pathways between liver cells, and their functions in intercellular communication have been recognized. Due to their natural substance transport properties and excellent biocompatibility, exosomes can also be used as drug carriers to release a variety of substances, which has great prospects in the treatment of critical and incurable diseases. Different types of stem cell exosomes have been used to study liver diseases. Due to current difficulties in the treatment of acute liver failure (ALF), this review will outline the potential of stem cell exosomes for ALF treatment. Specifically, we reviewed the pathogenesis of acute liver failure and the latest progress in the use of stem cell exosomes in the treatment of ALF, including the role of exosomes in inhibiting the ALF inflammatory response and regulating signal transduction pathways, the advantages of stem cell exosomes and their use as a drug‐loading system, and their pre‐clinical application in the treatment of ALF. Finally, the clinical research status of stem cell therapy for ALF and the current challenges of exosome clinical transformation are summarized.
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Affiliation(s)
- Shuqin Zhang
- Office of Clinical Trial of Drug, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Yu Hou
- Office of Clinical Trial of Drug, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Jing Yang
- Office of Clinical Trial of Drug, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Denghui Xie
- Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Linrui Jiang
- Office of Clinical Trial of Drug, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Huazhong Hu
- Office of Clinical Trial of Drug, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Jingjing Hu
- Office of Clinical Trial of Drug, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Caizhu Luo
- Office of Clinical Trial of Drug, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Qun Zhang
- Office of Clinical Trial of Drug, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
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45
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D’Agnelli S, Gerra MC, Bignami E, Arendt-Nielsen L. Exosomes as a new pain biomarker opportunity. Mol Pain 2020; 16:1744806920957800. [PMID: 32909507 PMCID: PMC7493250 DOI: 10.1177/1744806920957800] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 07/08/2020] [Accepted: 07/16/2020] [Indexed: 12/15/2022] Open
Abstract
Exosomes are extracellular microvesicles implicated in intercellular communication with ability to transfer cargo molecules, including protein, lipids, and nucleic acids, at both close and distant target sites. It has been shown that exosomes are implicated in physiological and pathological processes. In recent years, the interest on exosomes' role in many pain states has increased. Their involvements in pain processes have been demonstrated by studies on different chronic pain diseases, both inflammatory and neuropathic, such as osteoarthritis, rheumatoid arthritis, inflammatory bowel diseases, neurodegenerative pathologies, complex regional pain syndrome, and peripheral nerve injury. Animal and clinical studies investigated exosomes-based treatments, showing their ability to improve painful symptoms with fewer side effects, with potential immunoprotective and anti-inflammatory effect. Specific molecular patterns characterize exosomes' cargo according to the cellular origin, epigenetic modifications, environmental state, and stressor factors. Therefore, the identification of specific cargo's profile associated to pain states may lead to recognize specific pathological states and to consider the use of exosomes as biomarkers of diseases. Furthermore, exosomes' ability to transfer information and their presence in many accessible biological fluids suggest a potential use as novel non-invasive therapeutic tools in pain field.
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Affiliation(s)
- Simona D’Agnelli
- Anesthesiology, Critical Care and Pain Medicine Division, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Maria C Gerra
- Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
| | - Elena Bignami
- Anesthesiology, Critical Care and Pain Medicine Division, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Lars Arendt-Nielsen
- Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
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46
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Ramasubramanian L, Kumar P, Wang A. Engineering Extracellular Vesicles as Nanotherapeutics for Regenerative Medicine. Biomolecules 2019; 10:48. [PMID: 31905611 PMCID: PMC7023093 DOI: 10.3390/biom10010048] [Citation(s) in RCA: 75] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 12/24/2019] [Accepted: 12/26/2019] [Indexed: 01/01/2023] Open
Abstract
Long thought of to be vesicles that primarily recycled waste biomolecules from cells, extracellular vesicles (EVs) have now emerged as a new class of nanotherapeutics for regenerative medicine. Recent studies have proven their potential as mediators of cell proliferation, immunomodulation, extracellular matrix organization and angiogenesis, and are currently being used as treatments for a variety of diseases and injuries. They are now being used in combination with a variety of more traditional biomaterials and tissue engineering strategies to stimulate tissue repair and wound healing. However, the clinical translation of EVs has been greatly slowed due to difficulties in EV isolation and purification, as well as their limited yields and functional heterogeneity. Thus, a field of EV engineering has emerged in order to augment the natural properties of EVs and to recapitulate their function in semi-synthetic and synthetic EVs. Here, we have reviewed current technologies and techniques in this growing field of EV engineering while highlighting possible future applications for regenerative medicine.
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Affiliation(s)
- Lalithasri Ramasubramanian
- Surgical Bioengineering Laboratory, Department of Surgery, School of Medicine, University of California–Davis, Sacramento, CA 95817, USA (P.K.)
- Department of Biomedical Engineering, University of California–Davis, Davis, CA 95616, USA
| | - Priyadarsini Kumar
- Surgical Bioengineering Laboratory, Department of Surgery, School of Medicine, University of California–Davis, Sacramento, CA 95817, USA (P.K.)
- Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children–Northern California, Sacramento, CA 95817, USA
| | - Aijun Wang
- Surgical Bioengineering Laboratory, Department of Surgery, School of Medicine, University of California–Davis, Sacramento, CA 95817, USA (P.K.)
- Department of Biomedical Engineering, University of California–Davis, Davis, CA 95616, USA
- Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children–Northern California, Sacramento, CA 95817, USA
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47
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Li N, Zhao L, Wei Y, Ea VL, Nian H, Wei R. Recent advances of exosomes in immune-mediated eye diseases. Stem Cell Res Ther 2019; 10:278. [PMID: 31470892 PMCID: PMC6716826 DOI: 10.1186/s13287-019-1372-0] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Exosomes, nanosized extracellular vesicles of 30-150 nm, are shed by almost all cell types. Bearing proteins, lipids, RNAs, and DNAs, exosomes have emerged as vital biological mediators in cell-to-cell communication, affecting a plethora of physiological and pathological processes. Particularly, mounting evidence indicates that immunologically active exosomes can regulate both innate and adaptive immune responses. Herein, we review recent advances in the research of exosomes in several immune-mediated eye diseases, including Sjögren's syndrome (SS) dry eye, corneal allograft rejection, autoimmune uveitis, and age-related macular degeneration (AMD). Additionally, we discuss the potential of exosomes as novel biomarkers and drug delivery vesicles for the diagnosis and treatment of eye diseases.
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Affiliation(s)
- Na Li
- Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, No.251 Fukang Road, Nankai District, Tianjin, 300384, People's Republic of China
| | - Lu Zhao
- Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, No.251 Fukang Road, Nankai District, Tianjin, 300384, People's Republic of China
| | - Yankai Wei
- Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, No.251 Fukang Road, Nankai District, Tianjin, 300384, People's Republic of China
| | - Vicki L Ea
- Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, No.251 Fukang Road, Nankai District, Tianjin, 300384, People's Republic of China
| | - Hong Nian
- Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, No.251 Fukang Road, Nankai District, Tianjin, 300384, People's Republic of China.
| | - Ruihua Wei
- Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, No.251 Fukang Road, Nankai District, Tianjin, 300384, People's Republic of China.
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48
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Delivery of microRNAs by Extracellular Vesicles in Viral Infections: Could the News be Packaged? Cells 2019; 8:cells8060611. [PMID: 31216738 PMCID: PMC6627707 DOI: 10.3390/cells8060611] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 06/04/2019] [Accepted: 06/13/2019] [Indexed: 12/18/2022] Open
Abstract
Extracellular vesicles (EVs) are released by various cells and recently have attracted attention because they constitute a refined system of cell-cell communication. EVs deliver a diverse array of biomolecules including messenger RNAs (mRNAs), microRNAs (miRNAs), proteins and lipids, and they can be used as potential biomarkers in normal and pathological conditions. The cargo of EVs is a snapshot of the donor cell profile; thus, in viral infections, EVs produced by infected cells could be a central player in disease pathogenesis. In this context, miRNAs incorporated into EVs can affect the immune recognition of viruses and promote or restrict their replication in target cells. In this review, we provide an updated overview of the roles played by EV-delivered miRNAs in viral infections and discuss the potential consequences for the host response. The full understanding of the functions of EVs and miRNAs can turn into useful biomarkers for infection detection and monitoring and/or uncover potential therapeutic targets.
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49
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Tai YL, Chu PY, Lee BH, Chen KC, Yang CY, Kuo WH, Shen TL. Basics and applications of tumor-derived extracellular vesicles. J Biomed Sci 2019; 26:35. [PMID: 31078138 PMCID: PMC6511661 DOI: 10.1186/s12929-019-0533-x] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 05/07/2019] [Indexed: 02/07/2023] Open
Abstract
Extracellular vesicle (EV)-mediated intercellular communication acts as a critical culprit in cancer development. The selective packaging of oncogenic molecules renders tumor-derived EVs capable of altering the tumor microenvironment and thereby modulating cancer developments that may contribute to drug resistance and cancer recurrence. Moreover, the molecular and functional characteristics of cancer through its development and posttreatment evolve over time. Tumor-derived EVs are profoundly involved in this process and can, therefore, provide valuable real-time information to reflect dynamic changes occurring within the body. Because they bear unique molecular profiles or signatures, tumor-derived EVs have been highlighted as valuable diagnostic and predictive biomarkers as well as novel therapeutic targets. In addition, the use of an advanced EV-based drug delivery system for cancer therapeutics has recently been emphasized in both basic and clinical studies. In this review, we highlight comprehensive aspects of tumor-derived EVs in oncogenic processes and their potential clinical applications.
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Affiliation(s)
- Yu-Ling Tai
- Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, Taiwan.,Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Pei-Yu Chu
- Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, Taiwan
| | - Bao-Hong Lee
- Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Ko-Chien Chen
- Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, Taiwan
| | - Chia-Yu Yang
- Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, Taiwan
| | - Wen-Hung Kuo
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Tang-Long Shen
- Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, Taiwan. .,Center for Biotechnology, National Taiwan University, Taipei, Taiwan.
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50
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Qin S, Dorschner RA, Masini I, Lavoie-Gagne O, Stahl PD, Costantini TW, Baird A, Eliceiri BP. TBC1D3 regulates the payload and biological activity of extracellular vesicles that mediate tissue repair. FASEB J 2019; 33:6129-6139. [PMID: 30715917 PMCID: PMC6463925 DOI: 10.1096/fj.201802388r] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Accepted: 01/07/2019] [Indexed: 12/16/2022]
Abstract
Healthy repair of cutaneous injury is a coordinated response of inflammatory cells, secreted factors, and biologically active extracellular vesicles (EVs). Although constitutive release of EVs into biologic fluids is a hallmark of cultured cells and tumors, their payload and biologic activity appears to be tightly regulated. We show that Tre-2/Bub2/Cdc16 (TBC1) domain family member 3 (TBC1D3) drives the release of an EV population that causes a decrease in phosphorylation of the transcription factor signal transducer and activator of transcription 3 in naive recipient cells. To explore the biologic activity of EVs in vivo, we used a mouse model of sterile subcutaneous inflammation to determine the payload and biologic activity of EVs released into the microenvironment by committed myeloid lineages and stroma. Expression of TBC1D3 in macrophages altered the payload of their released EVs, including RNA-binding proteins, molecular motors, and proteins regulating secretory pathways. A wound-healing model demonstrated that closure was delayed by EVs released under the control of TBC1D3. We show that modulating the secretory repertoire of a cell regulates EV payload and biologic activity that affects outcomes in tissue repair and establishes a strategy for modifying EVs mediating specific biologic responses.-Qin, S., Dorschner, R. A., Masini, I., Lavoie-Gagne, O., Stahl, P. D., Costantini, T. W., Baird, A., Eliceiri, B. P. TBC1D3 regulates the payload and biological activity of extracellular vesicles that mediate tissue repair.
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Affiliation(s)
- Shu Qin
- Department of Surgery, University of California–San Diego, La Jolla, California, USA
- Department of Plastic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China; and
| | - Robert A. Dorschner
- Department of Surgery, University of California–San Diego, La Jolla, California, USA
| | - Irene Masini
- Department of Surgery, University of California–San Diego, La Jolla, California, USA
| | - Ophelia Lavoie-Gagne
- Department of Surgery, University of California–San Diego, La Jolla, California, USA
| | - Philip D. Stahl
- Department of Cell Biology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Todd W. Costantini
- Department of Surgery, University of California–San Diego, La Jolla, California, USA
| | - Andrew Baird
- Department of Surgery, University of California–San Diego, La Jolla, California, USA
| | - Brian P. Eliceiri
- Department of Surgery, University of California–San Diego, La Jolla, California, USA
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