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Avalos-de Leon CG, Thomson AW. Regulatory Immune Cell-derived Exosomes: Modes of Action and Therapeutic Potential in Transplantation. Transplantation 2025; 109:1124-1137. [PMID: 39865513 PMCID: PMC12187562 DOI: 10.1097/tp.0000000000005309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2025]
Abstract
Reduced dependence on antirejection agents, improved long-term allograft survival, and induction of operational tolerance remain major unmet needs in organ transplantation due to the limitations of current immunosuppressive therapies. To address this challenge, investigators are exploring the therapeutic potential of adoptively transferred host- or donor-derived regulatory immune cells. Extracellular vesicles of endosomal origin (exosomes) secreted by these cells seem to be important contributors to their immunoregulatory properties. Twenty years ago, it was first reported that donor-derived exosomes could extend the survival of transplanted organs in rodents. Recent studies have revealed that regulatory immune cells, such as regulatory myeloid cells (dendritic cells, macrophages, or myeloid-derived suppressor cells), regulatory T cells, or mesenchymal stem/stromal cells can suppress graft rejection via exosomes that express a cargo of immunosuppressive molecules. These include cell surface molecules that interact with adaptive immune cell receptors, immunoregulatory enzymes, and micro- and long noncoding RNAs that can regulate inflammatory gene expression via posttranscriptional changes and promote tolerance through promotion of regulatory T cells. This overview analyzes the diverse molecules and mechanisms that enable regulatory immune cell-derived exosomes to modulate alloimmunity and promote experimental transplant tolerance. We also discuss the potential benefits and limitations of their application as therapeutic entities in organ transplantation.
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Affiliation(s)
| | - Angus W. Thomson
- Starzl Transplantation Institute, Department of Surgery, Pittsburgh PA, USA
- Department of Immunology, University of Pittsburgh School of medicine, Pittsburgh PA, USA
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Yan X, Guo YX, Liu YX, Liu C. Mesenchymal stem cell-derived exosomes and the Wnt/β-catenin pathway: Unifying mechanisms of multi-organ regeneration and the path to precision clinical translation. World J Stem Cells 2025; 17:106902. [DOI: 10.4252/wjsc.v17.i6.106902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Revised: 03/31/2025] [Accepted: 05/08/2025] [Indexed: 06/25/2025] Open
Abstract
In this editorial, we discuss the article by Fu Y et al, indicating that hair development is influenced by exosomes from human adipose-derived stem/stromal cell-mediated cell-to-cell communication via the Wnt/β-catenin pathway. In recent years, mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exos) have emerged as a promising cell-free therapeutic strategy due to their robust regenerative capabilities across multiple tissues. MSC-Exos are enriched with bioactive molecules, including proteins, microRNAs, and growth factors, which activate critical signaling pathways, notably the Wnt/β-catenin pathway, to promote cell proliferation, differentiation, and tissue repair. This editorial systematically examines the application of MSC-Exos in regenerating diverse tissues such as hair follicles and kidney, lung, and cardiac muscle tissue. Central to their mechanism is the activation of the Wnt/β-catenin pathway, which drives cell cycle progression (via cyclin B1/cyclin-dependent kinase 1), suppresses apoptosis (through Bcl-2/Bax modulation), and attenuates fibrosis (by inhibiting transforming growth factor-β/alpha-smooth muscle actin). The challenges related to the clinical translation of exosome-based therapies, including standardization of isolation protocols, optimization of dosing and delivery methods, and safety evaluation, are discussed. The most important challenge is standardizing isolation protocols because exosomes obtained from different sources or treatment methods are different, which leads to differences in the therapeutic effects of exosomes. Overall, MSC-Exos provide an effective cell-free strategy for tissue repair and offer a robust foundation to develop personalized regenerative medicine.
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Affiliation(s)
- Xiong Yan
- The First Clinical Medical School, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Ya-Xiong Guo
- Surgical Unit 1, Shanxi Combined Traditional Chinese and Western Medicine Hospital, Taiyuan 030072, Shanxi Province, China
| | - Yu-Xiang Liu
- Department of Nephrology, Shanxi Provincial People’s Hospital, Taiyuan 030012, Shanxi Province, China
| | - Chun Liu
- The First Clinical Medical School, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
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Carrera-Bravo C, Zhou T, Chu T, Hang JW, Modh H, Huang C, Zhang S, Hao H, Cabada-García MJ, Malleret B, Wacker MG, Wang JW, Rénia L, Tan KSW. Chloroquine induces eryptosis in P. falciparum-infected red blood cells and the release of extracellular vesicles with a unique protein profile. Front Cell Infect Microbiol 2025; 15:1553123. [PMID: 40491429 PMCID: PMC12146344 DOI: 10.3389/fcimb.2025.1553123] [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: 12/30/2024] [Accepted: 04/30/2025] [Indexed: 06/11/2025] Open
Abstract
Introduction Malaria is a vector-borne parasitic disease that affects millions worldwide. To achieve the objective set by the World Health Organization of reducing malaria cases by 2030, antimalarial drugs with novel modes of action are required. Previously, a novel mechanism of action of chloroquine (CQ) was reported involving features of programmed cell death in the parasite, mainly characterized by calcium efflux from digestive vacuole permeabilization. Increased intracellular calcium induces suicidal death of erythrocytes, a process known as eryptosis. This study aimed to identify the hallmarks of eryptosis due to calcium redistribution and examine the downstream cellular effects during CQ treatment in infected red blood cells (iRBCs). Methods Synchronized Plasmodium falciparum 3D7 cultures at mid-late trophozoites were treated with CQ and other antimalarial compounds for 10 hours. Eryptotic markers, including phosphatidylserine (PS) exposure, cell shrinkage and membrane blebbing, were assessed by flow cytometry, scanning electron microscopy and western blot, respectively. Extracellular vesicles (EVs) were isolated from 3D7 malaria culture supernatants using differential ultracentrifugation, followed by their physical and proteomic characterization. THP-1-derived macrophages were stimulated with EVs to determine parasite-host interactions, as indicated by cytokine levels and transcriptomic analysis. Results Increased PS exposure, cell shrinkage, and membrane blebbing were observed, delineating an eryptotic phenotype in the host RBCs. Notably, the outward budding and blebbing of the iRBC plasma membrane led to the formation of EVs, which are complex structures with unique functional properties. Proteomic characterization of EVs from CQ-treated iRBCs revealed a high enrichment of proteasome and ribosome protein clusters. This unique EV cargo did not influence the parasite growth rate but might activate IFN signaling pathways mediated by IL-6 in THP-1-derived macrophages. Conclusion These findings provide new insights into a novel drug-induced cell death mechanism that targets the parasite and specific components of the infected host RBC.
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Affiliation(s)
- Claudia Carrera-Bravo
- Department of Microbiology and Immunology, Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- ASTAR Infectious Diseases Labs, Agency for Science, Technology and Research, Singapore, Singapore
| | - Tianchi Zhou
- Centre for Inflammation Research, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom
- Medical Research Council (MRC) Human Genetics Unit, Institute of Genetics and Cancer, The University of Edinburg, Edinburgh, United Kingdom
| | - Trang Chu
- Department of Microbiology and Immunology, Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jing Wen Hang
- Department of Microbiology and Immunology, Immunology Translational Research Programme, Yoon Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Harshvardhan Modh
- Department of Pharmacy and Pharmaceutical Sciences, Faculty of Science, National University of Singapore, Singapore, Singapore
| | - Chenyuan Huang
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Nanomedicine Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Sitong Zhang
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Nanomedicine Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Haining Hao
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Nanomedicine Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Laboratory of Quality and Safety Risk Assessment for Agro-Products of the Ministry of Agriculture (Jinan), Institute of Quality Standard and Testing Technology for Agro-Products, Shandong Academy of Agricultural Sciences, Jinan, China
| | | | - Benoit Malleret
- Department of Microbiology and Immunology, Immunology Translational Research Programme, Yoon Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore
| | - Matthias G. Wacker
- Department of Pharmacy and Pharmaceutical Sciences, Faculty of Science, National University of Singapore, Singapore, Singapore
| | - Jiong-Wei Wang
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Nanomedicine Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Cardiovascular Research Institute (CVRI), National University Health System, Singapore, Singapore
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Laurent Rénia
- ASTAR Infectious Diseases Labs, Agency for Science, Technology and Research, Singapore, Singapore
| | - Kevin S. W. Tan
- Department of Microbiology and Immunology, Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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Cui L, Song Y, Hou Z, Yang L, Guo S, Wang C. From bench to bedside: the research status and application opportunity of extracellular vesicles and their engineering strategies in the treatment of skin defects. J Nanobiotechnology 2025; 23:375. [PMID: 40414838 DOI: 10.1186/s12951-025-03461-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 05/11/2025] [Indexed: 05/27/2025] Open
Abstract
Engineered extracellular vesicles (EVs), which are EVs modified to enhance certain biological properties, offer a promising therapeutic strategy for the treatment of skin defects. Conventional nanomaterials often encounter clinical translation challenges due to potential toxicity and limited targeting. Engineered EVs, utilizing inherent biocompatibility and effective physiological barrier traversal, can ameliorate the limitations of conventional EV therapies to some extent, including detection, isolation, purification, and therapeutic validation. Recent advances in EV engineering, such as genetic modification of production cells to control cargo, surface engineering for targeted delivery, and pre-treatment of parental cells to optimize production and bioactivity, have improved therapeutic efficacy in laboratory studies through enhanced targeting, prolonged retention time, and increased yield. Many studies have suggested the potential ability of engineered EVs to treat a variety of skin defects, including diabetic wounds, burns, and hypertrophic scars, providing a promising avenue for their clinical translation in this area. This paper reviews the therapeutic potential of engineered EVs in skin regeneration, highlighting their role in promoting cell migration and angiogenesis, modulating inflammation and reducing scar formation during wound healing. In addition, given the investment in this rapidly evolving field and the growing clinical trial activity, this review also explores recent global advances and provides an outlook on future application opportunities for EVs in the treatment of skin defects.
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Affiliation(s)
- Longwei Cui
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, 110002, People's Republic of China
| | - Yantao Song
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, 110002, People's Republic of China
| | - Zhipeng Hou
- Research Center for Biomedical Materials, Shenyang Key Laboratory of Biomedical Polymers, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People's Republic of China
| | - Liqun Yang
- Research Center for Biomedical Materials, Shenyang Key Laboratory of Biomedical Polymers, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People's Republic of China.
| | - Shu Guo
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, 110002, People's Republic of China.
| | - Chenchao Wang
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, 110002, People's Republic of China.
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Tu C, Gao X, Zheng H, Huang R, Yang F, Dong Y, Jing K, Groth T, Zhao M. Innovative injectable, self-healing, exosome cross-linked biomimetic hydrogel for cartilage regeneration. J Control Release 2025; 381:113608. [PMID: 40054632 DOI: 10.1016/j.jconrel.2025.113608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2025] [Revised: 03/01/2025] [Accepted: 03/04/2025] [Indexed: 03/28/2025]
Abstract
The limited self-healing capacity of cartilage hinders its repair and regeneration at the defect sites. Recent research into small-molecular compounds has shown promise in achieving a better regeneration of cartilage. In this study, we encapsulate kartogenin (KGN) and transforming growth factor β1 (TGF-β1) within mesenchymal stem cells derived exosomes (EKT), and then coated them with succinylated chitosan (sCH) to create positively charged exosomes, termed CEKT. These CEKT exhibit exceptional chondrogenic promoting capabilities shown during in vitro studies with bone marrow derived mesenchymal stem cells (BMSCs). They also can penetrate deep into cartilage tissue derived from porcine knee joints guided by their positive charge. Subsequently, a dynamic exosomes-crosslinked hydrogel (Gel-CEKT) is fabricated by crosslinking CEKT with oxidized chondroitin sulfate (oCS) and Wharton's jelly (WJ) through imine bond formation. Physicochemical studies revealed the injectability, excellent adhesive, and self-healing abilities of this hydrogel, which enables minimally invasive and precise treatment of cartilage defects, assisted by the enriched and sustained administration of CEKT. In vitro cell experiments show that Gel-CEKT can efficiently recruit BMSCs and significantly promote the gene expression of Sox9 and protein expression of collagen II and aggrecan. Furthermore, we show in a rat model of cartilage defect that the Gel-CEKT demonstrates superior performance compared to Gel@EKT, which has freely encapsulated exosomes in the hydrogel. The freely encapsulated exosomes are rapidly released, whereas the exosome-crosslinked gel structure ensures sustained retention and functionality at the site of defect. This leads to impressive outcomings, including extensive new cartilage tissue formation, a smoother cartilage surface, significant chondrocyte production, and seamless integration with orderly and continuous structure formation between cartilage and subchondral bone. This study underscores the potential of exosomes-crosslinked hydrogels as a novel and promising therapeutic approach for clinical cartilage regeneration.
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Affiliation(s)
- Chenlin Tu
- Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; Orthopedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China
| | - Xiang Gao
- Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; Orthopedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China
| | - Hong Zheng
- Orthopedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China
| | - Rui Huang
- Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China
| | - Fengkai Yang
- Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; Orthopedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China
| | - Yeying Dong
- Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; Orthopedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China
| | - Kaipeng Jing
- Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Zhanjiang 524001, China
| | - Thomas Groth
- Department Biomedical Materials, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, 0699 Halle (Saale), Germany
| | - Mingyan Zhao
- Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China; Orthopedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
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Poondla N, Babaeizad A, Sheykhhasan M, Barry CJ, Manoochehri H, Tanzadehpanah H, Mahaki H, Al-Musawi S. Exosome-based therapies and biomarkers in stroke: Current advances and future directions. Exp Neurol 2025; 391:115286. [PMID: 40328416 DOI: 10.1016/j.expneurol.2025.115286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 04/22/2025] [Accepted: 04/29/2025] [Indexed: 05/08/2025]
Abstract
Stroke is a challenging neurological condition caused by interrupted blood flow to the brain and presents substantial global health concerns due to its prevalence and limited treatment options. Exosomes, tiny vesicles released by cells, are gaining attention for their potential in targeted drug delivery and as diagnostic and therapeutic biomarkers for stroke. This article outlines recent advances in exosome-based drug delivery systems and examines their application in managing stroke. Stroke presents with diverse symptoms depending on the brain region affected, and current treatments primarily aim to restore blood flow and manage risk factors. Exosomes exhibit a unique structure and composition and contain bioactive molecules. Their ability to cross the blood-brain barrier and target specific cells makes them promising candidates for precise drug delivery in stroke therapy. Exosomes contribute extensively to stroke pathophysiology and present considerable therapeutic promise by promoting neuroprotection and assisting in brain repair mechanisms. They can be engineered to carry various therapeutic substances, such as small molecules, enabling highly specific targeted delivery. Furthermore, the molecular compositions of exosomes reflect the pathological changes observed in stroke, indicating their potential use as biomarkers for early diagnosis, monitoring of disease progression, and creating individualized treatment strategies. Despite promising developments, challenges remain in optimizing exosome production, purification, and cargo loading. Further investigations into their biological mechanisms and clinical validation are crucial for translating their potential into tangible benefits for patients. This article highlights recent advances and future prospects in exosome research, underscoring their application as novel diagnostic and therapeutic tools in stroke management.
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Affiliation(s)
- Naresh Poondla
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Center for Global Health Research, Saveetha Medical College& Hospital, Chennai 602105, India
| | - Ali Babaeizad
- Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Mohsen Sheykhhasan
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.
| | | | - Hamed Manoochehri
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Hamid Tanzadehpanah
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hanie Mahaki
- Vascular & Endovascular Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Feng P, Zhang X, Gao J, Jiang L, Li Y. The Roles of Exosomes in Anti-Cancer Drugs. Cancer Med 2025; 14:e70897. [PMID: 40298189 PMCID: PMC12038748 DOI: 10.1002/cam4.70897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 04/03/2025] [Accepted: 04/09/2025] [Indexed: 04/30/2025] Open
Abstract
BACKGROUND Cancer is an escalating global health issue, with rising incidence rates annually. Chemotherapy, a primary cancer treatment, often exhibits low tumor-targeting efficiency and severe side effects, limiting its effectiveness. Recent research indicates that exosomes, due to their immunogenicity and molecular delivery capabilities, hold significant potential as drug carriers for tumor treatment. METHODS This review summarizes the current status, powerful therapeutic potential, and challenges of using exosomes for the treatment of tumors. RESULTS Exosomes are crucial in tumor diagnosis, onset, and progression. To improve the efficacy of exosome-based treatments, researchers are exploring various biological, physical, and chemical approaches to engineer exosomes as a new nanomedicine translational therapy platform with broad and alterable therapeutic capabilities. Numerous clinical trials are currently underway investigating the safety and tolerability of exosomes carrying drugs to specific sites for the treatment of tumors. CONCLUSIONS Exosomes can be engineered as carriers to deliver therapeutic molecules to specific cells and tissues, offering a novel approach for disease treatment.
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Affiliation(s)
- Panpan Feng
- Department of RadiotherapyThe First Affiliated Hospital of Jinzhou Medical UniversityJinzhouChina
| | - Xiaodong Zhang
- Department of General SurgeryBeijing Friendship Hospital, Capital Medical UniversityBeijingChina
| | - Jian Gao
- Science Experiment Center of China Medical UniversityShenyangChina
| | - Lei Jiang
- Department of General SurgeryThe First Affiliated Hospital of Jinzhou Medical UniversityJinzhouChina
| | - Yan Li
- Department of RadiotherapyThe First Affiliated Hospital of Jinzhou Medical UniversityJinzhouChina
- Liaoning Provincial Key Laboratory of Clinical Oncology MetabonomicsThe First Affiliated Hospital of Jinzhou Medical UniversityJinzhouChina
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Zhou X, Huang J, Zhang D, Qian Z, Zuo X, Sun Y. Small extracellular vesicles: the origins, current status, future prospects, and applications. Stem Cell Res Ther 2025; 16:184. [PMID: 40247402 PMCID: PMC12004682 DOI: 10.1186/s13287-025-04330-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2025] [Accepted: 04/09/2025] [Indexed: 04/19/2025] Open
Abstract
Small extracellular vesicles (sEVs) are membrane-bound vesicles with a size of less than 200 nm, released by cells. Due to their relatively small molecular weight and ability to participate in intercellular communication, sEVs can serve not only as carriers of biomarkers for disease diagnosis but also as effective drug delivery agents. Furthermore, these vesicles are involved in regulating the onset and progression of various diseases, reflecting the physiological and functional states of cells. This paper introduces the classification of extracellular vesicles, with a focus on the extraction and identification of sEVs and their significant role in repair, diagnosis, and intercellular communication. Additionally, the paper addresses the engineering modification of sEVs to provide a reference for enhanced understanding and application.
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Affiliation(s)
- Xinyi Zhou
- Department of Clinical Laboratory, the Affiliated Yixing Hospital of Jiangsu University, Yixing, China
| | - Jin Huang
- Department of Geriatrics, the Affiliated Yixing Hospital of Jiangsu University, Yixing, China
| | - Dianqi Zhang
- Department of Central Laboratory, the Affiliated Yixing Hospital of Jiangsu University, Yixing, China
| | - Zhenyu Qian
- Department of Neurology, the Affiliated Yixing Hospital of Jiangsu University, Yixing, China
| | - Xin Zuo
- Department of Geriatrics, the Affiliated Yixing Hospital of Jiangsu University, Yixing, China.
| | - Yaoxiang Sun
- Department of Clinical Laboratory, the Affiliated Yixing Hospital of Jiangsu University, Yixing, China.
- Department of Central Laboratory, the Affiliated Yixing Hospital of Jiangsu University, Yixing, China.
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Mivehchi H, Eskandari-Yaghbastlo A, Emrahoglu S, Saeidpour Masouleh S, Faghihinia F, Ayoubi S, Nabi Afjadi M. Tiny messengers, big Impact: Exosomes driving EMT in oral cancer. Pathol Res Pract 2025; 268:155873. [PMID: 40022766 DOI: 10.1016/j.prp.2025.155873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 02/13/2025] [Accepted: 02/26/2025] [Indexed: 03/04/2025]
Abstract
Exosomes are indispensable extracellular vesicles that facilitate intercellular communication and are crucial for both healthy and pathological conditions, including cancer. The capacity of exosomes to echo the molecular characteristics of their cells of origin, including malignant cells, makes them indispensable tools for diagnosing and tracking disease progression in the field of oncology. Oral squamous cell carcinoma (OSCC), which has been identified as the sixth most prevalent cancer worldwide, has been linked to numerous risk factors, including tobacco use, alcohol consumption, human papillomavirus (HPV) infection, and inadequate oral hygiene. Exosomes pointedly influence the advancement of oral cancer via promoting tumor cell growth, invasion, angiogenesis, and immune evasion through the alteration of the tumor microenvironment. A critical apparatus in cancer metastasis is the epithelial-to-mesenchymal transition (EMT), during which cancer cells acquire improved migratory and invasive properties. EMT plays a role in metastasis, resistance to treatment, and evasion of the immune response. Exosomes facilitate EMT in oral cancer by delivering bioactive molecules that influence EMT signaling pathways. These exosomes inspire EMT in recipient cells, by this means enhancing tumor invasion and metastasis. This study aims to identify the specific exosomal components and signaling pathways that are tangled in EMT, in that way providing new avenues for targeted therapies designed to hinder the metastasis of oral cancer.
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Affiliation(s)
- Hassan Mivehchi
- Faculty of Dentistry, University of Debrecen, Debrecen, Hungary
| | | | - Sahand Emrahoglu
- School of Dental Medicine, Case Western Reserve University, Cleveland, OH, USA
| | | | - Farbod Faghihinia
- School of Dentistry, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Saminalsadat Ayoubi
- School of Dental Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Mohsen Nabi Afjadi
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
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10
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Semeradtova A, Liegertova M, Herma R, Capkova M, Brignole C, Del Zotto G. Extracellular vesicles in cancer´s communication: messages we can read and how to answer. Mol Cancer 2025; 24:86. [PMID: 40108630 PMCID: PMC11921637 DOI: 10.1186/s12943-025-02282-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Accepted: 02/24/2025] [Indexed: 03/22/2025] Open
Abstract
Extracellular vesicles (EVs) are emerging as critical mediators of intercellular communication in the tumor microenvironment (TME), profoundly influencing cancer progression. These nano-sized vesicles, released by both tumor and stromal cells, carry a diverse cargo of proteins, nucleic acids, and lipids, reflecting the dynamic cellular landscape and mediating intricate interactions between cells. This review provides a comprehensive overview of the biogenesis, composition, and functional roles of EVs in cancer, highlighting their significance in both basic research and clinical applications. We discuss how cancer cells manipulate EV biogenesis pathways to produce vesicles enriched with pro-tumorigenic molecules, explore the specific contributions of EVs to key hallmarks of cancer, such as angiogenesis, metastasis, and immune evasion, emphasizing their role in shaping TME and driving therapeutic resistance. Concurrently, we submit recent knowledge on how the cargo of EVs can serve as a valuable source of biomarkers for minimally invasive liquid biopsies, and its therapeutic potential, particularly as targeted drug delivery vehicles and immunomodulatory agents, showcasing their promise for enhancing the efficacy and safety of cancer treatments. By deciphering the intricate messages carried by EVs, we can gain a deeper understanding of cancer biology and develop more effective strategies for early detection, targeted therapy, and immunotherapy, paving the way for a new era of personalized and precise cancer medicine with the potential to significantly improve patient outcomes.
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Affiliation(s)
- Alena Semeradtova
- Institute of Photonics and Electronics of the CAS, Chaberská 1014/57, Prague, 182 51, Czech Republic.
| | - Michaela Liegertova
- Centre for Nanomaterials and Biotechnology, Faculty of Science, Jan Evangelista Purkyně University in Ústí Nad Labem, Pasteurova 3632/15, Ústí Nad Labem, 40096, Czech Republic
| | - Regina Herma
- Centre for Nanomaterials and Biotechnology, Faculty of Science, Jan Evangelista Purkyně University in Ústí Nad Labem, Pasteurova 3632/15, Ústí Nad Labem, 40096, Czech Republic
| | - Magdalena Capkova
- Institute of Photonics and Electronics of the CAS, Chaberská 1014/57, Prague, 182 51, Czech Republic
| | - Chiara Brignole
- Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, Via G. Gaslini 5, 16147, Genoa, Italy.
| | - Genny Del Zotto
- Core Facilities, Department of Research and Diagnostics, IRCCS Istituto Giannina Gaslini, 16147, Genoa, Italy.
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11
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Wang F, Feng J, Jin A, Shao Y, Shen M, Ma J, Lei L, Liu L. Extracellular Vesicles for Disease Treatment. Int J Nanomedicine 2025; 20:3303-3337. [PMID: 40125438 PMCID: PMC11928757 DOI: 10.2147/ijn.s506456] [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: 11/14/2024] [Accepted: 02/20/2025] [Indexed: 03/25/2025] Open
Abstract
Traditional drug therapies suffer from problems such as easy drug degradation, side effects, and treatment resistance. Traditional disease diagnosis also suffers from high error rates and late diagnosis. Extracellular vesicles (EVs) are nanoscale spherical lipid bilayer vesicles secreted by cells that carry various biologically active components and are integral to intercellular communication. EVs can be found in different body fluids and may reflect the state of the parental cells, making them ideal noninvasive biomarkers for disease-specific diagnosis. The multifaceted characteristics of EVs render them optimal candidates for drug delivery vehicles, with evidence suggesting their efficacy in the treatment of various ailments. However, poor stability and easy degradation of natural EVs have affected their applications. To solve the problems of poor stability and easy degradation of natural EVs, they can be engineered and modified to obtain more stable and multifunctional EVs. In this study, we review the shortcomings of traditional drug delivery methods and describe how to modify EVs to form engineered EVs to improve their utilization. An innovative stimulus-responsive drug delivery system for EVs has also been proposed. We also summarize the current applications and research status of EVs in the diagnosis and treatment of different systemic diseases, and look forward to future research directions, providing research ideas for scholars.
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Affiliation(s)
- Fangyan Wang
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, 310015, People’s Republic of China
| | - Jiayin Feng
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, 310015, People’s Republic of China
| | - Anqi Jin
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, 310015, People’s Republic of China
| | - Yunyuan Shao
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, 310015, People’s Republic of China
| | - Mengen Shen
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, 310015, People’s Republic of China
| | - Jiaqi Ma
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, 310015, People’s Republic of China
| | - Lanjie Lei
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, 310015, People’s Republic of China
| | - Liangle Liu
- The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325200, People’s Republic of China
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12
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Su X, Wang H, Li Q, Chen Z. Extracellular Vesicles: A Review of Their Therapeutic Potentials, Sources, Biodistribution, and Administration Routes. Int J Nanomedicine 2025; 20:3175-3199. [PMID: 40098717 PMCID: PMC11913029 DOI: 10.2147/ijn.s502591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 02/18/2025] [Indexed: 03/19/2025] Open
Abstract
Extracellular vesicles (EVs) participate in intercellular communication and play an essential role in physiological and pathological processes. In recent years, EVs have garnered significant attention as cell-free therapeutic alternatives, vectors for drug and gene delivery, biomarkers for disease diagnosis and prognosis, vaccine development, and nutraceuticals. The biodistribution of EVs critically influences their efficacy and toxicity. Therefore, this review aims to discuss the main factors influencing the biodistribution of unmodified EVs, highlighting their distribution patterns, advantages, limitations, and applications under different routes of administration. In addition, we provide a comprehensive discussion of the currently available sources of EVs and summarize the current status of the therapeutic potentials of EVs. By optimizing administration routes and selecting appropriate EV sources, we aim to offer valuable insights to enhance the delivery efficiency and therapeutic efficacy of EVs to target tissues.
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Affiliation(s)
- Xiaorong Su
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China
| | - Hongxiang Wang
- Department of Hematology, Key Laboratory for Molecular Diagnosis of Hubei Province, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, People’s Republic of China
| | - Qiubai Li
- Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China
- Hubei Engineering Research Center for Application of Extracellular Vesicle, Hubei University of Science and Technology, Xianning, 437100, People’s Republic of China
| | - Zhichao Chen
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China
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13
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Zonouz AM, Rahbardar MG, Alibolandi M. Exosome-based platforms for treatment of multiple sclerosis. Brain Res Bull 2025; 222:111256. [PMID: 39952444 DOI: 10.1016/j.brainresbull.2025.111256] [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: 10/04/2024] [Revised: 01/18/2025] [Accepted: 02/10/2025] [Indexed: 02/17/2025]
Abstract
Multiple sclerosis (MS) is a chronic autoimmune illness characterized by inflammation and demyelination of the central nervous system (CNS). The effective delivery of therapeutic agents to the CNS continues to be an important barrier in MS treatment due to the blood-brain barrier and limited access to the affected areas. Exosome-based drug delivery systems have become an attractive option for targeted therapy in MS. Exosomes, small extracellular vesicles derived from various cell types, possess unique biological properties that make them ideal nanocarriers for delivering therapeutic cargo to specific cell populations in the CNS. In this study, we supply a comprehensive overview of the current advances and future perspectives of exosome-based drug delivery systems for MS. We discuss the biogenesis of exosomes, strategies for cargo loading, engineering approaches to enhance their targeting capabilities, and the potential clinical applications of exosome-mediated drug delivery in MS therapy. Additionally, we explore preclinical studies and animal models that demonstrate the effectiveness of exosome-based drug delivery in ameliorating MS pathology. By highlighting the challenges and opportunities in utilizing exosomes as drug delivery vehicles, this review aims to contribute to the growing body of knowledge in the field of nanomedicine for MS. Considering the potential of exosome-based drug delivery systems to enhance the accessibility, specificity, and effectiveness of therapies while minimizing off-target effects might change the therapeutic scenario for MS.
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Affiliation(s)
- Aidin Mohammadi Zonouz
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Mona Alibolandi
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
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14
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Zemanek T, Danisovic L, Nicodemou A. Exosomes and solid cancer therapy: where are we now? Med Oncol 2025; 42:77. [PMID: 39961904 PMCID: PMC11832697 DOI: 10.1007/s12032-025-02626-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Accepted: 02/11/2025] [Indexed: 02/20/2025]
Abstract
Cancer immunotherapy has revolutionized oncology, offering new hope for patients with previously incurable cancers. However, solid tumors remain a significant challenge due to immune evasion, therapeutic resistance, and the immunosuppressive tumor microenvironment. Exosomes, a specialized subset of extracellular vesicles, have emerged as promising tools in cancer therapy owing to their unique role in intercellular communication and immune modulation. These vesicles transport antigens, major histocompatibility complex (MHC) molecules, and immune-modulatory cargo, positioning them as potential platforms for cancer vaccines, drug delivery systems, and combinatorial therapies. Advances in engineered exosomes have improved drug bioavailability, tumor targeting, and immune stimulation, showcasing their potential in personalized medicine. This review highlights their multifaceted role in the tumor microenvironment, and their mechanisms of action in solid cancer therapy. Additionally, we discuss emerging strategies to overcome clinical and technical hurdles, paving the way for novel and effective cancer treatments.
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Affiliation(s)
- Tomas Zemanek
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Bratislava, Slovakia
- GAMMA - ZA s.r.o., Trencin, Slovakia
| | - Lubos Danisovic
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Bratislava, Slovakia
| | - Andreas Nicodemou
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
- GAMMA - ZA s.r.o., Trencin, Slovakia.
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15
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Aghajani S, Maboudi SA, Seyhoun I, Nia RR, Shabestari AN, Sharif S, Daneshi M, Verdi J. Review of mesenchymal stem cell-derived exosomes and their potential therapeutic roles in treating rheumatoid arthritis. Mol Biol Rep 2025; 52:229. [PMID: 39948229 DOI: 10.1007/s11033-025-10290-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 01/22/2025] [Indexed: 05/09/2025]
Abstract
Mesenchymal stem cells (MSCs), one of the most significant categories of stem cells, have garnered considerable attention for their potential in disease treatment due to their unique regenerative properties. MSCs can modulate immune responses through various mechanisms, including the secretion of anti-inflammatory cytokines like IL-10, TGF-β, and extracellular vesicles such as exosomes. The immunomodulatory properties of exosomes have led to their use in treating multiple autoimmune diseases, including rheumatoid arthritis (RA), a common inflammatory joint disease worldwide. Patients with RA experience chronic joint pain, movement disorders, joint and cartilage deformities, and significant treatment costs. The primary treatments for RA consist of pharmacological, non-pharmacological, and surgical methods, which mainly focus on alleviating symptoms and relieving pain rather than offering a complete cure for the disease. Recent clinical trials suggest that cell therapy along with exosome therapy, may be a promising and effective treatment option. Exosomes possess unique features that enable them to transport a variety of medicinal and biological compounds, as well as secrete anti-inflammatory substances and growth factors. Thus, exosomes can help reduce inflammation and pain in patients with rheumatoid arthritis while promoting joint repair and regeneration. In this review, we discuss the remarkable therapeutic effects of MSC-derived exosomes in reducing inflammation, facilitating joint repair, and providing pain relief in RA patients. We also detail the characteristics of MSC-derived exosomes, their isolation techniques, and the pathways of their secretion.
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Affiliation(s)
- S Aghajani
- Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - S A Maboudi
- Department of Nano Technology, Tarbiat Modares University, Tehran, Iran
| | - I Seyhoun
- Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - R Rahim Nia
- Department of NanoMedicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - A Namazi Shabestari
- Department of Geriatric Medicine, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Sh Sharif
- Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - M Daneshi
- Department of Medical Laboratory Science, Islamic Azad University Arak Branch, Arak, Iran
| | - Javad Verdi
- Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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16
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Li H, Zhang P, Lin M, Li K, Zhang C, He X, Gao K. Pyroptosis: candidate key targets for mesenchymal stem cell-derived exosomes for the treatment of bone-related diseases. Stem Cell Res Ther 2025; 16:68. [PMID: 39940049 PMCID: PMC11816542 DOI: 10.1186/s13287-025-04167-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 01/21/2025] [Indexed: 02/14/2025] Open
Abstract
Bone-related diseases impact a large portion of the global population and, due to their high disability rates and limited treatment options, pose significant medical and economic challenges. Mesenchymal stem cells (MSCs) can differentiate into multiple cell types and offer strong regenerative potential, making them promising for treating various diseases. However, issues with the immune response and cell survival limit the effectiveness of cell transplantation. This has led to increased interest in cell-free stem cell therapy, particularly the use of exosomes, which is the most studied form of this approach. Exosomes are extracellular vesicles that contain proteins, lipids, and nucleic acids and play a key role in cell communication and material exchange. Pyroptosis, a form of cell death involved in innate immunity, is also associated with many diseases. Studies have shown that MSC-derived exosomes have therapeutic potential for treating a range of conditions by regulating inflammation and pyroptosis. This study explored the role of MSC-derived exosomes in modulating pyroptosis to improve the treatment of bone-related diseases.
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Affiliation(s)
- Haiming Li
- Shandong University of Traditional Chinese Medicine, Jinan, CN, China
| | - Peng Zhang
- Department of Orthopaedics, Jining No. 1 People's Hospital, Jining, 272011, People's Republic of China
| | - Minghui Lin
- Shandong University of Traditional Chinese Medicine, Jinan, CN, China
| | - Kang Li
- Department of Spine Surgery, Jining No. 1 People's Hospital, Jining, 272011, People's Republic of China
| | - Cunxin Zhang
- Department of Spine Surgery, Jining No. 1 People's Hospital, Jining, 272011, People's Republic of China.
| | - Xiao He
- Department of Orthopaedics, Jining No. 1 People's Hospital, Jining, 272011, People's Republic of China.
| | - Kai Gao
- Shandong University of Traditional Chinese Medicine, Jinan, CN, China.
- Department of Orthopaedics, Jining No. 1 People's Hospital, Jining, 272011, People's Republic of China.
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17
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Sung SE, Seo MS, Park WT, Lim YJ, Park S, Lee GW. Extracellular vesicles: their challenges and benefits as potential biomarkers for musculoskeletal disorders. J Int Med Res 2025; 53:3000605251317476. [PMID: 39973226 PMCID: PMC11840854 DOI: 10.1177/03000605251317476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 01/10/2025] [Indexed: 02/21/2025] Open
Abstract
Early diagnosis and timely management are critical for determining disease outcomes and prognoses. To date, certain methods for developing disease-specific biomarkers have been reported; however, strategies for musculoskeletal disease-specific biomarker development have rarely been studied. Recent studies have highlighted the potential application of extracellular vesicles (EVs) as disease-specific biomarkers. EVs encapsulate proteins, lipids, messenger RNAs, and microRNAs derived from their cellular origin; these constituents remain stable within the EVs and can traverse the blood-brain barrier. Because of these distinctive characteristics, EVs have been actively investigated as diagnostic tools for various conditions, including cancer, inflammatory diseases, and musculoskeletal disorders. Although EVs have many advantages for biomarker development, they have not yet been fully researched in the context of musculoskeletal pathologies. The current review aimed to highlight the potential of EVs in the development of disease-specific biomarkers, summarize the processes of EV biomarkers, and discuss current limitations and future perspectives of EVs as biomarkers.
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Affiliation(s)
- Soo-Eun Sung
- Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI hub), Daegu, Republic of Korea
| | - Min-Soo Seo
- Department of Veterinary Tissue Engineering, College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Wook-Tae Park
- Department of Orthopedic Surgery, Yeungnam University College of Medicine, Yeungnam University Medical Center, Daegu, Republic of Korea
| | - Young-Ju Lim
- Department of Orthopedic Surgery, Yeungnam University College of Medicine, Yeungnam University Medical Center, Daegu, Republic of Korea
| | - Sangbum Park
- Department of Cell and Molecular Biology, The Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA
| | - Gun Woo Lee
- Department of Orthopedic Surgery, Yeungnam University College of Medicine, Yeungnam University Medical Center, Daegu, Republic of Korea
- Department of Cell and Molecular Biology, The Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA
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18
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Abedi A, Moosazadeh Moghaddam M, Kachuei R, Imani Fooladi AA. Exosomes as a Therapeutic Strategy in Cancer: Potential Roles as Drug Carriers and Immune Modulators. Biochim Biophys Acta Rev Cancer 2025; 1880:189238. [PMID: 39674417 DOI: 10.1016/j.bbcan.2024.189238] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 12/04/2024] [Accepted: 12/05/2024] [Indexed: 12/16/2024]
Abstract
Exosome-based cancer immunotherapy is advancing quickly on the concept of artificially activating the immune system to combat cancer. They can mechanistically change the tumor microenvironment, increase immune responses, and function as efficient drug delivery vehicles because of their inherent bioactivity, low toxicity, and immunogenicity. Accurate identification of the mechanisms of action of exosomes in tumor environments, along with optimization of their isolation, purification, and characterization methods, is necessary to increase clinical applications. Exosomes can be modified through cargo loading and surface modification to enhance their therapeutic applications, either before or after the donor cells' isolation. These engineered exosomes can directly target tumor cells at the tumor site or indirectly activate innate and adaptive immune responses in the tumor microenvironment. This approach is particularly effective when combined with traditional cancer immunotherapy techniques such as vaccines, immune checkpoints, and CAR-T cells. It can improve anti-tumor responses, induce long-term immunity, and address the limitations of traditional therapies, such as poor penetration in solid tumors and immunosuppressive environments. This review aims to provide a comprehensive and detailed overview of the direct role of engineered exosomes as drug delivery systems and their immunomodulatory effects on tumors as an indirect approach to fighting cancer. Additionally, it will discuss novel immunotherapy options.
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Affiliation(s)
- Azam Abedi
- Tissue Engineering and Regenerative Medicine Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mehrdad Moosazadeh Moghaddam
- Tissue Engineering and Regenerative Medicine Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Reza Kachuei
- Molecular Biology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Abbas Ali Imani Fooladi
- Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
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19
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José Sánchez M, Leivar P, Borrós S, Fornaguera C, Lecina M. Enhanced quantification and cell tracking of dual fluorescent labeled extracellular vesicles. Int J Pharm 2024; 667:124921. [PMID: 39521157 DOI: 10.1016/j.ijpharm.2024.124921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 11/05/2024] [Accepted: 11/06/2024] [Indexed: 11/16/2024]
Abstract
Extracellular Vesicles (EVs) are nanosized particles with significant role in disease pathogenesis and as therapeutic potential. However, the lack of reliable and efficient methods for the characterization, quantification and tracking of EVs, combined with the limitations of detection techniques in differentiating specific EVs subtypes with beneficial properties, makes these process complex and time-consuming. To address this challenge, EVs were engineered using a tricistronic plasmid that encodes fluorescent proteins fused to tetraspanins (eGFP-CD63 and mCherry-CD9), with both fluorophores localized within the luminal space. Double fluorescently labelled small EVs (sEVs) were then produced in a stably transfected HEK293SF-3F6 cell line. The fluorescently labelled sEVs were characterized using a variety of techniques. Protein expression analysis showed that the fused proteins were efficiently produced and incorporated in sEVs, as evidenced by clear fluorescence signal detected. Comparisons of the size distribution and concentration of modified sEVs with controls indicated that sEVs engineering did not affect their biogenesis and morphology. Fluorescently labelled sEVs were then quantified by flow cytometry, allowing to distinguish sEVs from other EVs subtypes or sample particles. The values were then compared to fluorometry measurements, obtaining a linear correlation what enabled a novel sEVs quantification method. The functionality of engineered sEVs was assessed by monitoring their uptake and trafficking in recipient cells, obtaining an efficient internalisation by target cells. Overall, these results demonstrate that the implementation of dual fluorescent methodology is feasible for sEVs characterization, quantification, for in vitro study of EVs interaction with cells, and intercellular communication, as well as a valuable tool in the in vitro development of targeted therapeutic EVs delivery systems.
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Affiliation(s)
- Maria José Sánchez
- Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià (IQS), Univeritat Ramon Llull (URL), Barcelona 08017, Spain
| | - Pablo Leivar
- Laboratory of Biochemistry, Institut Químic de Sarrià (IQS), Universitat Ramon Llull (URL), Barcelona 08017, Spain
| | - Salvador Borrós
- Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià (IQS), Univeritat Ramon Llull (URL), Barcelona 08017, Spain
| | - Cristina Fornaguera
- Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià (IQS), Univeritat Ramon Llull (URL), Barcelona 08017, Spain
| | - Martí Lecina
- Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià (IQS), Univeritat Ramon Llull (URL), Barcelona 08017, Spain.
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20
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Yadav S, Maity P, Kapat K. The Opportunities and Challenges of Mesenchymal Stem Cells-Derived Exosomes in Theranostics and Regenerative Medicine. Cells 2024; 13:1956. [PMID: 39682706 PMCID: PMC11640604 DOI: 10.3390/cells13231956] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 11/19/2024] [Accepted: 11/22/2024] [Indexed: 12/18/2024] Open
Abstract
Cell-secreted nanovesicles of endosomal origin, called exosomes, are vital for mediating intracellular communication. As local or distal transporters of intracellular cargo, they reflect the unique characteristics of secretory cells and establish cell-specific interactions via characteristic surface proteins and receptors. With the advent of rapid isolation, purification, and identification techniques, exosomes have become an attractive choice for disease diagnosis (exosomal content as biomarkers), cell-free therapy, and tissue regeneration. Mesenchymal stem cell (MSC)-derived exosomes (MSC-exosomes) display angiogenic, immune-modulatory, and other therapeutic effects crucial for cytoprotection, ischemic wound repair, myocardial regeneration, etc. The primary focus of this review is to highlight the widespread application of MSC-exosomes in therapeutics, theranostics, and tissue regeneration. After a brief introduction of exosome properties, biogenesis, isolation, and functions, recent studies on therapeutic and regenerative applications of MSC-exosomes are described, focusing on bone, cartilage, periodontal, cardiovascular, skin, and nerve regeneration. Finally, the review highlights the theranostic potential of exosomes followed by challenges, summary, and outlook.
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Affiliation(s)
- Sachin Yadav
- Department of Medical Devices, National Institute of Pharmaceutical Education and Research Kolkata, 168, Maniktala Main Road, Kankurgachi, Kolkata 700054, West Bengal, India;
| | - Pritiprasanna Maity
- School of Medicine, University of California Riverside, Riverside, CA 92525, USA
| | - Kausik Kapat
- Department of Medical Devices, National Institute of Pharmaceutical Education and Research Kolkata, 168, Maniktala Main Road, Kankurgachi, Kolkata 700054, West Bengal, India;
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21
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Mastantuono S, Manini I, Di Loreto C, Beltrami AP, Vindigni M, Cesselli D. Glioma-Derived Exosomes and Their Application as Drug Nanoparticles. Int J Mol Sci 2024; 25:12524. [PMID: 39684236 DOI: 10.3390/ijms252312524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 11/19/2024] [Indexed: 12/18/2024] Open
Abstract
Glioblastoma Multiforme (GBM) is the most aggressive primary tumor of the Central Nervous System (CNS) with a low survival rate. The malignancy of GBM is sustained by a bidirectional crosstalk between tumor cells and the Tumor Microenvironment (TME). This mechanism of intercellular communication is mediated, at least in part, by the release of exosomes. Glioma-Derived Exosomes (GDEs) work, indeed, as potent signaling particles promoting the progression of brain tumors by inducing tumor proliferation, invasion, migration, angiogenesis and resistance to chemotherapy or radiation. Given their nanoscale size, exosomes can cross the blood-brain barrier (BBB), thus becoming not only a promising biomarker to predict diagnosis and prognosis but also a therapeutic target to treat GBM. In this review, we describe the structural and functional characteristics of exosomes and their involvement in GBM development, diagnosis, prognosis and treatment. In addition, we discuss how exosomes can be modified to be used as a therapeutic target/drug delivery system for clinical applications.
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Affiliation(s)
- Serena Mastantuono
- Department of Medicine, University of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, Italy
| | - Ivana Manini
- Department of Pathological Anatomy, University Hospital of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, Italy
| | - Carla Di Loreto
- Department of Pathological Anatomy, University Hospital of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, Italy
| | - Antonio Paolo Beltrami
- Department of Medicine, University of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, Italy
- Institute of Clinical Pathology, University Hospital of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, Italy
| | - Marco Vindigni
- Department of Neurosurgery, University Hospital of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, Italy
| | - Daniela Cesselli
- Department of Medicine, University of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, Italy
- Department of Pathological Anatomy, University Hospital of Udine, Piazzale S. Maria della Misericordia 15, 33100 Udine, Italy
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22
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Zhang R, Li D, Zhou Z, Hong H, Shi J, Wu Z. Chemo-Enzymatic Functionalization of Bovine Milk Exosomes with an EGFR Nanobody for Target-specific Drug Delivery. Chembiochem 2024; 25:e202400512. [PMID: 39192477 DOI: 10.1002/cbic.202400512] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 08/16/2024] [Accepted: 08/27/2024] [Indexed: 08/29/2024]
Abstract
Bovine milk exosomes (BmExo) have been identified as versatile nanovesicles for anti-cancer drugs delivery due to their natural availability and biocompatibility. However, tumor-specific delivery based on BmExo often requires post-isolation modifications of the membrane surface with active-targeting ligands. In this study, we report an alternative approach to functionalize BmExo with nanobody combining facile chemical modification and Sortase A-mediated site-specific ligation, as demonstrated by the development of an epidermal growth factor receptor (EGFR)-targeted drug delivery system. The BmExo membrane was first coated with a diglycine-containing amphiphile molecule, NH2-GG-PEG2000-DSPE, by hydrophobic insertion. The diglycine as nucleophiles displayed on the membrane enabled the subsequent ligation of the EGFR nanobody (7D12) by Sortase A (SrtA)-mediated site-specific transpeptidation. The successful construction of BmExo-7D12 was confirmed by Western blotting analysis, electron microscopy, and dynamic light scattering (DLS). As a demonstration model, BmExo-7D12 loaded with the chemotherapeutic drug doxorubicin (Dox) was shown to be able to deliver Dox to cancer cells in response to the expression of EGFR as manifested by immunocytochemistry and flow cytometry analysis. Finally, the cytotoxicity assay showed that BmExo-7D12-Dox was more effective in killing tumor cells with high EGFR expression while significantly reduced the non-specific toxicity to EGFR negative cells. In conclusion, these results demonstrate that 7D12-functionalized BmExo can serve as a target-specific delivery system for Dox to selectively kill EGFR-expressing tumor cells. This approach should prove to be versatile and efficient for the generation of protein-ligands modified BmExo.
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Affiliation(s)
- Ranran Zhang
- Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, No. 1800, Lihu Avenue, Wuxi, 214122, China
| | - Dan Li
- Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, No. 1800, Lihu Avenue, Wuxi, 214122, China
| | - Zhifang Zhou
- Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, No. 1800, Lihu Avenue, Wuxi, 214122, China
| | - Haofei Hong
- Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, No. 1800, Lihu Avenue, Wuxi, 214122, China
| | - Jie Shi
- Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, No. 1800, Lihu Avenue, Wuxi, 214122, China
| | - Zhimeng Wu
- Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, No. 1800, Lihu Avenue, Wuxi, 214122, China
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Chatterji T, Khanna N, Alghamdi S, Bhagat T, Gupta N, Alkurbi MO, Sen M, Alghamdi SM, Bamagous GA, Sahoo DK, Patel A, Kumar P, Yadav VK. A Recent Advance in the Diagnosis, Treatment, and Vaccine Development for Human Schistosomiasis. Trop Med Infect Dis 2024; 9:243. [PMID: 39453270 PMCID: PMC11511416 DOI: 10.3390/tropicalmed9100243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 10/13/2024] [Accepted: 10/14/2024] [Indexed: 10/26/2024] Open
Abstract
Schistosomiasis, which affects a large number of people worldwide, is among the most overlooked parasitic diseases. The disease is mainly prevalent in sub-Saharan Africa, southeast Asian countries, and South America due to the lack of adequate sanitation. The disease is mainly associated with poor hygiene, sanitation, and contaminated water, so it is also known as a disease of poverty. Three Schistosoma species (S. mansoni, S. japonicum, and S. haematobium) cause significant human infections. Co-infections with Schistosoma and other parasites are widely common. All these parasites may cause intestinal or urogenital schistosomiasis, where the disease may be categorized into the acute, sensitized, and chronic phases. The disease is more prevalent among school children, which may cause anemia and reduce development. Chronic infections frequently cause significant liver, intestinal, and bladder damage. Women exposed to contaminated water while performing normal duties like washing clothes might acquire urogenital schistosomiasis (UGS), which can cause tissue damage and raise the risk of blood-borne disease transmission, including human immunodeficiency virus (HIV) transmission. Praziquantel (PZQ) is the World Health Organization (WHO)-prescribed treatment for individuals who are known to be infected, but it does not prevent further re-infections with larval worms. Vaccine development and new molecular-based diagnosis techniques have promised to be a reliable approach to the diagnosis and prevention of schistosomiasis. The current review emphasizes the recent advancement in the diagnosis of schistosomiasis by molecular techniques and the treatment of schistosomiasis by combined and alternative regimes of drugs. Moreover, this review has also focused on the recent outbreak of schistosomiasis, the development of vaccines, and their clinical trials.
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Affiliation(s)
- Tanushri Chatterji
- Department of Biosciences, Institute of Management Studies Ghaziabad (University Courses Campus), Adhyatmik Nagar, NH-09, Ghaziabad 201015, Uttar Pradesh, India;
| | - Namrata Khanna
- Department of Biochemistry, M A Rangoonwala College of Dental Sciences and Research Centre, 2390-B, K.B. Hidayatullah Road, Azam Campus, Camp, Pune 411001, Maharashtra, India;
| | - Saad Alghamdi
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah 21955, Saudi Arabia; (S.A.); (M.O.A.)
| | - Tanya Bhagat
- Department of Biosciences, Institute of Management Studies Ghaziabad (University Courses Campus), Adhyatmik Nagar, NH-09, Ghaziabad 201015, Uttar Pradesh, India;
| | - Nishant Gupta
- Engineering Department, River Engineering Pvt Ltd., Toy City, Ecotech–III, Greater Noida 201306, Uttar Pradesh, India;
| | - Mohammad Othman Alkurbi
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah 21955, Saudi Arabia; (S.A.); (M.O.A.)
| | - Manodeep Sen
- Department of Microbiology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Vibhuti Khand, Gomti Nagar, Lucknow 226010, Uttar Pradesh, India;
| | - Saeed Mardy Alghamdi
- Respiratory Care Program, Clinical Technology Department, Faculty of Applied Medical Science, Umm Al-Qura University, Makkah 21955, Saudi Arabia;
| | - Ghazi A. Bamagous
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia;
| | - Dipak Kumar Sahoo
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA;
| | - Ashish Patel
- Department of Life Sciences, Hemchandracharya North Gujarat University, Patan 384265, Gujarat, India;
| | - Pankaj Kumar
- Department of Environmental Science, Parul Institute of Applied Sciences, Parul University, Vadodara 391760, Gujarat, India;
| | - Virendra Kumar Yadav
- Marwadi University Research Center, Department of Microbiology, Faculty of Sciences, Marwadi University, Rajkot 360003, Gujarat, India
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Ahmed W, Mushtaq A, Ali S, Khan N, Liang Y, Duan L. Engineering Approaches for Exosome Cargo Loading and Targeted Delivery: Biological versus Chemical Perspectives. ACS Biomater Sci Eng 2024; 10:5960-5976. [PMID: 38940421 DOI: 10.1021/acsbiomaterials.4c00856] [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] [Indexed: 06/29/2024]
Abstract
Exosomes are nanoscale membrane bound vesicles secreted by almost all types of cells. Their unique attributes, such as minimal immunogenicity and compatibility with biological systems, make them novel carriers for drug delivery. These native exosomes harbor proteins, nucleic acids, small molecule compounds, and fluorogenic agents. Moreover, through a combination of chemical and bioengineering methodologies, exosomes are tailored to transport precise therapeutic payloads to designated cells or tissues. In this review, we summarize the strategies for exosome modification and drug loading modalities in engineered exosomes. In addition, we provide an overview of the advances in the use of engineered exosomes for targeted drug delivery. Lastly, we discuss the merits and limitations of chemically engineered versus bioengineered exosome-mediated target therapies. These insights offer additional options for refining engineered exosomes in pharmaceutical development and hold promise for expediting the successful translation of engineered exosomes from the bench to the bedside.
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Affiliation(s)
- Waqas Ahmed
- Department of Orthopedics, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, Guangdong, China
- Medical School, Shenzhen University, Shenzhen 518060, Guangdong, China
| | - Asim Mushtaq
- Centre for Future Materials, University of Southern Queensland, Springfield, Queensland 4300, Australia
| | - Shahzad Ali
- Department of Orthopedics, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, Guangdong, China
- Medical School, Shenzhen University, Shenzhen 518060, Guangdong, China
| | - Nawaz Khan
- Department of Orthopedics, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, Guangdong, China
- Medical School, Shenzhen University, Shenzhen 518060, Guangdong, China
| | - Yujie Liang
- Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, Shenzhen Institute of Mental Health, Shenzhen Mental Health Center, Shenzhen Clinical Research Center for Mental Disorders, Shenzhen 518020, Guangdong, China
| | - Li Duan
- Department of Orthopedics, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, Guangdong, China
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25
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Huang Y, Wang S, Hu D, Zhang L, Shi S. ALKBH5 regulates etoposide-induced cellular senescence and osteogenic differentiation in osteoporosis through mediating the m 6A modification of VDAC3. Sci Rep 2024; 14:23461. [PMID: 39379688 PMCID: PMC11461877 DOI: 10.1038/s41598-024-75033-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 10/01/2024] [Indexed: 10/10/2024] Open
Abstract
Osteoporosis, a common bone disease in older individuals, involves the progression influenced by N6-methyladenosine (m6A) modification. This study aimed to elucidate the effects of VDAC3 m6A modification on human bone mesenchymal stromal cell (BMSC) senescence and osteogenic differentiation. BMSCs were treated with etoposide to induce senescence. Senescence was assessed by β-galactosidase staining and quantitative real-time PCR (qPCR), and osteogenic differentiation was evaluated using Western blot, alkaline phosphatase, and alizarin red S staining. VDAC3 and ALKBH5 expression were quantified by qPCR, and their interaction was assessed by RNA immunoprecipitation (RIP) and luciferase reporter assay. m6A methylation was analyzed using the Me-RIP assay. VDAC3 expression was significantly decreased in etoposide-treated BMSCs (1.00 ± 0.13 vs. 0.26 ± 0.06). VDAC3 overexpression reduced etoposide-induced senescence and promoted osteogenic differentiation. ALKBH5 overexpression inhibited VDAC3 m6A modification (1.00 ± 0.095 vs. 0.233 ± 0.177) and its stability. ALKBH5 knockdown decreased etoposide-induced senescence and promoted osteogenic differentiation, effects that were reversed by VDAC3 knockdown. YTHDF1 was identified as the m6A methylation reader, and its overexpression inhibited VDAC3 stability. We demonstrated that ALKBH5 inhibited osteogenic differentiation of etoposide-induced senescent cells through the inhibition of VDAC3 m6A modification, and YTHDF1 acted as the m6A methylation reader. These findings provide a novel theoretical basis for the treatment of osteoporosis.
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Affiliation(s)
- Yansheng Huang
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710000, Shaanxi, China
| | - Sibo Wang
- Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710000, Shaanxi, China
| | - Dong Hu
- Department of Hand Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710000, Shaanxi, China
| | - Li Zhang
- Department of Hand Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710000, Shaanxi, China
| | - Shaoyan Shi
- Department of Hand Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710000, Shaanxi, China.
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26
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Akbari-Gharalari N, Ghahremani-Nasab M, Naderi R, Chodari L, Nezhadshahmohammad F. The potential of exosomal biomarkers: Revolutionizing Parkinson's disease: How do they influence pathogenesis, diagnosis, and therapeutic strategies? AIMS Neurosci 2024; 11:374-397. [PMID: 39431275 PMCID: PMC11486621 DOI: 10.3934/neuroscience.2024023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 09/10/2024] [Accepted: 09/18/2024] [Indexed: 10/22/2024] Open
Abstract
Parkinson's disease (PD) is characterized by the pathological accumulation of α-synuclein, which has driven extensive research into the role of exosomes in disease mechanisms. Exosomes are nanoscale vesicles enriched with proteins, RNA, and lipids that facilitate critical intercellular communication processes. Recent studies have elucidated the role of exosomes in transmitting misfolded proteins among neurons, which significantly impacts the progression of PD. The presence of disease-associated exosomes in cerebrospinal fluid and blood highlights their substantial diagnostic potential for PD. Specifically, exosomes derived from the central nervous system (CNS) have emerged as promising biomarkers because of their ability to accurately reflect pathological states. Furthermore, the isolation of exosomes from distinct brain cell types allows the identification of precise biomarkers, increasing diagnostic specificity and accuracy. In addition to being useful for diagnostics, exosomes hold therapeutic promise given their ability to cross the blood-brain barrier (BBB) and selectively modulate their cargo. These findings suggest that these materials could be used as delivery systems for therapeutic drugs for the treatment of neurodegenerative diseases. This review comprehensively examines the multifaceted roles of exosomes in PD pathogenesis, diagnosis, and treatment. It also addresses the associated clinical challenges and underscores the urgent need for further research and development to fully leverage exosome-based strategies in PD management.
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Affiliation(s)
- Naeimeh Akbari-Gharalari
- Department of Physiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
- Neurophysiology Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Maryam Ghahremani-Nasab
- Department of Tissue Engineering, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Roya Naderi
- Department of Physiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
- Neurophysiology Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Leila Chodari
- Department of Physiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
- Neurophysiology Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
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27
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Al-Ani SA, Lee QY, Maheswaran D, Sin YM, Loh JS, Foo JB, Hamzah S, Ng JF, Tan LKS. Potential of Exosomes as Multifunctional Nanocarriers for Targeted Drug Delivery. Mol Biotechnol 2024:10.1007/s12033-024-01268-6. [PMID: 39269575 DOI: 10.1007/s12033-024-01268-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 08/24/2024] [Indexed: 09/15/2024]
Abstract
Exosomes are small vesicles that form when multivesicular bodies fuse with the plasma membrane and are released into body fluids. They play a vital role in facilitating communication between cells by transferring different biomolecules, including DNA, RNA, proteins, and lipids, over both short and long distances. They also function as vital mediators in both states of health and disease, exerting an impact on several physiological processes. Exosomes have been modified to overcome the limitations of natural exosomes to enhance their potential as carriers for drug delivery systems, and these modifications aim to improve the drug delivery efficiency, enhance tissue and organ targeting, and prolong the circulating half-life of exosomes. This review discussed recent advancements in exosome nanotechnology, as well as the progression and use of exosomes for drug delivery. The potential commercialisation and challenges associated with the use of exosome-based drug delivery systems were also discussed, aiming to motivate the development of exosome-based theranostic nanoplatforms and nanotechnology for improved healthcare treatments.
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Affiliation(s)
- Safa Ali Al-Ani
- School of Pharmacy, Faculty of Health & Medical Sciences, Taylor's University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia
| | - Qiao Ying Lee
- School of Pharmacy, Faculty of Health & Medical Sciences, Taylor's University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia
| | - Danesha Maheswaran
- School of Pharmacy, Faculty of Health & Medical Sciences, Taylor's University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia
| | - Yuh Miin Sin
- Faculty of Medicine, AIMST University, Jalan Bedong, 08100, Semeling, Kedah Darulaman, Malaysia
| | - Jian Sheng Loh
- School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor, Malaysia
| | - Jhi Biau Foo
- School of Pharmacy, Faculty of Health & Medical Sciences, Taylor's University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia
- Digital Health and Medical Advancements Impact Lab, Taylor's University, 47500, Subang Jaya, Selangor, Malaysia
- Non-Destructive Biomedical and Pharmaceutical Research Centre, Smart Manufacturing Research Institute, Universiti Teknologi MARA Selangor campus, 42300 Puncak Alam, Selangor, Malaysia
| | - Sharina Hamzah
- School of Pharmacy, Faculty of Health & Medical Sciences, Taylor's University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia
- Digital Health and Medical Advancements Impact Lab, Taylor's University, 47500, Subang Jaya, Selangor, Malaysia
| | - Jeck Fei Ng
- School of Pharmacy, Faculty of Health & Medical Sciences, Taylor's University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia
- Digital Health and Medical Advancements Impact Lab, Taylor's University, 47500, Subang Jaya, Selangor, Malaysia
| | - Li Kar Stella Tan
- School of Pharmacy, Faculty of Health & Medical Sciences, Taylor's University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia.
- Digital Health and Medical Advancements Impact Lab, Taylor's University, 47500, Subang Jaya, Selangor, Malaysia.
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28
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Wang M, Hong Y, Fu X, Sun X. Advances and applications of biomimetic biomaterials for endogenous skin regeneration. Bioact Mater 2024; 39:492-520. [PMID: 38883311 PMCID: PMC11179177 DOI: 10.1016/j.bioactmat.2024.04.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 04/11/2024] [Accepted: 04/11/2024] [Indexed: 06/18/2024] Open
Abstract
Endogenous regeneration is becoming an increasingly important strategy for wound healing as it facilitates skin's own regenerative potential for self-healing, thereby avoiding the risks of immune rejection and exogenous infection. However, currently applied biomaterials for inducing endogenous skin regeneration are simplistic in their structure and function, lacking the ability to accurately mimic the intricate tissue structure and regulate the disordered microenvironment. Novel biomimetic biomaterials with precise structure, chemical composition, and biophysical properties offer a promising avenue for achieving perfect endogenous skin regeneration. Here, we outline the recent advances in biomimetic materials induced endogenous skin regeneration from the aspects of structural and functional mimicry, physiological process regulation, and biophysical property design. Furthermore, novel techniques including in situ reprograming, flexible electronic skin, artificial intelligence, single-cell sequencing, and spatial transcriptomics, which have potential to contribute to the development of biomimetic biomaterials are highlighted. Finally, the prospects and challenges of further research and application of biomimetic biomaterials are discussed. This review provides reference to address the clinical problems of rapid and high-quality skin regeneration.
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Affiliation(s)
- Mengyang Wang
- Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department, PLA General Hospital and PLA Medical College, Beijing, 100853, PR China
- PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, Beijing, 100089, PR China
| | - Yiyue Hong
- Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department, PLA General Hospital and PLA Medical College, Beijing, 100853, PR China
- PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, Beijing, 100089, PR China
| | - Xiaobing Fu
- Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department, PLA General Hospital and PLA Medical College, Beijing, 100853, PR China
- PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, Beijing, 100089, PR China
- Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, PR China
| | - Xiaoyan Sun
- Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Department, PLA General Hospital and PLA Medical College, Beijing, 100853, PR China
- PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, Beijing, 100089, PR China
- Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, 2019RU051, Beijing, 100048, PR China
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29
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Song W, Guo Y, Liu W, Yao Y, Zhang X, Cai Z, Yuan C, Wang X, Wang Y, Jiang X, Wang H, Yu W, Li H, Zhu Y, Kong L, He Y. Circadian Rhythm-Regulated ADSC-Derived sEVs and a Triphasic Microneedle Delivery System to Enhance Tendon-to-Bone Healing. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2408255. [PMID: 39120049 DOI: 10.1002/adma.202408255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 07/23/2024] [Indexed: 08/10/2024]
Abstract
Modulating the inflammatory microenvironment to reconstruct the fibrocartilaginous layer while promoting tendon repair is crucial for enhancing tendon-to-bone healing in rotator cuff repair (RCR), a persistent challenge in orthopedics. Small extracellular vesicles (sEVs) hold significant potential to modulate inflammation, yet the efficient production of highly bioactive sEVs remains a substantial barrier to their clinical application. Moreover, achieving minimally invasive local delivery of sEVs to the tendon-to-bone interface presents significant technical difficulties. Herein, the circadian rhythm of adipose-derived stem cells is modulated to increase the yield and enhance the inflammatory regulatory capacity of sEVs. Circadian rhythm-regulated sEVs (CR-sEVs) enhance the cyclic adenosine monophosphate signaling pathway in macrophage (Mφ) via platelet factor 4 delivery, thereby inhibiting Mφ M1 polarization. Subsequently, a triphasic microneedle (MN) scaffold with a tip, stem, and base is designed for the local delivery of CR-sEVs (CR-sEVs/MN) at the tendon-to-bone junction, incorporating tendon-derived decellularized extracellular matrix in the base to facilitate tendon repair. CR-sEVs/MN mitigates inflammation, promotes fibrocartilage regeneration, and enhances tendon healing, thereby improving biomechanical strength and shoulder joint function in a rat RCR model. Combining CR-sEVs with this triphasic microneedle delivery system presents a promising strategy for enhancing tendon-to-bone healing in clinical settings.
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Affiliation(s)
- Wei Song
- Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, P. R. China
| | - Ying Guo
- Department of Cardiology, Heart Center, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P. R. China
| | - Wencai Liu
- Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, P. R. China
| | - Yijing Yao
- Department of Ultrasound, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, P. R. China
| | - Xuancheng Zhang
- Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, P. R. China
| | - Zhuochang Cai
- Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, P. R. China
| | - Chenrui Yuan
- Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, P. R. China
| | - Xin Wang
- Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, P. R. China
| | - Yifei Wang
- Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, P. R. China
| | - Xiping Jiang
- Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, P. R. China
| | - Haoyuan Wang
- Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, P. R. China
| | - Weilin Yu
- Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, P. R. China
| | - Haiyan Li
- Chemical and Environmental Engineering Department, School of Engineering, STEM College, RMIT University, 124 La Trobe St., Melbourne, Victoria, 3000, Australia
| | - Yanlun Zhu
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, P. R. China
| | - Lingzhi Kong
- Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, P. R. China
| | - Yaohua He
- Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, P. R. China
- Department of Orthopedic Surgery, Jinshan District Central Hospital affiliated to Shanghai University of Medicine & Health Sciences, Jinshan Branch of Shanghai Sixth People's Hospital, Shanghai, 201500, P. R. China
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30
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Jin H, Liu J, Wang D. Antioxidant Potential of Exosomes in Animal Nutrition. Antioxidants (Basel) 2024; 13:964. [PMID: 39199210 PMCID: PMC11351667 DOI: 10.3390/antiox13080964] [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: 06/28/2024] [Revised: 08/05/2024] [Accepted: 08/06/2024] [Indexed: 09/01/2024] Open
Abstract
This review delves into the advantages of exosomes as novel antioxidants in animal nutrition and their potential for regulating oxidative stress. Although traditional nutritional approaches promote oxidative stress defense systems in mammalian animals, several issues remain to be solved, such as low bioavailability, targeted tissue efficiency, and high-dose by-effect. As an important candidate offering regulation opportunities concerned with cellular communication, disease prevention, and physiology regulation in multiple biological systems, the potential of exosomes in mediating redox status in biological systems has not been well described. A previously reported relationship between redox system regulation and circulating exosomes suggested exosomes as a fundamental candidate for both a regulator and biomarker for a redox system. Herein, we review the effects of oxidative stress on exosomes in animals and the potential application of exosomes as antioxidants in animal nutrition. Then, we highlight the advantages of exosomes as redox regulators due to their higher bioavailability and physiological heterogeneity-targeted properties, providing a theoretical foundation and feed industry application. Therefore, exosomes have shown great potential as novel antioxidants in the field of animal nutrition. They can overcome the limitations of traditional antioxidants in terms of dosage and side effects, which will provide unprecedented opportunities in nutritional management and disease prevention, and may become a major breakthrough in the field of animal nutrition.
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Affiliation(s)
| | | | - Diming Wang
- Institute of Dairy Science, MoE Key Laboratory of Molecular Animal Nutrition, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China; (H.J.); (J.L.)
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Guo L, Xiao D, Xing H, Yang G, Yang X. Engineered exosomes as a prospective therapy for diabetic foot ulcers. BURNS & TRAUMA 2024; 12:tkae023. [PMID: 39026930 PMCID: PMC11255484 DOI: 10.1093/burnst/tkae023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 03/29/2024] [Indexed: 07/20/2024]
Abstract
Diabetic foot ulcer (DFU), characterized by high recurrence rate, amputations and mortality, poses a significant challenge in diabetes management. The complex pathology involves dysregulated glucose homeostasis leading to systemic and local microenvironmental complications, including peripheral neuropathy, micro- and macro-angiopathy, recurrent infection, persistent inflammation and dysregulated re-epithelialization. Novel approaches to accelerate DFU healing are actively pursued, with a focus on utilizing exosomes. Exosomes are natural nanovesicles mediating cellular communication and containing diverse functional molecular cargos, including DNA, mRNA, microRNA (miRNA), lncRNA, proteins, lipids and metabolites. While some exosomes show promise in modulating cellular function and promoting ulcer healing, their efficacy is limited by low yield, impurities, low loading content and inadequate targeting. Engineering exosomes to enhance their curative activity represents a potentially more efficient approach for DFUs. This could facilitate focused repair and regeneration of nerves, blood vessels and soft tissue after ulcer development. This review provides an overview of DFU pathogenesis, strategies for exosome engineering and the targeted therapeutic application of engineered exosomes in addressing critical pathological changes associated with DFUs.
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Affiliation(s)
- Lifei Guo
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Chang-Le Xi Street #127, Xi'an 710032, China
- The State Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Chang-Le Xi Street #127, Xi'an 710032, China
- Cadet Team 6 of School of Basic Medicine, Fourth Military Medical University, Chang-Le Xi Street #127, Xi'an 710032, China
| | - Dan Xiao
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Chang-Le Xi Street #127, Xi'an 710032, China
- The State Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Chang-Le Xi Street #127, Xi'an 710032, China
| | - Helin Xing
- Department of Prosthodontics, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, Tiantanxili Street #4, Dongcheng District, Beijing 100050, China
| | - Guodong Yang
- The State Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Chang-Le Xi Street #127, Xi'an 710032, China
| | - Xuekang Yang
- Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Chang-Le Xi Street #127, Xi'an 710032, China
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Taeb S, Rostamzadeh D, Amini SM, Rahmati M, Eftekhari M, Safari A, Najafi M. MicroRNAs targeted mTOR as therapeutic agents to improve radiotherapy outcome. Cancer Cell Int 2024; 24:233. [PMID: 38965615 PMCID: PMC11229485 DOI: 10.1186/s12935-024-03420-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 06/22/2024] [Indexed: 07/06/2024] Open
Abstract
MicroRNAs (miRNAs) are small RNA molecules that regulate genes and are involved in various biological processes, including cancer development. Researchers have been exploring the potential of miRNAs as therapeutic agents in cancer treatment. Specifically, targeting the mammalian target of the rapamycin (mTOR) pathway with miRNAs has shown promise in improving the effectiveness of radiotherapy (RT), a common cancer treatment. This review provides an overview of the current understanding of miRNAs targeting mTOR as therapeutic agents to enhance RT outcomes in cancer patients. It emphasizes the importance of understanding the specific miRNAs that target mTOR and their impact on radiosensitivity for personalized cancer treatment approaches. The review also discusses the role of mTOR in cell homeostasis, cell proliferation, and immune response, as well as its association with oncogenesis. It highlights the different ways in which miRNAs can potentially affect the mTOR pathway and their implications in immune-related diseases. Preclinical findings suggest that combining mTOR modulators with RT can inhibit tumor growth through anti-angiogenic and anti-vascular effects, but further research and clinical trials are needed to validate the efficacy and safety of using miRNAs targeting mTOR as therapeutic agents in combination with RT. Overall, this review provides a comprehensive understanding of the potential of miRNAs targeting mTOR to enhance RT efficacy in cancer treatment and emphasizes the need for further research to translate these findings into improved clinical outcomes.
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Affiliation(s)
- Shahram Taeb
- Department of Radiology, School of Paramedical Sciences, Guilan University of Medical Sciences, Rasht, Iran
| | - Davoud Rostamzadeh
- Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA
| | - Seyed Mohammad Amini
- Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Rahmati
- Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Mohammad Eftekhari
- Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Arash Safari
- Department of Radiology, Ionizing and Non-Ionizing Radiation Protection Research Center (INIRPRC), School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, 71439-14693, Iran
| | - Masoud Najafi
- Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Medical Biology Research Center, Institute of Health Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Medical Technology Research Center, Institute of Health Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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33
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Choudhery MS, Arif T, Mahmood R, Harris DT. Stem Cell-Based Acellular Therapy: Insight into Biogenesis, Bioengineering and Therapeutic Applications of Exosomes. Biomolecules 2024; 14:792. [PMID: 39062506 PMCID: PMC11275160 DOI: 10.3390/biom14070792] [Citation(s) in RCA: 13] [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: 06/06/2024] [Revised: 06/25/2024] [Accepted: 06/28/2024] [Indexed: 07/28/2024] Open
Abstract
The vast regenerative potential of stem cells has laid the foundation for stem cell-based therapies. However, certain challenges limit the application of cell-based therapies. The therapeutic use of cell-free therapy can avoid limitations associated with cell-based therapies. Acellular stem cell-based therapies rely on the use of biological factors released by stem cells, including growth factors and extracellular vesicles such as exosomes. Due to their comparable regenerative potential, acellular therapies may provide a feasible and scalable alternative to stem cell-based therapies. Exosomes are small vesicles secreted by various types of cells, including stem cells. Exosomes contain parent cell-derived nucleic acids, proteins, lipids, and other bioactive molecules. They play an important role in intra-cellular communication and influence the biological characteristics of cells. Exosomes inherit the properties of their parent cells; therefore, stem cell-derived exosomes are of particular interest for applications of regenerative medicine. In comparison to stem cell-based therapy, exosome therapy offers several benefits, such as easy transport and storage, no risk of immunological rejection, and few ethical dilemmas. Unlike stem cells, exosomes can be lyophilized and stored off-the-shelf, making acellular therapies standardized and more accessible while reducing overall treatment costs. Exosome-based acellular treatments are therefore readily available for applications in patients at the time of care. The current review discusses the use of exosomes as an acellular therapy. The review explores the molecular mechanism of exosome biogenesis, various methods for exosome isolation, and characterization. In addition, the latest advancements in bioengineering techniques to enhance exosome potential for acellular therapies have been discussed. The challenges in the use of exosomes as well as their diverse applications for the diagnosis and treatment of diseases have been reviewed in detail.
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Affiliation(s)
- Mahmood S. Choudhery
- Department of Human Genetics & Molecular Biology, University of Health Sciences, Lahore 54600, Pakistan; (M.S.C.); (T.A.)
| | - Taqdees Arif
- Department of Human Genetics & Molecular Biology, University of Health Sciences, Lahore 54600, Pakistan; (M.S.C.); (T.A.)
| | - Ruhma Mahmood
- Allama Iqbal Medical College, Jinnah Hospital, Lahore 54700, Pakistan;
| | - David T. Harris
- Department of Immunobiology, College of Medicine, University of Arizona Health Sciences Biorepository, University of Arizona, Tucson, AZ 85721, USA
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Haider KH. Priming mesenchymal stem cells to develop "super stem cells". World J Stem Cells 2024; 16:623-640. [PMID: 38948094 PMCID: PMC11212549 DOI: 10.4252/wjsc.v16.i6.623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 05/04/2024] [Accepted: 05/20/2024] [Indexed: 06/25/2024] Open
Abstract
The stem cell pre-treatment approaches at cellular and sub-cellular levels encompass physical manipulation of stem cells to growth factor treatment, genetic manipulation, and chemical and pharmacological treatment, each strategy having advantages and limitations. Most of these pre-treatment protocols are non-combinative. This editorial is a continuum of Li et al's published article and Wan et al's editorial focusing on the significance of pre-treatment strategies to enhance their stemness, immunoregulatory, and immunosuppressive properties. They have elaborated on the intricacies of the combinative pre-treatment protocol using pro-inflammatory cytokines and hypoxia. Applying a well-defined multi-pronged combinatorial strategy of mesenchymal stem cells (MSCs), pre-treatment based on the mechanistic understanding is expected to develop "Super MSCs", which will create a transformative shift in MSC-based therapies in clinical settings, potentially revolutionizing the field. Once optimized, the standardized protocols may be used with slight modifications to pre-treat different stem cells to develop "super stem cells" with augmented stemness, functionality, and reparability for diverse clinical applications with better outcomes.
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Affiliation(s)
- Khawaja Husnain Haider
- Department of Basic Sciences, Sulaiman AlRajhi University, AlQaseem 52736, Saudi Arabia.
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Kathait P, Patel PK, Sahu AN. Harnessing exosomes and plant-derived exosomes as nanocarriers for the efficient delivery of plant bioactives. Nanomedicine (Lond) 2024; 19:2679-2697. [PMID: 38900607 DOI: 10.1080/17435889.2024.2354159] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 05/08/2024] [Indexed: 06/22/2024] Open
Abstract
Exosomes, a category of extracellular vesicle (EV), are phospholipid bilayer structures ranging from 30 to 150 nm, produced by various organisms through the endosomal pathway. Recent studies have established the utilization of exosomes as nanocarriers for drug distribution across various therapeutic areas including cancer, acute liver injury, neuroprotection, oxidative stress, inflammation, etc. The importance of plant-derived exosomes and exosome vesicles derived from mammalian cells or milk, loaded with potent plant bioactives for various therapeutic indications are discussed along with insights into future perspectives. Moreover, this review provides a detailed understanding of exosome biogenesis, their composition, classification, stability of different types of exosomes, and different routes of administration along with the standard techniques used for isolating, purifying, and characterizing exosomes.
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Affiliation(s)
- Pooja Kathait
- Phytomedicine Research Laboratory, Department of Pharmaceutical Engineering & Technology, IIT (BHU), Varanasi, 221005, Uttar Pradesh, India
| | - Pradeep Kumar Patel
- Phytomedicine Research Laboratory, Department of Pharmaceutical Engineering & Technology, IIT (BHU), Varanasi, 221005, Uttar Pradesh, India
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Baruah H, Sarma A, Basak D, Das M. Exosome: From biology to drug delivery. Drug Deliv Transl Res 2024; 14:1480-1516. [PMID: 38252268 DOI: 10.1007/s13346-024-01515-y] [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] [Accepted: 12/27/2023] [Indexed: 01/23/2024]
Abstract
In recent years, different advancements have been observed in nanosized drug delivery systems. Factors such as stability, safety and targeting efficiency cause hindrances in the clinical translation of these synthetic nanocarriers. Therefore, researchers employed endogenous nanocarriers like exosomes as drug delivery vehicles that have an inherent ability to target more efficiently after appropriate functionalization and show higher biocompatibility and less immunogenicity and facilitate penetration through the biological barriers more quickly than the other available carriers. Exosomes are biologically derived lipid bilayer-enclosed nanosized extracellular vesicles (size ranges from 30 to 150 nm) secreted from both prokaryotic and eukaryotic cells and appears significantly in the extracellular space. These EVs (extracellular vesicles) can exist in different sources, including mammals, plants and microorganisms. Different advanced techniques have been introduced for the isolation of exosomes to overcome the existing barriers present with conventional methods. Extensive research on the application of exosomes in therapeutic delivery for treating various diseases related to central nervous system, bone, cancer, skin, etc. has been employed. Several studies are on different stages of clinical trials, and many exosomes patents have been registered.
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Affiliation(s)
- Himakshi Baruah
- Advanced Drug Delivery Laboratory, Department of Pharmaceutics, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Guwahati, 781017, Assam, India
| | - Anupam Sarma
- Advanced Drug Delivery Laboratory, Department of Pharmaceutics, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Guwahati, 781017, Assam, India.
| | - Debojeet Basak
- Advanced Drug Delivery Laboratory, Department of Pharmaceutics, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Guwahati, 781017, Assam, India
| | - Mridusmita Das
- Advanced Drug Delivery Laboratory, Department of Pharmaceutics, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Guwahati, 781017, Assam, India
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37
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Peng X, Zhang T, Liu R, Jin X. Potential in exosome-based targeted nano-drugs and delivery vehicles for posterior ocular disease treatment: from barriers to therapeutic application. Mol Cell Biochem 2024; 479:1319-1333. [PMID: 37402019 DOI: 10.1007/s11010-023-04798-w] [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: 04/13/2023] [Accepted: 06/21/2023] [Indexed: 07/05/2023]
Abstract
Posterior ocular disease, a disease that accounts for 55% of all ocular diseases, can contribute to permanent vision loss if left without treatment. Due to the special structure of the eye, various obstacles make it difficult for drugs to reach lesions in the posterior ocular segment. Therefore, the development of highly permeable targeted drugs and delivery systems is particularly important. Exosomes are a class of extracellular vesicles at 30-150 nm, which are secreted by various cells, tissues, and body fluids. They carry various signaling molecules, thus endowing them with certain physiological functions. In this review, we describe the ocular barriers and the biogenesis, isolation, and engineering of exosomes, as exosomes not only have pharmacological effects but also are good nanocarriers with targeted properties. Moreover, their biocompatibility and immunogenicity are better than synthetic nanocarriers. Most importantly, they may have the ability to pass through the blood-eye barrier. Thus, they may be developed as both targeted nano-drugs and nano-delivery vehicles for the treatment of posterior ocular diseases. We focus on the current status and potential application of exosomes as targeted nano-drugs and nano-delivery vehicles in posterior ocular diseases.
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Affiliation(s)
- Xingru Peng
- State Key Laboratory of Component‑based Chinese Medicine, Haihe Laboratory of Modern Chinese Medicine, College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Tingting Zhang
- State Key Laboratory of Component‑based Chinese Medicine, Haihe Laboratory of Modern Chinese Medicine, College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Rui Liu
- State Key Laboratory of Component‑based Chinese Medicine, Haihe Laboratory of Modern Chinese Medicine, College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
| | - Xin Jin
- Department of Health Services, Logistics University of People's Armed Police Force, Tianjin, Chenlin Road, Hedong District, Tianjin, 300162, China.
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38
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Farahzadi R, Fathi E, Valipour B, Ghaffary S. Stem cells-derived exosomes as cardiac regenerative agents. IJC HEART & VASCULATURE 2024; 52:101399. [PMID: 38584674 PMCID: PMC10990901 DOI: 10.1016/j.ijcha.2024.101399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 03/03/2024] [Accepted: 03/28/2024] [Indexed: 04/09/2024]
Abstract
Heart failure is a root cause of morbidity and mortality worldwide. Due to the limited regenerative capacity of the heart following myocardial injury, stem cell-based therapies have been considered a hopeful approach for improving cardiac regeneration. In recent years, different kinds of cell products have been investigated regarding their potential to treat patients with heart failure. Despite special attention to cell therapy and its products, therapeutic efficacy has been disappointing, and clinical application is not affordable. In the past few years, a subset of small extracellular vehicles (EVs), commonly known as "exosomes," was reported to grant regenerative and cardioprotective signals at a value similar to their donor cells. The conceptual advantage is that they may be ideally used without evoking a relevant recipient immune response or other adverse effects associated with viable cells. The evidence related to their beneficial effects in animal models of heart failure is rapidly growing. However, there is remarkable heterogeneity regarding source cells, isolation process, effective dosage, and delivery mode. This brief review will focus on the latest research and debates on regenerative potential and cardiac repair of exosomes from different sources, such as cardiac/non-cardiac stem, somatic cells, and progenitor cells. Overall, the current state of research on exosomes as an experimental therapy for heart diseases will be discussed.
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Affiliation(s)
- Raheleh Farahzadi
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Medical Philosophy and History Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ezzatollah Fathi
- Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
| | - Behnaz Valipour
- Department of Anatomical Sciences, Sarab Faculty of Medical Sciences, Sarab, Iran
- Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saba Ghaffary
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Petrovic S, Bita B, Barbinta-Patrascu ME. Nanoformulations in Pharmaceutical and Biomedical Applications: Green Perspectives. Int J Mol Sci 2024; 25:5842. [PMID: 38892030 PMCID: PMC11172476 DOI: 10.3390/ijms25115842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 05/21/2024] [Accepted: 05/24/2024] [Indexed: 06/21/2024] Open
Abstract
This study provides a brief discussion of the major nanopharmaceuticals formulations as well as the impact of nanotechnology on the future of pharmaceuticals. Effective and eco-friendly strategies of biofabrication are also highlighted. Modern approaches to designing pharmaceutical nanoformulations (e.g., 3D printing, Phyto-Nanotechnology, Biomimetics/Bioinspiration, etc.) are outlined. This paper discusses the need to use natural resources for the "green" design of new nanoformulations with therapeutic efficiency. Nanopharmaceuticals research is still in its early stages, and the preparation of nanomaterials must be carefully considered. Therefore, safety and long-term effects of pharmaceutical nanoformulations must not be overlooked. The testing of nanopharmaceuticals represents an essential point in their further applications. Vegetal scaffolds obtained by decellularizing plant leaves represent a valuable, bioinspired model for nanopharmaceutical testing that avoids using animals. Nanoformulations are critical in various fields, especially in pharmacy, medicine, agriculture, and material science, due to their unique properties and advantages over conventional formulations that allows improved solubility, bioavailability, targeted drug delivery, controlled release, and reduced toxicity. Nanopharmaceuticals have transitioned from experimental stages to being a vital component of clinical practice, significantly improving outcomes in medical fields for cancer treatment, infectious diseases, neurological disorders, personalized medicine, and advanced diagnostics. Here are the key points highlighting their importance. The significant challenges, opportunities, and future directions are mentioned in the final section.
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Affiliation(s)
- Sanja Petrovic
- Department of Chemical Technologies, Faculty of Technology, University of Nis, Bulevar Oslobodjenja 124, 16000 Leskovac, Serbia;
| | - Bogdan Bita
- Department of Electricity, Solid-State Physics and Biophysics, Faculty of Physics, University of Bucharest, 405 Atomistilor Street, P.O. Box MG-11, 077125 Magurele, Romania;
| | - Marcela-Elisabeta Barbinta-Patrascu
- Department of Electricity, Solid-State Physics and Biophysics, Faculty of Physics, University of Bucharest, 405 Atomistilor Street, P.O. Box MG-11, 077125 Magurele, Romania;
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Sharma A, Yadav A, Nandy A, Ghatak S. Insight into the Functional Dynamics and Challenges of Exosomes in Pharmaceutical Innovation and Precision Medicine. Pharmaceutics 2024; 16:709. [PMID: 38931833 PMCID: PMC11206934 DOI: 10.3390/pharmaceutics16060709] [Citation(s) in RCA: 17] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 05/13/2024] [Accepted: 05/16/2024] [Indexed: 06/28/2024] Open
Abstract
Of all the numerous nanosized extracellular vesicles released by a cell, the endosomal-originated exosomes are increasingly recognized as potential therapeutics, owing to their inherent stability, low immunogenicity, and targeted delivery capabilities. This review critically evaluates the transformative potential of exosome-based modalities across pharmaceutical and precision medicine landscapes. Because of their precise targeted biomolecular cargo delivery, exosomes are posited as ideal candidates in drug delivery, enhancing regenerative medicine strategies, and advancing diagnostic technologies. Despite the significant market growth projections of exosome therapy, its utilization is encumbered by substantial scientific and regulatory challenges. These include the lack of universally accepted protocols for exosome isolation and the complexities associated with navigating the regulatory environment, particularly the guidelines set forth by the U.S. Food and Drug Administration (FDA). This review presents a comprehensive overview of current research trajectories aimed at addressing these impediments and discusses prospective advancements that could substantiate the clinical translation of exosomal therapies. By providing a comprehensive analysis of both the capabilities and hurdles inherent to exosome therapeutic applications, this article aims to inform and direct future research paradigms, thereby fostering the integration of exosomal systems into mainstream clinical practice.
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Affiliation(s)
| | | | | | - Subhadip Ghatak
- McGowan Institute for Regenerative Medicine, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA; (A.S.); (A.Y.); (A.N.)
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Ramadan F, Saab R, Ghamloush F, Khoueiry R, Herceg Z, Gomez L, Badran B, Clezardin P, Hussein N, Cohen PA, Ghayad SE. Exosome-Mediated Paracrine Signaling Unveils miR-1246 as a Driver of Aggressiveness in Fusion-Negative Rhabdomyosarcoma. Cancers (Basel) 2024; 16:1652. [PMID: 38730605 PMCID: PMC11083369 DOI: 10.3390/cancers16091652] [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: 02/16/2024] [Revised: 04/19/2024] [Accepted: 04/19/2024] [Indexed: 05/13/2024] Open
Abstract
Rhabdomyosarcoma is a pediatric cancer associated with aggressiveness and a tendency to develop metastases. Fusion-negative rhabdomyosarcoma (FN-RMS) is the most commonly occurring subtype of RMS, where metastatic disease can hinder treatment success and decrease survival rates. RMS-derived exosomes were previously demonstrated to be enriched with miRNAs, including miR-1246, possibly contributing to disease aggressiveness. We aimed to decipher the functional impact of exosomal miR-1246 on recipient cells and its role in promoting aggressiveness. Treatment of normal fibroblasts with FN-RMS-derived exosomes resulted in a significant uptake of miR-1246 paired with an increase in cell proliferation, migration, and invasion. In turn, delivery of miR-1246-mimic lipoplexes promoted fibroblast proliferation, migration, and invasion in a similar manner. Conversely, when silencing miR-1246 in FN-RMS cells, the resulting derived exosomes demonstrated reversed effects on recipient cells' phenotype. Delivery of exosomal miR-1246 targets GSK3β and promotes β-catenin nuclear accumulation, suggesting a deregulation of the Wnt pathway, known to be important in tumor progression. Finally, a pilot clinical study highlighted, for the first time, the presence of high exosomal miR-1246 levels in RMS patients' sera. Altogether, our results demonstrate that exosomal miR-1246 has the potential to alter the tumor microenvironment of FN-RMS cells, suggesting its potential role in promoting oncogenesis.
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Affiliation(s)
- Farah Ramadan
- Université Lyon 1, Lyon, France; (F.R.); (P.C.)
- INSERM, Research Unit UMR_S1033, LyOS, Faculty of Medicine Lyon-Est, 69372 Lyon, France
- Department of Biology, Faculty of Science II, Lebanese University, Beirut 6573, Lebanon
- Laboratory of Cancer Biology and Molecular Immunology, Department of Chemistry and Biochemistry, Faculty of Science I, Lebanese University, Hadath 1103, Lebanon; (B.B.); (N.H.)
| | - Raya Saab
- Department of Pediatrics & Adolescent Medicine, American University of Beirut Medical Center, Beirut 1107, Lebanon; (R.S.); (F.G.)
- Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, Beirut 1107, Lebanon
- Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA 94304, USA
| | - Farah Ghamloush
- Department of Pediatrics & Adolescent Medicine, American University of Beirut Medical Center, Beirut 1107, Lebanon; (R.S.); (F.G.)
| | - Rita Khoueiry
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, World Health Organization, 69366 Cedex 07 Lyon, France; (R.K.); (Z.H.)
| | - Zdenko Herceg
- Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, World Health Organization, 69366 Cedex 07 Lyon, France; (R.K.); (Z.H.)
| | - Ludovic Gomez
- Laboratoire CarMeN—IRIS Team, INSERM, INRA, Université Claude Bernard Lyon-1, INSA-Lyon, Univ-Lyon, 69500 Bron, France;
| | - Bassam Badran
- Laboratory of Cancer Biology and Molecular Immunology, Department of Chemistry and Biochemistry, Faculty of Science I, Lebanese University, Hadath 1103, Lebanon; (B.B.); (N.H.)
| | - Philippe Clezardin
- Université Lyon 1, Lyon, France; (F.R.); (P.C.)
- INSERM, Research Unit UMR_S1033, LyOS, Faculty of Medicine Lyon-Est, 69372 Lyon, France
| | - Nader Hussein
- Laboratory of Cancer Biology and Molecular Immunology, Department of Chemistry and Biochemistry, Faculty of Science I, Lebanese University, Hadath 1103, Lebanon; (B.B.); (N.H.)
- Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS UMR 5286, Centre Léon Bérard, Université Lyon 1, 69008 Lyon, France
| | - Pascale A. Cohen
- Université Lyon 1, Lyon, France; (F.R.); (P.C.)
- INSERM, Research Unit UMR_S1033, LyOS, Faculty of Medicine Lyon-Est, 69372 Lyon, France
| | - Sandra E. Ghayad
- Department of Biology, Faculty of Science II, Lebanese University, Beirut 6573, Lebanon
- C2VN, INSERM 1263, INRAE 1260, Aix-Marseille University, 13005 Marseille, France
- Department of Pharmaceutical Biology, Faculty of Pharmacy, Aix-Marseille University, 27 Boulevard Jean Moulin, 13005 Marseille, France
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Raj R, Agrawal P, Bhutani U, Bhowmick T, Chandru A. Spinning with exosomes: electrospun nanofibers for efficient targeting of stem cell-derived exosomes in tissue regeneration. Biomed Mater 2024; 19:032004. [PMID: 38593835 DOI: 10.1088/1748-605x/ad3cab] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Accepted: 04/09/2024] [Indexed: 04/11/2024]
Abstract
Electrospinning technique converts polymeric solutions into nanoscale fibers using an electric field and can be used for various biomedical and clinical applications. Extracellular vesicles (EVs) are cell-derived small lipid vesicles enriched with biological cargo (proteins and nucleic acids) potential therapeutic applications. In this review, we discuss extending the scope of electrospinning by incorporating stem cell-derived EVs, particularly exosomes, into nanofibers for their effective delivery to target tissues. The parameters used during the electrospinning of biopolymers limit the stability and functional properties of cellular products. However, with careful consideration of process requirements, these can significantly improve stability, leading to longevity, effectiveness, and sustained and localized release. Electrospun nanofibers are known to encapsulate or surface-adsorb biological payloads such as therapeutic EVs, proteins, enzymes, and nucleic acids. Small EVs, specifically exosomes, have recently attracted the attention of researchers working on regeneration and tissue engineering because of their broad distribution and enormous potential as therapeutic agents. This review focuses on current developments in nanofibers for delivering therapeutic cargo molecules, with a special emphasis on exosomes. It also suggests prospective approaches that can be adapted to safely combine these two nanoscale systems and exponentially enhance their benefits in tissue engineering, medical device coating, and drug delivery applications.
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Affiliation(s)
- Ritu Raj
- Pandorum Technologies Pvt. Ltd., Bangalore 560100, Karnataka, India
| | - Parinita Agrawal
- Pandorum Technologies Pvt. Ltd., Bangalore 560100, Karnataka, India
| | - Utkarsh Bhutani
- Pandorum Technologies Pvt. Ltd., Bangalore 560100, Karnataka, India
| | - Tuhin Bhowmick
- Pandorum Technologies Pvt. Ltd., Bangalore 560100, Karnataka, India
| | - Arun Chandru
- Pandorum Technologies Pvt. Ltd., Bangalore 560100, Karnataka, India
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Wang Y, Liu Q, Sun Q, Zheng L, Jin T, Cao H, Zhu C, Li L, Gong Y, Yang F, Dong W. Exosomes from porcine serum as endogenous additive maintain function of boar sperm during liquid preservation at 17 °C in vitro. Theriogenology 2024; 219:147-156. [PMID: 38430799 DOI: 10.1016/j.theriogenology.2024.02.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 02/08/2024] [Accepted: 02/13/2024] [Indexed: 03/05/2024]
Abstract
The supplementation of sperm culture media with serum is quite common, and improves both sperm survival and motility. However, the link between serum and sperm remains poorly understood. The present study is the first investigation of the effects on sperm quality and function of endogenous porcine serum exosomes in medium used for culturing boar sperm. Scanning electron microscopy (SEM) confirmed that serum-derived exosomes from both castrated boars (cbsExos) and sows (ssExos) exhibited typical nanostructural morphology and expressed CD63, CD9, and Alix, as shown by Western blotting. At 17 °C, the progressive motility and membrane integrity of sperm were significantly increased after incubation of fresh boar semen for 7 days with cbsExos-4 (8 × 1010 particles/mL) or ssExos-16 (32 × 1010 particles/mL). Moreover, cbsExos-4 and ssExos-16 were found to be effective sperm additives, improving mitochondrial transmembrane potential (ΔΨm) and adenosine triphosphate (ATP) content, total antioxidant activity (T-AOC), superoxide dismutase (SOD) activity, and glutathione peroxidase (GPx) activity while reducing reactive oxygen species (ROS) levels, and malondialdehyde (MDA) content following preservation at 17 °C after a 5-day incubation. Both fluorescence and SEM showed that the serum exosomes bound directly to the sperm membrane, suggesting an interaction that could influence sperm-zona pellucida binding. Overall, this study provides new insights into the potential benefits of adding cbsExos and ssExos to enhance the quality of boar sperm during ambient temperature preservation, which may lead to advancements in sperm preservation strategies.
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Affiliation(s)
- Yang Wang
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Qimin Liu
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Qingfang Sun
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Lijuan Zheng
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Tianqi Jin
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Heran Cao
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Chao Zhu
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Long Li
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China
| | - Ye Gong
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China; Shaanxi Dayi Xunlong Biotechnology Co., LTD, Yangling, Shaanxi, 712100, China
| | - Fangxia Yang
- College of Forestry, Northwest A&F University, Yangling, Shaanxi, 712100, China; Biology Research Centre of Qin Mountains Wildlife, Northwest A&F University, Yangling, Shaanxi, 712100, China.
| | - Wuzi Dong
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China; Biology Research Centre of Qin Mountains Wildlife, Northwest A&F University, Yangling, Shaanxi, 712100, China.
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44
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White B, Swietach P. What can we learn about acid-base transporters in cancer from studying somatic mutations in their genes? Pflugers Arch 2024; 476:673-688. [PMID: 37999800 PMCID: PMC11006749 DOI: 10.1007/s00424-023-02876-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 10/24/2023] [Accepted: 10/30/2023] [Indexed: 11/25/2023]
Abstract
Acidosis is a chemical signature of the tumour microenvironment that challenges intracellular pH homeostasis. The orchestrated activity of acid-base transporters of the solute-linked carrier (SLC) family is critical for removing the end-products of fermentative metabolism (lactate/H+) and maintaining a favourably alkaline cytoplasm. Given the critical role of pH homeostasis in enabling cellular activities, mutations in relevant SLC genes may impact the oncogenic process, emerging as negatively or positively selected, or as driver or passenger mutations. To address this, we performed a pan-cancer analysis of The Cancer Genome Atlas simple nucleotide variation data for acid/base-transporting SLCs (ABT-SLCs). Somatic mutation patterns of monocarboxylate transporters (MCTs) were consistent with their proposed essentiality in facilitating lactate/H+ efflux. Among all cancers, tumours of uterine corpus endometrial cancer carried more ABT-SLC somatic mutations than expected from median tumour mutation burden. Among these, somatic mutations in SLC4A3 had features consistent with meaningful consequences on cellular fitness. Definitive evidence for ABT-SLCs as 'cancer essential' or 'driver genes' will have to consider microenvironmental context in genomic sequencing because bulk approaches are insensitive to pH heterogeneity within tumours. Moreover, genomic analyses must be validated with phenotypic outcomes (i.e. SLC-carried flux) to appreciate the opportunities for targeting acid-base transport in cancers.
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Affiliation(s)
- Bobby White
- Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford, OX1 3PT, UK.
| | - Pawel Swietach
- Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford, OX1 3PT, UK
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45
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Mohammadi M, Mansouri K, Mohammadi P, Pournazari M, Najafi H. Exosomes in renal cell carcinoma: challenges and opportunities. Mol Biol Rep 2024; 51:443. [PMID: 38520545 DOI: 10.1007/s11033-024-09384-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Accepted: 02/26/2024] [Indexed: 03/25/2024]
Abstract
Renal cell carcinoma (RCC) is the most common type of kidney cancer that accounts for approximately 2-3% of adult malignancies. Among the primary treatment methods for this type of cancer are surgery and targeted treatment. Still, due to less than optimal effectiveness, there are problems such as advanced distant metastasis, delayed diagnosis, and drug resistance that continue to plague patients. In recent years, therapeutic advances have increased life expectancy and effective treatment in renal cell carcinoma patients. One of these methods is the use of stem cells. Although the therapeutic effects of stem cells, especially mesenchymal stem cells, are still impressive, today, extracellular vesicles (EVs) as carrying molecules and various mediators in intercellular communications, having a central role in tumorigenesis, metastasis, immune evasion, and drug response, and on the other hand, due to its low immunogenicity and strong regulatory properties of the immune system, has received much attention from researchers and doctors. Despite the increasing interest in exosomes as the most versatile type of EVs, the heterogeneity of their efficacy presents challenges and, on the other hand, exciting opportunities for diagnostic and clinical interventions.In the upcoming article, we will review the various aspects of exosomes' effects in the prevention, treatment, and progress of renal cell carcinoma and also ways to optimize them to strengthen their positive sides.
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Affiliation(s)
- Mahan Mohammadi
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Kamran Mansouri
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Pantea Mohammadi
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mehran Pournazari
- Clinical Research Development Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Houshang Najafi
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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46
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Gai C, Pomatto MAC, Deregibus MC, Dieci M, Piga A, Camussi G. Edible Plant-Derived Extracellular Vesicles for Oral mRNA Vaccine Delivery. Vaccines (Basel) 2024; 12:200. [PMID: 38400183 PMCID: PMC10893065 DOI: 10.3390/vaccines12020200] [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: 01/05/2024] [Revised: 02/08/2024] [Accepted: 02/13/2024] [Indexed: 02/25/2024] Open
Abstract
Nucleic acid delivery through extracellular vesicles (EVs) is a well-preserved evolutionary mechanism in all life kingdoms including eukaryotes, prokaryotes, and plants. EVs naturally allow horizontal transfer of native as well as exogenous functional mRNAs, which once incorporated in EVs are protected from enzymatic degradation. This observation has prompted researchers to investigate whether EVs from different sources, including plants, could be used for vaccine delivery. Several studies using human or bacterial EVs expressing mRNA or recombinant SARS-CoV-2 proteins showed induction of a humoral and cell mediated immune response. Moreover, EV-based vaccines presenting the natural configuration of viral antigens have demonstrated advantages in conferring long-lasting immunization and lower toxicity than synthetic nanoparticles. Edible plant-derived EVs were shown to be an alternative to human EVs for vaccine delivery, especially via oral administration. EVs obtained from orange juice (oEVs) loaded with SARS-CoV-2 mRNAs protected their cargo from enzymatic degradation, were stable at room temperature for one year, and were able to trigger a SARS-CoV-2 immune response in mice. Lyophilized oEVs containing the S1 mRNA administered to rats via gavage induced a specific humoral immune response with generation of blocking antibodies, including IgA and Th1 lymphocyte activation. In conclusion, mRNA-containing oEVs could be used for developing new oral vaccines due to optimal mucosal absorption, resistance to stress conditions, and ability to stimulate a humoral and cellular immune response.
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Affiliation(s)
- Chiara Gai
- EvoBiotech s.r.l., 10148 Torino, Italy; (C.G.); (M.A.C.P.); (M.D.); (A.P.)
- Department of Medical Sciences, University of Turin, 10126 Torino, Italy;
| | - Margherita Alba Carlotta Pomatto
- EvoBiotech s.r.l., 10148 Torino, Italy; (C.G.); (M.A.C.P.); (M.D.); (A.P.)
- Department of Medical Sciences, University of Turin, 10126 Torino, Italy;
| | | | - Marco Dieci
- EvoBiotech s.r.l., 10148 Torino, Italy; (C.G.); (M.A.C.P.); (M.D.); (A.P.)
| | - Alessandro Piga
- EvoBiotech s.r.l., 10148 Torino, Italy; (C.G.); (M.A.C.P.); (M.D.); (A.P.)
| | - Giovanni Camussi
- Department of Medical Sciences, University of Turin, 10126 Torino, Italy;
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47
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Fatima S, Qaiser A, Andleeb S, Hashmi AH, Manzoor S. Navigating the brain: the role of exosomal shuttles in precision therapeutics. Front Neurol 2024; 14:1324216. [PMID: 38304326 PMCID: PMC10831691 DOI: 10.3389/fneur.2023.1324216] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 11/28/2023] [Indexed: 02/03/2024] Open
Abstract
Brain diseases have become one of the leading roots of mortality and disability worldwide, contributing a significant part of the disease burden on healthcare systems. The blood-brain barrier (BBB) is a primary physical and biological obstacle that allows only small molecules to pass through it. Its selective permeability is a significant challenge in delivering therapeutics into the brain for treating brain dysfunction. It is estimated that only 2% of the new central nervous system (CNS) therapeutic compounds can cross the BBB and achieve their therapeutic targets. Scientists are exploring various approaches to develop effective cargo delivery vehicles to promote better therapeutics targeting the brain with minimal off-target side effects. Despite different synthetic carriers, one of the natural brain cargo delivery systems, "exosomes," are now employed to transport drugs through the BBB. Exosomes are naturally occurring small extracellular vesicles (EVs) with unique advantages as a therapeutic delivery system for treating brain disorders. They have beneficial innate aspects of biocompatibility, higher stability, ability to cross BBB, low cytotoxicity, low immunogenicity, homing potential, targeted delivery, and reducing off-site target effects. In this review, we will discuss the limitations of synthetic carriers and the utilization of naturally occurring exosomes as brain-targeted cargo delivery vehicles and highlight the methods for modifying exosome surfaces and drug loading into exosomes. We will also enlist neurodegenerative disorders targeted with genetically modified exosomes for their treatment.
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Affiliation(s)
- Shaheera Fatima
- Atta-ur-Rehman School of Applied Biosciences, Healthcare Biotechnology, National University of Science and Technology, Islamabad, Pakistan
| | - Ariba Qaiser
- Atta-ur-Rehman School of Applied Biosciences, Healthcare Biotechnology, National University of Science and Technology, Islamabad, Pakistan
| | - Saadia Andleeb
- Atta-ur-Rehman School of Applied Biosciences, Industrial Biotechnology, National University of Science and Technology, Islamabad, Pakistan
| | | | - Sobia Manzoor
- Atta-ur-Rehman School of Applied Biosciences, Healthcare Biotechnology, National University of Science and Technology, Islamabad, Pakistan
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48
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Martino E, D’Onofrio N, Balestrieri A, Colloca A, Anastasio C, Sardu C, Marfella R, Campanile G, Balestrieri ML. Dietary Epigenetic Modulators: Unravelling the Still-Controversial Benefits of miRNAs in Nutrition and Disease. Nutrients 2024; 16:160. [PMID: 38201989 PMCID: PMC10780859 DOI: 10.3390/nu16010160] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 12/29/2023] [Accepted: 12/30/2023] [Indexed: 01/12/2024] Open
Abstract
In the context of nutrient-driven epigenetic alterations, food-derived miRNAs can be absorbed into the circulatory system and organs of recipients, especially humans, and potentially contribute to modulating health and diseases. Evidence suggests that food uptake, by carrying exogenous miRNAs (xenomiRNAs), regulates the individual miRNA profile, modifying the redox homeostasis and inflammatory conditions underlying pathological processes, such as type 2 diabetes mellitus, insulin resistance, metabolic syndrome, and cancer. The capacity of diet to control miRNA levels and the comprehension of the unique characteristics of dietary miRNAs in terms of gene expression regulation show important perspectives as a strategy to control disease susceptibility via epigenetic modifications and refine the clinical outcomes. However, the absorption, stability, availability, and epigenetic roles of dietary miRNAs are intriguing and currently the subject of intense debate; additionally, there is restricted knowledge of their physiological and potential side effects. Within this framework, we provided up-to-date and comprehensive knowledge on dietary miRNAs' potential, discussing the latest advances and controversial issues related to the role of miRNAs in human health and disease as modulators of chronic syndromes.
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Affiliation(s)
- Elisa Martino
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (E.M.); (A.C.); (C.A.); (M.L.B.)
| | - Nunzia D’Onofrio
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (E.M.); (A.C.); (C.A.); (M.L.B.)
| | - Anna Balestrieri
- Food Safety Department, Istituto Zooprofilattico Sperimentale del Mezzogiorno, 80055 Portici, Italy;
| | - Antonino Colloca
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (E.M.); (A.C.); (C.A.); (M.L.B.)
| | - Camilla Anastasio
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (E.M.); (A.C.); (C.A.); (M.L.B.)
| | - Celestino Sardu
- Department of Advanced Clinical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (C.S.); (R.M.)
| | - Raffaele Marfella
- Department of Advanced Clinical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (C.S.); (R.M.)
| | - Giuseppe Campanile
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy;
| | - Maria Luisa Balestrieri
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (E.M.); (A.C.); (C.A.); (M.L.B.)
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49
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Zhou X, Jia Y, Mao C, Liu S. Small extracellular vesicles: Non-negligible vesicles in tumor progression, diagnosis, and therapy. Cancer Lett 2024; 580:216481. [PMID: 37972701 DOI: 10.1016/j.canlet.2023.216481] [Citation(s) in RCA: 17] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 10/26/2023] [Accepted: 11/04/2023] [Indexed: 11/19/2023]
Abstract
Small extracellular vesicles (sEVs) such as exosomes are nanoscale membranous particles (<200 nm) that have emerged as crucial targets for liquid biopsy and as promising drug delivery vehicles. They play a significant role in tumor progression as intercellular messengers. They can serve as biomarkers for tumor diagnosis and as drug carriers for cancer treatment. This article reviews recent studies on sEVs in oncology and explores their potential as biomarkers and drug delivery vehicles. Following tumorigenesis, sEVs in the tumor microenvironment (TME) and circulatory system undergo modifications to regulate various events in the TME, including angiogenesis, epithelial-mesenchymal transition (EMT), and tumor immunity, with either pro- or anti-tumor effects. sEVs have been investigated for use as diagnostic and prognostic biomarkers for a variety of tumors, including lung cancer, melanoma, breast cancer, prostate cancer, and hepatocellular carcinoma. sEVs can be used for cancer therapy by packaging drugs or proteins into them through pre- and post-isolation modification techniques. The clinical trials of sEVs as biomarkers and drug carriers are also summarized. Finally, the challenges in the use of sEVs are described and the possible approaches to tackling them are suggested. Overall, sEVs will advance the precision cancer medicine and has shown great potential in clinical applications.
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Affiliation(s)
- Xinru Zhou
- Department of Laboratory Diagnostics, Changhai Hospital, Navy Military Medical University, Shanghai, China
| | - Yin Jia
- Department of Laboratory Diagnostics, Changhai Hospital, Navy Military Medical University, Shanghai, China
| | - Chuanbin Mao
- Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China; School of Materials Science & Engineering, Zhejiang University, Hangzhou, Zhejiang, China.
| | - Shanrong Liu
- Department of Laboratory Diagnostics, Changhai Hospital, Navy Military Medical University, Shanghai, China.
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50
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Hormozi A, Hasanzadeh S, Ebrahimi F, Daei N, Hajimortezayi Z, Mehdizadeh A, Zamani M. Treatment with Exosomes Derived from Mesenchymal Stem Cells: A New Window of Healing Science in Regenerative Medicine. Curr Stem Cell Res Ther 2024; 19:879-893. [PMID: 37622719 DOI: 10.2174/1574888x18666230824165014] [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: 03/11/2023] [Revised: 07/07/2023] [Accepted: 07/12/2023] [Indexed: 08/26/2023]
Abstract
Many studies have been conducted on the potential applications of mesenchymal stem cells (MSCs) over recent years due to their growing importance in regenerative medicine. Exosomes are considered cargos capable of transporting proteins, peptides, lipids, mRNAs, and growth factors. MSCsderived exosomes are also involved in the prevention or treatment of a variety of diseases, including cardiovascular diseases, neurological diseases, skin disorders, lung diseases, osteoarthritis, damaged tissue repair, and other diseases. This review attempted to summarize the importance of employing MSCs in regenerative medicine by gathering and evaluating information from current literature. The role of MSCs and the potential applications of MSCs-derived exosomes have also been discussed.
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Affiliation(s)
- Arezoo Hormozi
- Student Research Committee, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Sajedeh Hasanzadeh
- Student Research Committee, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Faezeh Ebrahimi
- Student Research Committee, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Narges Daei
- Student Research Committee, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Zahra Hajimortezayi
- Student Research Committee, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Amir Mehdizadeh
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Majid Zamani
- Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
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