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Park KS, Lässer C, Lötvall J. Extracellular vesicles and the lung: from disease pathogenesis to biomarkers and treatments. Physiol Rev 2025; 105:1733-1821. [PMID: 40125970 DOI: 10.1152/physrev.00032.2024] [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: 08/14/2024] [Revised: 10/14/2024] [Accepted: 03/12/2025] [Indexed: 03/25/2025] Open
Abstract
Nanosized extracellular vesicles (EVs) are released by all cells to convey cell-to-cell communication. EVs, including exosomes and microvesicles, carry an array of bioactive molecules, such as proteins and RNAs, encapsulated by a membrane lipid bilayer. Epithelial cells, endothelial cells, and various immune cells in the lung contribute to the pool of EVs in the lung microenvironment and carry molecules reflecting their cellular origin. EVs can maintain lung health by regulating immune responses, inducing tissue repair, and maintaining lung homeostasis. They can be detected in lung tissues and biofluids such as bronchoalveolar lavage fluid and blood, offering information about disease processes, and can function as disease biomarkers. Here, we discuss the role of EVs in lung homeostasis and pulmonary diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, pulmonary fibrosis, and lung injury. The mechanistic involvement of EVs in pathogenesis and their potential as disease biomarkers are discussed. Finally, the pulmonary field benefits from EVs as clinical therapeutics in severe pulmonary inflammatory disease, as EVs from mesenchymal stem cells attenuate severe respiratory inflammation in multiple clinical trials. Further, EVs can be engineered to carry therapeutic molecules for enhanced and broadened therapeutic opportunities, such as the anti-inflammatory molecule CD24. Finally, we discuss the emerging opportunity of using different types of EVs for treating severe respiratory conditions.
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Affiliation(s)
- Kyong-Su Park
- Krefting Research Centre, Institute of Medicine at the Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Cecilia Lässer
- Krefting Research Centre, Institute of Medicine at the Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Jan Lötvall
- Krefting Research Centre, Institute of Medicine at the Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
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Lv K, Gao J, Yang L, Yuan X. The role of mesenchymal stem cell‑derived exosomes in asthma (Review). Mol Med Rep 2025; 31:166. [PMID: 40242981 PMCID: PMC12012432 DOI: 10.3892/mmr.2025.13531] [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: 03/17/2025] [Indexed: 04/18/2025] Open
Abstract
Asthma is a chronic respiratory disorder characterized by persistent inflammation, airway hyper‑responsiveness and remodeling, leading to notable morbidity and decreased quality of life for patients. Mesenchymal stem cells (MSCs) have potential in regenerative medicine due to their potent immunomodulatory properties and anti‑inflammatory effects. The therapeutic benefits of MSCs are largely mediated by secreted exosomes that facilitate intercellular communication by transferring bioactive molecules, including proteins, lipids and microRNAs. The present review explores the therapeutic potential of MSC‑derived exosomes in asthma, highlighting their ability to modulate key pathological mechanisms underlying the disease.
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Affiliation(s)
- Kaiying Lv
- Department of Graduate Studies, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P.R. China
| | - Jiawei Gao
- Department of Graduate Studies, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P.R. China
| | - Liuxin Yang
- Department of Graduate Studies, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P.R. China
| | - Xingxing Yuan
- Department of Graduate Studies, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, P.R. China
- Department of Gastroenterology, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, Heilongjiang 150006, P.R. China
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Liu C, Huang X, Li S, Ji W, Luo T, Liang J, Lv Y. M2 macrophage-derived exosomes reverse TGF-β1-induced epithelial mesenchymal transformation in BEAS-2B cells via the TGF-βRI/Smad2/3 signaling pathway. Eur J Med Res 2025; 30:271. [PMID: 40211426 PMCID: PMC11987241 DOI: 10.1186/s40001-025-02516-4] [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: 11/11/2024] [Accepted: 03/26/2025] [Indexed: 04/13/2025] Open
Abstract
INTRODUCTION Airway remodeling in bronchial asthma can be inhibited by disrupting the epithelial mesenchymal transition (EMT) of activated airway epithelial cells. Exosomes, as key mediators of intercellular communication, have been implicated in the pathophysiology of asthma-related airway inflammation, remodeling, and hyperresponsiveness. This study aimed to investigate the role of M2 macrophage-derived exosomes (M2φ-exos) in modulating TGF-β1-induced EMT in airway epithelial (BEAS-2B) cells and elucidate the underlying molecular mechanism, if any. METHODS THP-1 cells were induced to differentiate into M2 macrophages via phorbol 12-myristate 13-acetate (PMA) and IL-4. Exosomes were subsequently isolated and purified via ultracentrifugation. M2φ-exos expression was characterized by protein marker levels, transmission electron microscopy imaging, and nanoparticle tracking analysis. TGF-β1-induced BEAS-2B cells were exposed to M2φ-exos to determine the latter's effects. RESULTS THP-1 cells were successfully differentiated into M2 macrophages, as confirmed by in vitro flow cytometry. The isolated exosomes presented typical cup-shaped structures and expressed CD81 and TSG101. TGF-β1 induction altered the morphological characteristics of BEAS-2B cells and activated the TGF-βRI/Smad2/3 signaling pathway, leading to increased expression of Snail, Vimentin and Collagen 1 and decreased expression of E-cadherin. After exosome or SB431542 induction, TGF-β1-induced EMT was reversed. GW4869, an exosome release inhibitor, exhibited the ability to block the beneficial effects of exosomes. CONCLUSION M2Φ-exos inhibited EMT in BEAS-2B cells through the TGF-βRI/Smad2/3 signaling pathway. This novel insight into the role of M2Φ-exos in modulating EMT may have important implications for the beneficial effects of asthma, particularly in addressing airway remodeling.
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Affiliation(s)
- Chao Liu
- Department of Respiratory and Critical Care Medicine, Zhongshan People's Hospital, Zhongshan, Guangdong, China
| | - Xiaolin Huang
- Dental Implant and Restoration Centre, Zhongshan Stomatological Hospital, Zhongshan, Guangdong, China
| | - Siqi Li
- Department of Respiratory and Critical Care Medicine, Zhongshan People's Hospital, Zhongshan, Guangdong, China
| | - Wentao Ji
- Department of Respiratory and Critical Care Medicine, Zhongshan People's Hospital, Zhongshan, Guangdong, China
| | - Tian Luo
- Department of Respiratory and Critical Care Medicine, Zhongshan People's Hospital, Zhongshan, Guangdong, China
| | - Jianping Liang
- Department of Respiratory and Critical Care Medicine, Zhongshan People's Hospital, Zhongshan, Guangdong, China.
| | - Yanhua Lv
- Department of Respiratory and Critical Care Medicine, Shunde Hospital, Southern Medical University (the First People'S Hospital of Shunde), Foshan, Guangdong, China.
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Cheema NA, Castagna A, Ambrosani F, Argentino G, Friso S, Zurlo M, Beri R, Maule M, Vaia R, Senna G, Caminati M. Extracellular Vesicles in Asthma: Intercellular Cross-Talk in TH2 Inflammation. Cells 2025; 14:542. [PMID: 40214495 PMCID: PMC11989134 DOI: 10.3390/cells14070542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 03/26/2025] [Accepted: 03/31/2025] [Indexed: 04/14/2025] Open
Abstract
Asthma is a complex, multifactorial inflammatory disorder of the airways, characterized by recurrent symptoms and variable airflow obstruction. So far, two main asthma endotypes have been identified, type 2 (T2)-high or T2-low, based on the underlying immunological mechanisms. Recently, extracellular vesicles (EVs), particularly exosomes, have gained increasing attention due to their pivotal role in intercellular communication and distal signaling modulation. In the context of asthma pathobiology, an increasing amount of experimental evidence suggests that EVs secreted by eosinophils, mast cells, dendritic cells, T cells, neutrophils, macrophages, and epithelial cells contribute to disease modulation. This review explores the role of EVs in profiling the molecular signatures of T2-high and T2-low asthma, offering novel perspectives on disease mechanisms and potential therapeutic targets.
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Affiliation(s)
- Naila Arif Cheema
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
| | - Annalisa Castagna
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
| | - Francesca Ambrosani
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
| | - Giuseppe Argentino
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
| | - Simonetta Friso
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
| | - Marco Zurlo
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
- Allergy Unit and Asthma Center, Verona Integrated University Hospital, 37126 Verona, Italy
| | - Ruggero Beri
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
| | - Matteo Maule
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
- Allergy Unit and Asthma Center, Verona Integrated University Hospital, 37126 Verona, Italy
| | - Rachele Vaia
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
- Allergy Unit and Asthma Center, Verona Integrated University Hospital, 37126 Verona, Italy
| | - Gianenrico Senna
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
- Allergy Unit and Asthma Center, Verona Integrated University Hospital, 37126 Verona, Italy
| | - Marco Caminati
- Department of Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy; (N.A.C.); (M.Z.); (R.V.); (G.S.) (A.C.); (F.A.); (G.A.); (S.F.); (R.B.)
- Allergy Unit and Asthma Center, Verona Integrated University Hospital, 37126 Verona, Italy
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Zubair M, Abouelnazar FA, Iqbal MA, Pan J, Zheng X, Chen T, Shen W, Yin J, Yan Y, Liu P, Mao F, Chu Y. Mesenchymal stem cell-derived exosomes as a plausible immunomodulatory therapeutic tool for inflammatory diseases. Front Cell Dev Biol 2025; 13:1563427. [PMID: 40129569 PMCID: PMC11931156 DOI: 10.3389/fcell.2025.1563427] [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: 01/20/2025] [Accepted: 02/21/2025] [Indexed: 03/26/2025] Open
Abstract
Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), especially, exosomes are considered to have diverse therapeutic effects for various significant diseases. MSC-derived exosomes (MSCex) offer substantial advantages over MSCs due to their long-term preservation, stability, absence of nuclei and fewer adverse effects such as infusion toxicity, thereby paving the way towards regenerative medicine and cell-free therapeutics. These exosomes harbor several cellular contents such as DNA, RNA, lipids, metabolites, and proteins, facilitating drug delivery and intercellular communication. MSCex have the ability to immunomodulate and trigger the anti-inflammatory process hence, playing a key role in alleviating inflammation and enhancing tissue regeneration. In this review, we addressed the anti-inflammatory effects of MSCex and the underlying immunomodulatory pathways. Moreover, we discussed the recent updates on MSCex in treating specific inflammatory diseases, including arthritis, inflammatory bowel disease, inflammatory eye diseases, and respiratory diseases such as asthma and acute respiratory distress syndrome (ARDS), as well as neurodegenerative and cardiac diseases. Finally, we highlighted the challenges in using MSCex as the successful therapeutic tool and discussed future perspectives.
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Affiliation(s)
- Muhammad Zubair
- Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu University, Changzhou, China
- Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu University, Changzhou, China
| | - Fatma A. Abouelnazar
- Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu University, Changzhou, China
- Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu University, Changzhou, China
- Faculty of Applied Health Sciences Technology, Pharos University, Alexandria, Egypt
| | | | - Jingyun Pan
- Department of Traditional Chinese Medicine, Wujin Hospital Affiliated with Jiangsu University, Changzhou, China
| | - Xuwen Zheng
- Department of Emergency, Wujin Hospital Affiliated With Jiangsu University, Changzhou, China
| | - Tao Chen
- Department of Gastroenterology, Wujin Hospital Affiliated With Jiangsu University, Changzhou, China
| | - Wenming Shen
- Department of Emergency, Wujin Hospital Affiliated With Jiangsu University, Changzhou, China
| | - Jinnan Yin
- Department of Emergency, Wujin Hospital Affiliated With Jiangsu University, Changzhou, China
| | - Yongmin Yan
- Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu University, Changzhou, China
| | - Pengjun Liu
- Department of Gastroenterology, Wujin Hospital Affiliated With Jiangsu University, Changzhou, China
| | - Fei Mao
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Ying Chu
- Wujin Clinical College, Xuzhou Medical University, Changzhou, China
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
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Chen QH, Zheng JY, Wang DC. Asthma and stem cell therapy. World J Stem Cells 2025; 17:103599. [DOI: 10.4252/wjsc.v17.i2.103599] [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: 11/28/2024] [Revised: 12/23/2024] [Accepted: 02/05/2025] [Indexed: 02/24/2025] Open
Abstract
The global incidence of asthma, a leading respiratory disorder affecting more than 235 million people, has dramatically increased in recent years. Characterized by chronic airway inflammation and an imbalanced response to airborne irritants, this chronic condition is associated with elevated levels of inflammatory factors and symptoms such as dyspnea, cough, wheezing, and chest tightness. Conventional asthma therapies, such as corticosteroids, long-acting β-agonists, and anti-inflammatory agents, often evoke diverse adverse reactions and fail to reduce symptoms and hospitalization rates over the long term effectively. These limitations have prompted researchers to explore innovative therapeutic strategies, including stem cell-related interventions, offering hope to those afflicted with this incurable disease. In this review, we describe the characteristics of stem cells and critically assess the potential and challenges of stem cell-based therapies to improve disease management and treatment outcomes for asthma and other diseases.
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Affiliation(s)
- Qiong-Hua Chen
- Department of Respiratory Medicine, Quanzhou Women’s and Children’s Hospital, Clinical Medical College of Fujian Medical University, Quanzhou 362000, Fujian Province, China
| | - Jing-Yang Zheng
- Department of Respiratory Medicine, Quanzhou Women’s and Children’s Hospital, Clinical Medical College of Fujian Medical University, Quanzhou 362000, Fujian Province, China
| | - Da-Chun Wang
- The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Medical School at Houston, Houston, TX 77030, United States
- Stem Cell Laboratory, Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian Province, China
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Luo X, Wang Y, Mao Y, Xu X, Gu W, Li W, Mao C, Zheng T, Dong L. Nebulization of Hypoxic hUCMSC-EVs Attenuates Airway Epithelial Barrier Defects in Chronic Asthma Mice by Transferring CAV-1. Int J Nanomedicine 2024; 19:10941-10959. [PMID: 39493276 PMCID: PMC11531287 DOI: 10.2147/ijn.s476151] [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: 04/29/2024] [Accepted: 10/19/2024] [Indexed: 11/05/2024] Open
Abstract
Background Nebulization of hypoxic human umbilical cord mesenchymal stem cell-derived extracellular vesicles (Hypo-EVs) can suppress airway inflammation and remodeling in a chronic asthmatic mouse; however, the exact mechanism remains unclear. Recently, airway epithelial barrier defects have been regarded as crucial therapeutic targets in asthma. The aim of this study was to investigate whether and how Hypo-EVs protect against the disruption of the airway epithelial barrier under asthmatic conditions. Methods The therapeutic effects of Hypo-EVs on airway epithelial barrier defects were evaluated in ovalbumin (OVA)-induced asthmatic mice and in IL-4 and IL-13-induced HBE135-E6E7 cell models by detecting cell monolayer leakage and junctional protein expression. The protein levels in Hypo-EVs were determined by Western blotting, and a gene knockdown approach was used to investigate the biofactors in Hypo-EVs. Results Nebulization of Hypo-EVs directly alleviated airway epithelial barrier defects in asthmatic mice, as evidenced by colocalization with bronchial epithelial cells, decreased albumin concentration, and increased ZO-1 and E-cadherin expression. In vitro, Hypo-EV treatment dramatically rescued the increase in airway cell permeability, and upregulated the ZO-1 and E-cadherin protein expressions. Based on WB analysis, we found that caveolin-1 (CAV-1) was strongly enriched in Hypo-EVs. The knockdown of CAV-1 protein levels in Hypo-EVs significantly impaired Hypo-EV-mediated barrier protection in vitro and in vivo. Moreover, CAV-1 knockdown significantly abolished the beneficial effects of Hypo-EVs on airway inflammation and remodeling in asthmatic mice. In addition, we showed that IL-4/IL-13-induced airway epithelial barrier defects were mainly related to activation of STAT6 phosphorylation (p-STAT6), and overexpression of CAV-1 or Hypo-EV treatment inhibited the levels of p-STAT6 in IL-4/IL-13-induced HBE135-E6E7 cells. Conclusion Nebulization of Hypo-EVs can attenuate airway epithelial barrier defects in asthma by delivering CAV-1 to inhibit p-STAT6 expression and may be used to treat other barrier defect diseases.
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Affiliation(s)
- Xinkai Luo
- Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China
| | - Ying Wang
- Department of Respiratory Diseases, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, Jiangsu, People’s Republic of China
| | - Yufei Mao
- Department of Ultrasound Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China
| | - Xiaowei Xu
- Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China
- Department of Laboratory Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, People’s Republic of China
| | - Weifeng Gu
- Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China
| | - Wen Li
- Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China
| | - Chaoming Mao
- Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China
| | - Tingting Zheng
- Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China
| | - Liyang Dong
- Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China
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Jadamba B, Jin Y, Lee H. Harmonising cellular conversations: decoding the vital roles of extracellular vesicles in respiratory system intercellular communications. Eur Respir Rev 2024; 33:230272. [PMID: 39537245 PMCID: PMC11558538 DOI: 10.1183/16000617.0272-2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 08/22/2024] [Indexed: 11/16/2024] Open
Abstract
Extracellular vesicles (EVs) released by various cells play crucial roles in intercellular communication within the respiratory system. This review explores the historical context and significance of research into extracellular vesicles. Categorised into exosomes (sized 30-150 nm), microvesicles (sized 50-1000 nm) and apoptotic bodies (sized 500-2000nm), based on their generation mechanisms, extracellular vesicles carry diverse cargoes of biomolecules, including proteins, lipids and nucleic acids. Respiratory ailments are the primary contributors to both mortality and morbidity across various populations globally, significantly impacting public health. Recent studies have underscored the pivotal role of extracellular vesicles, particularly their cargo content, in mediating intercellular communication between lung cells in respiratory diseases. This comprehensive review provides insights into extracellular vesicle mechanisms and emphasises their significance in major respiratory conditions, including acute lung injury, COPD, pulmonary hypertension, pulmonary fibrosis, asthma and lung cancer.
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Affiliation(s)
- Budjav Jadamba
- Department of Biology and Chemistry, Changwon National University, Changwon, Korea
| | - Yang Jin
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
| | - Heedoo Lee
- Department of Biology and Chemistry, Changwon National University, Changwon, Korea
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Liu X, Gao J, Yang L, Yuan X. Roles of Exosomal miRNAs in Asthma: Mechanisms and Applications. J Asthma Allergy 2024; 17:935-947. [PMID: 39376731 PMCID: PMC11457472 DOI: 10.2147/jaa.s485910] [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: 07/07/2024] [Accepted: 09/15/2024] [Indexed: 10/09/2024] Open
Abstract
Asthma is a chronic inflammatory disorder of the airways, characterized by a complex interplay of genetic, environmental, and immunological factors that contribute to its onset and progression. Recent advances in researches have illuminated the critical role of exosomal microRNAs (miRNAs) in the pathogenesis and development of asthma. Exosomes are nano-sized extracellular vesicles that facilitate intercellular communication by transporting a variety of bioactive molecules, including miRNAs, and play a crucial role in regulating gene expression and immune responses, which are central to the inflammatory processes underlying asthma. Exosomal miRNAs are emerging as key players in asthma due to their involvement in various aspects of the disease, including the regulation of inflammation, airway hyperresponsiveness, and remodeling. Their ability to influence the behavior of target cells and tissues makes them valuable both as diagnostic biomarkers and as potential therapeutic targets. This review aims to provide a comprehensive overview of the biogenesis of exosomes, the functional roles of exosomal miRNAs in asthma, and their clinical potential. It will explore the mechanisms by which these miRNAs contribute to asthma pathophysiology, discuss their utility in diagnosing and monitoring the disease, and highlight ongoing research efforts to harness their therapeutic potential.
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Affiliation(s)
- Xiaoxue Liu
- Department of Paediatrics, Harbin Hospital of Traditional Chinese Medicine, Harbin, 150010, People’s Republic of China
| | - Jiawei Gao
- Heilongjiang University of Chinese Medicine, Harbin, 150040, People’s Republic of China
| | - Liuxin Yang
- Heilongjiang University of Chinese Medicine, Harbin, 150040, People’s Republic of China
| | - Xingxing Yuan
- Heilongjiang University of Chinese Medicine, Harbin, 150040, People’s Republic of China
- Department of Gastroenterology, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, 150006, People’s Republic of China
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10
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Yu H, Zhu G, Qin Q, Wang X, Guo X, Gu W. Mesenchymal Stromal Cell Therapy Alleviates Ovalbumin-Induced Chronic Airway Remodeling by Suppressing M2 Macrophage Polarization. Inflammation 2024; 47:1298-1312. [PMID: 38316671 DOI: 10.1007/s10753-024-01977-9] [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: 12/14/2023] [Revised: 01/15/2024] [Accepted: 01/16/2024] [Indexed: 02/07/2024]
Abstract
Chronic asthma is characterized by airway hyperresponsiveness, inflammation, and remodeling. Previous studies have shown that mesenchymal stromal/stem cells (MSCs) exert anti-inflammatory effects on asthma via regulation of the immune cells. However, the therapeutic mechanism of MSCs, especially the mechanism of airway remodeling in chronic asthma, remains to be elucidated. Here, we aimed to investigate the therapeutic effect of MSCs on airway remodeling in chronic asthma and explored the mechanisms by analyzing the polarization phenotype of macrophages in the lungs. We established a mouse model of chronic asthma induced by ovalbumin (OVA) and evaluated the effect of MSCs on airway remodeling. The data showed that MSCs treatment before the challenge exerted protective effects on OVA-induced chronic asthma, i.e., decreased the inflammatory cell infiltration, Th2 cytokine levels, subepithelial extracellular matrix deposition, and transforming growth factor β (TGF-β)/Smad signaling. Additionally, we found that MSCs treatment markedly suppressed macrophage M2 polarization in lung tissue. At the same time, MSCs treatment inhibited NF-κB p65 nuclear translocation, ER stress, and oxidative stress in the OVA-induced chronic allergic airway remodeling mice model. In conclusion, these results demonstrated that MSCs treatment prevents OVA-induced chronic airway remodeling by suppressing macrophage M2 polarization, which may be associated with the dual inhibition of ER stress and oxidative stress. This discovery may provide a new theoretical basis for the future clinical application of MSCs.
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Affiliation(s)
- Haiyang Yu
- Department of Respiratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 KongJiang Road, Shanghai, 200092, China
| | - Guiyin Zhu
- Department of Respiratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 KongJiang Road, Shanghai, 200092, China
| | - Qiangqiang Qin
- Department of Respiratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 KongJiang Road, Shanghai, 200092, China
| | - Xueting Wang
- Department of Respiratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 KongJiang Road, Shanghai, 200092, China
| | - Xuejun Guo
- Department of Respiratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 KongJiang Road, Shanghai, 200092, China.
| | - Wen Gu
- Department of Respiratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 KongJiang Road, Shanghai, 200092, China.
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11
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Chen S, Gao J, Zhang T. From mesenchymal stem cells to their extracellular vesicles: Progress and prospects for asthma therapy. Asian J Pharm Sci 2024; 19:100942. [PMID: 39253613 PMCID: PMC11382190 DOI: 10.1016/j.ajps.2024.100942] [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: 04/22/2023] [Revised: 12/18/2023] [Accepted: 05/20/2024] [Indexed: 09/11/2024] Open
Abstract
Asthma is a widespread public health concern, with an increasing incidence. Despite the implementation of current treatment strategies, asthma control, particularly for severe cases, remains suboptimal. Recent research has revealed the encouraging prospects of extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) as a viable therapeutic option for alleviating asthma symptoms. Therefore, the present review aims to provide an overview of the current progress and the therapeutic mechanisms of using MSC-derived EVs (MSC-EVs) for asthma treatment. Additionally, different administration approaches for EVs and their impacts on biodistribution and the curative outcomes of EVs are summarized. Notably, the potential benefits of nebulized inhalation of MSC-EVs are addressed. Also, the possibilities and challenges of using MSC-EVs for asthma treatment in clinics are highlighted. Overall, this review is intended to give new insight into the utilization of MSC-EVs as a potential biological drug for asthma treatment.
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Affiliation(s)
- Shihan Chen
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
- Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Jianqing Gao
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
- Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
- State Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou 310058, China
| | - Tianyuan Zhang
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
- Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
- State Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou 310058, China
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Firouzabadi SR, Mohammadi I, Ghafourian K, Kiani A, Hashemi SM. Mesenchymal Stem Cell-Derived Extracellular Vesicle Therapy for Asthma in Murine Models: A Systematic Review and Meta-analysis. Stem Cell Rev Rep 2024; 20:1162-1183. [PMID: 38492133 DOI: 10.1007/s12015-024-10704-8] [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] [Accepted: 02/24/2024] [Indexed: 03/18/2024]
Abstract
BACKGROUND Asthma is a common disease, and among the most predominant causes of the years lived with disability. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising avenue for asthma management. The objective of this study is to perform a systematic review and meta-analysis of pre-clinical studies investigating the therapeutic use of MSC-EVs in murine models of asthma. METHODS A systematic search of electronic databases was performed. Meta-analyses were conducted on broncho-alveolar lavage fluid (BALF) cells and cytokines, as well as airway hyper-responsiveness Penh values and histological staining scores to determine the efficacy of MSC-EVs-based therapy, comparing treated rodents with untreated ones. BALF IL-4, BALF total cells, and BALF eosinophils were chosen as the primary outcomes, while airway hyper-responsiveness Penh values, BALF cytokines excluding IL-4, and histological staining scores were chosen as secondary outcomes. RESULTS A total of 19 eligible studies were included in the current systematic review, with 9 assessing BALF IL-4, 11 assessing BALF total cells, and 10 assessing BALF eosinophils. Pooled Hedges' g (p-value) for each outcome was - 4.407 (< 0.001), -4.976 (< 0.001), and - 4.071 (< 0.001), showing that MSC-EVs therapy inhibits asthma pathology. Changes in secondary outcomes also indicated a reduction in inflammation, goblet cell hyperplasia, and airway hyper-responsiveness. Subgroup analyses did not reveal significant disparities between the type of rodents and administration routes, and meta-regressions were only significant for MSC-EVs source and dose in the IL-4 meta-analysis, and for administration frequency and time from the last challenge to sacrifice in the BALF total cell meta-analysis. CONCLUSION This review highlights the current pre-clinical evidence of MSC-EVs therapy for asthma and finds its application ameliorates multiple aspects of asthma's pathology. We further underline the importance of MSC-EVs source, dose, administration frequency, and timing on the therapeutic effect and warrant further investigation and clinical translation to assess the best treatment regimen and to gauge the efficacy of EV therapy in human asthma cases.
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Affiliation(s)
- Shahryar Rajai Firouzabadi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Koodakyar street, Daneshjoo Boulevard, Tehran, Iran.
- Tehran Lung Research and Developmental Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Ida Mohammadi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Koodakyar street, Daneshjoo Boulevard, Tehran, Iran
- Tehran Lung Research and Developmental Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kiana Ghafourian
- School of Medicine, Shahid Beheshti University of Medical Sciences, Koodakyar street, Daneshjoo Boulevard, Tehran, Iran
| | - Arda Kiani
- Tehran Lung Research and Developmental Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Mahmoud Hashemi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Li M, Jia D, Li J, Li Y, Wang Y, Wang Y, Xie W, Chen S. Scutellarin Alleviates Ovalbumin-Induced Airway Remodeling in Mice and TGF-β-Induced Pro-fibrotic Phenotype in Human Bronchial Epithelial Cells via MAPK and Smad2/3 Signaling Pathways. Inflammation 2024; 47:853-873. [PMID: 38168709 PMCID: PMC11147947 DOI: 10.1007/s10753-023-01947-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 12/07/2023] [Accepted: 12/08/2023] [Indexed: 01/05/2024]
Abstract
Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling. Epithelial-mesenchymal transition (EMT) is an essential player in these alterations. Scutellarin is isolated from Erigeron breviscapus. Its vascular relaxative, myocardial protective, and anti-inflammatory effects have been well established. This study was designed to detect the biological roles of scutellarin in asthma and its related mechanisms. The asthma-like conditions were induced by ovalbumin challenges. The airway resistance and dynamic compliance were recorded as the results of AHR. Bronchoalveolar lavage fluid (BALF) was collected and processed for differential cell counting. Hematoxylin and eosin staining, periodic acid-Schiff staining, and Masson staining were conducted to examine histopathological changes. The levels of asthma-related cytokines were measured by enzyme-linked immunosorbent assay. For in vitro analysis, the 16HBE cells were stimulated with 10 ng/mL transforming growth beta-1 (TGF-β1). Cell migration was estimated by Transwell assays and wound healing assays. E-cadherin, N-cadherin, and α-smooth muscle actin (α-SMA) were analyzed by western blotting, real-time quantitative polymerase chain reaction, immunofluorescence staining, and immunohistochemistry staining. The underlying mechanisms of the mitogen-activated protein kinase (MAPK) and Smad pathways were investigated by western blotting. In an ovalbumin-induced asthmatic mouse model, scutellarin suppressed inflammation and inflammatory cell infiltration into the lungs and attenuated AHR and airway remodeling. Additionally, scutellarin inhibited airway EMT (upregulated E-cadherin level and downregulated N-cadherin and α-SMA) in ovalbumin-challenged asthmatic mice. For in vitro analysis, scutellarin prevented the TGF-β1-induced migration and EMT in 16HBE cells. Mechanistically, scutellarin inhibits the phosphorylation of Smad2, Smad3, ERK, JNK, and p38 in vitro and in vivo. In conclusion, scutellarin can inactivate the Smad/MAPK pathways to suppress the TGF-β1-stimulated epithelial fibrosis and EMT and relieve airway inflammation and remodeling in asthma. This study provides a potential therapeutic strategy for asthma.
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Affiliation(s)
- Minfang Li
- Department of Respiratory Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
- The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China
| | - Dan Jia
- Department of Respiratory Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
- The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China
| | - Jinshuai Li
- Department of Respiratory Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
| | - Yaqing Li
- Department of Respiratory Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
| | - Yaqiong Wang
- Department of Respiratory Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, 518033, China
| | - Yuting Wang
- Department of Respiratory Medicine, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, 215300, China.
| | - Wei Xie
- Department of Respiratory Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China.
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.
| | - Sheng Chen
- Department of Respiratory Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, China.
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.
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Feng Y, Guo K, Jiang J, Lin S. Mesenchymal stem cell-derived exosomes as delivery vehicles for non-coding RNAs in lung diseases. Biomed Pharmacother 2024; 170:116008. [PMID: 38071800 DOI: 10.1016/j.biopha.2023.116008] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 12/02/2023] [Accepted: 12/06/2023] [Indexed: 01/10/2024] Open
Abstract
The burden of lung diseases is gradually increasing with an increase in the average human life expectancy. Therefore, it is necessary to identify effective methods to treat lung diseases and reduce their social burden. Currently, an increasing number of studies focus on the role of mesenchymal stem cell-derived exosomes (MSC-Exos) as a cell-free therapy in lung diseases. They show great potential for application to lung diseases as a more stable and safer option than traditional cell therapies. MSC-Exos are rich in various substances, including proteins, nucleic acids, and DNA. Delivery of Non-coding RNAs (ncRNAs) enables MSC-Exos to communicate with target cells. MSC-Exos significantly inhibit inflammatory factors, reduce oxidative stress, promote normal lung cell proliferation, and reduce apoptosis by delivering ncRNAs. Moreover, MSC-Exos carrying specific ncRNAs affect the proliferation, invasion, and migration of lung cancer cells, thereby playing a role in managing lung cancer. The detailed mechanisms of MSC-Exos in the clinical treatment of lung disease were explored by developing standardized culture, isolation, purification, and administration strategies. In summary, MSC-Exo-based delivery methods have important application prospects for treating lung diseases.
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Affiliation(s)
- Yuqian Feng
- Hangzhou School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China
| | - Kaibo Guo
- Department of Oncology, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310003, China
| | - Jing Jiang
- The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China
| | - Shengyou Lin
- Department of Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang 310006, China.
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15
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Zhai Z, Cui T, Chen J, Mao X, Zhang T. Advancements in engineered mesenchymal stem cell exosomes for chronic lung disease treatment. J Transl Med 2023; 21:895. [PMID: 38071321 PMCID: PMC10709966 DOI: 10.1186/s12967-023-04729-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 11/13/2023] [Indexed: 12/18/2023] Open
Abstract
Chronic lung diseases include an array of conditions that impact airways and lung structures, leading to considerable societal burdens. Mesenchymal stem cells (MSCs) and their exosomes (MSC-exos) can be used for cell therapy and exhibit a diverse spectrum of anti-inflammatory, antifibrotic, and immunomodulatory properties. Engineered MSC-exos possesses enhanced capabilities for targeted drug delivery, resulting in more potent targeting effects. Through various engineering modifications, these exosomes can exert many biological effects, resulting in specific therapeutic outcomes for many diseases. Moreover, engineered stem cell exosomes may exhibit an increased capacity to traverse physiological barriers and infiltrate protected lesions, thereby exerting their therapeutic effects. These characteristics render them a promising therapeutic agent for chronic pulmonary diseases. This article discusses and reviews the strategies and mechanisms of engineered MSC-exos in the treatment of chronic respiratory diseases based on many studies to provide new solutions for these diseases.
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Affiliation(s)
- Zhengyao Zhai
- The First School of Medicine, School of Information and Engineering, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China
| | - Tairong Cui
- The First School of Medicine, School of Information and Engineering, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China
| | - Jialiang Chen
- The First School of Medicine, School of Information and Engineering, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China
| | - Xulong Mao
- Key Laboratory of Heart and Lung, Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
| | - Ting Zhang
- Department of Rheumatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
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16
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Zang H, Wang Z, Wu Q, Shi L, Chen G. Effect of hypoxia on the expression of microRNA in extracellular vesicles of human umbilical cord stem cells in vitro. Cell Tissue Bank 2023; 24:769-778. [PMID: 37221283 DOI: 10.1007/s10561-023-10095-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 04/24/2023] [Indexed: 05/25/2023]
Abstract
Mesenchymal stem cells (MSCs) derived extracellular vesicles, which have been shown to possess therapeutic effects for many diseases. However, how hypoxic conditions would affect exosomal microRNA expression in human umbilical cord MSCs (hUC-MSCs) is currently not investigated. This study aims to investigate the potential function of in vitro microRNAs of hUC-MSC cultured under normoxic and hypoxic conditions. Extracellular vesicles secreted from hUC-MSCs cultured in normoxic (21% O2) and hypoxic (5% O2) conditions were collected for microRNA identification. Zeta View Laser Scattering and transmission electron microscopy were used to observe the size and morphology of extracellular vesicles. qRT-PCR was performed to measure the expression of related microRNAs. The Gene Ontology and KEGG pathway were used to predict the function of microRNAs. Finally, the effects of hypoxia on the expression of related mRNAs and cellular activity were examined. This study identified 35 upregulated and 8 downregulated microRNAs in the hypoxia group. We performed target genes analysis to explore the potential function of these microRNA upregulated in the hypoxia group. Significant enrichment of the cell proliferation, pluripotency of stem cells, MAPK, Wnt, and adherens junction pathways were observed in the GO and KEGG pathways. Under hypoxic conditions, the expression levels of 7 target genes were lower than that of the normal environment. In conclusion, this study demonstrated for the first time that microRNA expression in extracellular vesicles of human umbilical vein stem cells cultured under hypoxia is different from that under normal conditions, and these microRNAs may be markers for detecting hypoxia.
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Affiliation(s)
- Huifen Zang
- Department of Obstetrics, The NO. 8 People's Hospital of Qingdao, Qingdao, 266100, China.
| | - Zhaohui Wang
- Department of Obstetrics, The NO. 8 People's Hospital of Qingdao, Qingdao, 266100, China
| | - Qingqing Wu
- Department of Obstetrics, The NO. 8 People's Hospital of Qingdao, Qingdao, 266100, China
| | - Lei Shi
- Department of Obstetrics, The NO. 8 People's Hospital of Qingdao, Qingdao, 266100, China
| | - Ge Chen
- Department of Obstetrics, The NO. 8 People's Hospital of Qingdao, Qingdao, 266100, China
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Xiao B, Li L, Yao D, Mo B. Noncoding RNAs in asthmatic airway smooth muscle cells. Eur Respir Rev 2023; 32:32/168/220184. [PMID: 37076176 PMCID: PMC10113956 DOI: 10.1183/16000617.0184-2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 02/07/2023] [Indexed: 04/21/2023] Open
Abstract
Asthma is a complex and heterogeneous airway disease caused by genetic, environmental and epigenetic factors treated with hormones and biologics. Irreversible pathological changes to airway smooth muscle cells (ASMCs) such as hyperplasia and hypertrophy can occur in asthmatic patients. Determining the mechanisms responsible is vital for preventing such changes. In recent years, noncoding RNAs (ncRNAs), especially microRNAs, long noncoding RNAs and circular RNAs, have been found to be associated with abnormalities of the ASMCs. This review highlights recent ncRNA research into ASMC pathologies. We present a schematic that illustrates the role of ncRNAs in pathophysiological changes to ASMCs that may be useful in future research in diagnostic and treatment strategies for patients with asthma.
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Affiliation(s)
- Bo Xiao
- Laboratory of Respiratory Disease, Affiliated Hospital of Guilin Medical University, Guilin, China
- Key Laboratory of Respiratory Diseases, Education Department of Guangxi Zhuang Autonomous Region, Guilin, China
- These authors contributed equally to this work
| | - Liangxian Li
- Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin, China
- These authors contributed equally to this work
| | - Dong Yao
- Key Laboratory of Respiratory Diseases, Education Department of Guangxi Zhuang Autonomous Region, Guilin, China
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
- These authors contributed equally to this work
| | - Biwen Mo
- Key Laboratory of Respiratory Diseases, Education Department of Guangxi Zhuang Autonomous Region, Guilin, China
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
- Key Laboratory of Glucose and Lipid Metabolism Disorders, Guangxi Health Commission, Guilin, China
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Zhao K, Kong C, Shi N, Jiang J, Li P. Potential angiogenic, immunomodulatory, and antifibrotic effects of mesenchymal stem cell-derived extracellular vesicles in systemic sclerosis. Front Immunol 2023; 14:1125257. [PMID: 37251412 PMCID: PMC10213547 DOI: 10.3389/fimmu.2023.1125257] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 04/24/2023] [Indexed: 05/31/2023] Open
Abstract
Systemic sclerosis (SSc) is an intricate systemic autoimmune disease with pathological features such as vascular injury, immune dysregulation, and extensive fibrosis of the skin and multiple organs. Treatment options are limited; however, recently, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been acknowledged in preclinical and clinical trials as being useful in treating autoimmune diseases and are likely superior to MSCs alone. Recent research has also shown that MSC-EVs can ameliorate SSc and the pathological changes in vasculopathy, immune dysfunction, and fibrosis. This review summarizes the therapeutic effects of MSC-EVs on SSc and the mechanisms that have been discovered to provide a theoretical basis for future studies on the role of MSC-EVs in treating SSc.
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Affiliation(s)
- Kelin Zhao
- Department of Rheumatology and Immunology, China-Japan Union Hospital, Jilin University, Changchun, China
| | - Chenfei Kong
- Scientific Research Center, China-Japan Union Hospital, Jilin University, Changchun, China
| | - Naixu Shi
- Department of Stomatology, China-Japan Union Hospital, Jilin University, Changchun, China
| | - Jinlan Jiang
- Scientific Research Center, China-Japan Union Hospital, Jilin University, Changchun, China
| | - Ping Li
- Department of Rheumatology and Immunology, China-Japan Union Hospital, Jilin University, Changchun, China
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Bhat S, Rotti H, Prasad K, Kabekkodu SP, Saadi AV, Shenoy SP, Joshi KS, Nesari TM, Shengule SA, Dedge AP, Gadgil MS, Dhumal VR, Salvi S, Satyamoorthy K. Genome-wide DNA methylation profiling after Ayurveda intervention to bronchial asthmatics identifies differential methylation in several transcription factors with immune process related function. J Ayurveda Integr Med 2023; 14:100692. [PMID: 37018893 PMCID: PMC10122039 DOI: 10.1016/j.jaim.2023.100692] [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: 12/15/2021] [Revised: 10/13/2022] [Accepted: 02/01/2023] [Indexed: 04/05/2023] Open
Abstract
BACKGROUND The Indian traditional medicinal system, Ayurveda, describes several lifestyle practices, processes and medicines as an intervention to treat asthma. Rasayana therapy is one of them and although these treatment modules show improvement in bronchial asthma, their mechanism of action, particularly the effect on DNA methylation, is largely understudied. OBJECTIVES Our study aimed at identifying the contribution of DNA methylation changes in modulating bronchial asthma phenotype upon Ayurveda intervention. MATERIALS AND METHODS In this study, genome-wide methylation profiling in peripheral blood DNA of healthy controls and bronchial asthmatics before (BT) and after (AT) Ayurveda treatment was performed using array-based profiling of reference-independent methylation status (aPRIMES) coupled to microarray technique. RESULTS We identified 4820 treatment-associated DNA methylation signatures (TADS) and 11,643 asthma-associated DNA methylation signatures (AADS), differentially methylated [FDR (≤0.1) adjusted p-values] in AT and HC groups respectively, compared to BT group. Neurotrophin TRK receptor signaling pathway was significantly enriched for differentially methylated genes in bronchial asthmatics, compared to AT and HC subjects. Additionally, we identified over 100 differentially methylated immune-related genes located in the promoter/5'-UTR regions of TADS and AADS. Various immediate-early response and immune regulatory genes with functions such as transcription factor activity (FOXD1, FOXD2, GATA6, HOXA3, HOXA5, MZF1, NFATC1, NKX2-2, NKX2-3, RUNX1, KLF11), G-protein coupled receptor activity (CXCR4, PTGER4), G-protein coupled receptor binding (UCN), DNA binding (JARID2, EBF2, SOX9), SNARE binding (CAPN10), transmembrane signaling receptor activity (GP1BB), integrin binding (ITGA6), calcium ion binding (PCDHGA12), actin binding (TRPM7, PANX1, TPM1), receptor tyrosine kinase binding (PIK3R2), receptor activity (GDNF), histone methyltransferase activity (MLL5), and catalytic activity (TSTA3) were found to show consistent methylation status between AT and HC group in microarray data. CONCLUSIONS Our study reports the DNA methylation-regulated genes in bronchial asthmatics showing improvement in symptoms after Ayurveda intervention. DNA methylation regulation in the identified genes and pathways represents the Ayurveda intervention responsive genes and may be further explored as diagnostic, prognostic, and therapeutic biomarkers for bronchial asthma in peripheral blood.
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Affiliation(s)
- Smitha Bhat
- Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Harish Rotti
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Keshava Prasad
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Shama Prasada Kabekkodu
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Abdul Vahab Saadi
- Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Sushma P Shenoy
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Kalpana S Joshi
- Department of Biotechnology, Sinhgad College of Engineering, S. P. University of Pune, Pune Maharashtra, India
| | - Tanuja M Nesari
- Department of Dravyaguna, Tilak Ayurved Mahavidyalaya, Pune, Maharashtra, India
| | - Sushant A Shengule
- Department of Biotechnology, Sinhgad College of Engineering, S. P. University of Pune, Pune Maharashtra, India
| | - Amrish P Dedge
- Department of Dravyaguna, Tilak Ayurved Mahavidyalaya, Pune, Maharashtra, India
| | - Maithili S Gadgil
- Department of Biotechnology, Sinhgad College of Engineering, S. P. University of Pune, Pune Maharashtra, India
| | - Vikram R Dhumal
- Department of Dravyaguna, Tilak Ayurved Mahavidyalaya, Pune, Maharashtra, India
| | - Sundeep Salvi
- Department of Pulmonary Medicine, Chest Research Foundation, Pune, Maharashtra, India
| | - Kapaettu Satyamoorthy
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India.
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20
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Cai Y, Tian J, Su Y, Shi X. MiR-506 targets polypyrimidine tract-binding protein 1 to inhibit airway inflammatory response and remodeling via mediating Wnt/β-catenin signaling pathway. Allergol Immunopathol (Madr) 2023; 51:15-24. [PMID: 37169555 DOI: 10.15586/aei.v51i3.676] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 10/12/2022] [Indexed: 05/13/2023]
Abstract
BACKGROUND Airway remodeling, which contributes to the clinical course of childhood asthma, occurs due to airway inflammation and is featured by anomalous biological behaviors of airway smooth muscle cells (ASMCs). microRNA (miRNA) plays an essential role in the etiopathogenesis of asthma. OBJECTIVE This research was aimed to characterize miR-506 in asthma and uncover potential regulatory machinery. MATERIAL AND METHODS The asthmatic cell model was established by treating ASMCs with transforming growth factor-beta1 (TGF-β1) and assessed by the levels of interleukin (IL)-1β and interferon gamma (IFN-γ). Using real-time quantitative polymerase chain reaction, mRNA expression of miR-506 and polypyrimidine tract-binding protein 1 (PTBP1) was measured. Cell counting kit-8 and Transwell migration tests were used for estimating the capacity of ASMCs to proliferate and migrate. Luciferase reporter assay was used to corroborate whether miR-506 was directly bound to PTBP1. Expression of PTBP1, collagen I and III, and essential proteins of the wingless-related integration (Wnt)/β-catenin pathway (β-catenin, c-MYC and cyclin D1) was accomplished by Western blot analysis. The involvement of Wnt/β-catenin signaling in asthma was confirmed by Wnt signaling pathway inhibitor (IWR-1). RESULTS miR-506 was poorly expressed in asthmatic tissues and cell model. Functionally, overexpression of miR-506 reduced aberrant proliferation, migration, inflammation and collagen deposition of ASMCs triggered by TGF-β1. Mechanically, miR-506 directly targeted the 3' untranslated region (3-UTR) of PTBP1 and had a negative regulation on PTBP1 expression. Moreover, overexpression of miR-506 suppressed the induction of Wnt/β-catenin pathway. The administration of IWR-1 further validated negative correlation between miR-506 and the Wnt/β-catenin pathway in asthma. CONCLUSION Our data indicated that targeting miR-506/PTBP1/Wnt/β-catenin axis might point in a helpful direction for treating asthma in children.
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Affiliation(s)
- Yuxiang Cai
- Department of Emergency, Xi'an Children's Hospital, Xi'an, Shaanxi, China
| | - Jifeng Tian
- Department of Integrated Traditional Chinese and Western Medicine, Xi'an Children's Hospital, Xi'an, Shaanxi, China
| | - Yufei Su
- Department of Emergency, Xi'an Children's Hospital, Xi'an, Shaanxi, China
| | - Xiaolan Shi
- Department of Respiratory Asthma Center, Xi'an Children's Hospital, Xi'an, Shaanxi, China;
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Huang S, Li Y, Zeng J, Chang N, Cheng Y, Zhen X, Zhong D, Chen R, Ma G, Wang Y. Mesenchymal Stem/Stromal Cells in Asthma Therapy: Mechanisms and Strategies for Enhancement. Cell Transplant 2023; 32:9636897231180128. [PMID: 37318186 DOI: 10.1177/09636897231180128] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023] Open
Abstract
Asthma is a complex and heterogeneous disease characterized by chronic airway inflammation, airway hyperresponsiveness, and airway remodeling. Most asthmatic patients are well-established using standard treatment strategies and advanced biologicals. However, a small group of patients who do not respond to biological treatments or are not effectively controlled by available treatment strategies remain a clinical challenge. Therefore, new therapies are urgently needed for poorly controlled asthma. Mesenchymal stem/stromal cells (MSCs) have shown therapeutic potential in relieving airway inflammation and repairing impaired immune balance in preclinical trials owing to their immunomodulatory abilities. Noteworthy, MSCs exerted a therapeutic effect on steroid-resistant asthma with rare side effects in asthmatic models. Nevertheless, adverse factors such as limited obtained number, nutrient and oxygen deprivation in vitro, and cell senescence or apoptosis affected the survival rate and homing efficiency of MSCs, thus limiting the efficacy of MSCs in asthma. In this review, we elaborate on the roles and underlying mechanisms of MSCs in the treatment of asthma from the perspective of their source, immunogenicity, homing, differentiation, and immunomodulatory capacity and summarize strategies to improve their therapeutic effect.
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Affiliation(s)
- Si Huang
- Department of Pediatrics, Shunde Women and Children's Hospital of Guangdong Medical University, Foshan, China
- Institute of Respiratory Diseases, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan, China
| | - Yiyang Li
- Department of Pediatrics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Jieqing Zeng
- Department of Pediatrics, Shunde Women and Children's Hospital of Guangdong Medical University, Foshan, China
- Institute of Respiratory Diseases, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan, China
| | - Ning Chang
- Department of Pediatrics, Shunde Women and Children's Hospital of Guangdong Medical University, Foshan, China
- Institute of Respiratory Diseases, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan, China
| | - Yisen Cheng
- Department of Pediatrics, Shunde Women and Children's Hospital of Guangdong Medical University, Foshan, China
- Institute of Respiratory Diseases, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan, China
| | - Xiangfan Zhen
- Department of Pediatrics, Shunde Women and Children's Hospital of Guangdong Medical University, Foshan, China
- Institute of Respiratory Diseases, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan, China
| | - Dan Zhong
- Department of Pediatrics, Shunde Women and Children's Hospital of Guangdong Medical University, Foshan, China
- Institute of Respiratory Diseases, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan, China
| | - Riling Chen
- Department of Pediatrics, Shunde Women and Children's Hospital of Guangdong Medical University, Foshan, China
- Institute of Respiratory Diseases, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan, China
| | - Guoda Ma
- Department of Pediatrics, Shunde Women and Children's Hospital of Guangdong Medical University, Foshan, China
- Institute of Respiratory Diseases, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan, China
| | - Yajun Wang
- Department of Pediatrics, Shunde Women and Children's Hospital of Guangdong Medical University, Foshan, China
- Institute of Respiratory Diseases, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan, China
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22
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Ambrożej D, Stelmaszczyk-Emmel A, Czystowska-Kuźmicz M, Feleszko W. "Liquid biopsy" - extracellular vesicles as potential novel players towards precision medicine in asthma. Front Immunol 2022; 13:1025348. [PMID: 36466836 PMCID: PMC9714548 DOI: 10.3389/fimmu.2022.1025348] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 10/31/2022] [Indexed: 12/02/2023] Open
Abstract
Extracellular vesicles (EVs) have emerged as vital mediators in intracellular communication in the lung microenvironment. Environmental exposure to various triggers (e.g., viruses, allergens) stimulates the EV-mediated cascade of pro-inflammatory responses that play a key role in the asthma pathomechanism. This complex EV-mediated crosstalk in the asthmatic lung microenvironment occurs between different cell types, including airway epithelial cells and immune cells. The cargo composition of EVs mirrors hereby the type and activation status of the parent cell. Therefore, EVs collected in a noninvasive way (e.g., in nasal lavage, serum) could inform on the disease status as a "liquid biopsy", which is particularly important in the pediatric population. As a heterogeneous disease, asthma with its distinct endotypes and phenotypes requires more investigation to develop novel diagnostics and personalized case management. Filling these knowledge gaps may be facilitated by further EV research. Here, we summarize the contribution of EVs in the lung microenvironment as potential novel players towards precision medicine in the development of asthma. Although rapidly evolving, the EV field is still in its infancy. However, it is expected that a better understanding of the role of EVs in the asthma pathomechanism will open up new horizons for precision medicine diagnostic and therapeutic solutions.
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Affiliation(s)
- Dominika Ambrożej
- Department of Pediatric Pneumonology and Allergy, Medical University of Warsaw, Warsaw, Poland
- Doctoral School, Medical University of Warsaw, Warsaw, Poland
| | - Anna Stelmaszczyk-Emmel
- Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Medical University of Warsaw, Warsaw, Poland
| | | | - Wojciech Feleszko
- Department of Pediatric Pneumonology and Allergy, Medical University of Warsaw, Warsaw, Poland
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23
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Zhang Y, Huo M, Wang Y, Xiao L, Wu J, Ma Y, Zhang D, Lang X, Wang X. A tailored bioactive 3D porous poly(lactic-acid)-exosome scaffold with osteo-immunomodulatory and osteogenic differentiation properties. J Biol Eng 2022; 16:22. [PMID: 35996115 PMCID: PMC9394013 DOI: 10.1186/s13036-022-00301-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 08/08/2022] [Indexed: 11/10/2022] Open
Abstract
Polylactic acid (PLA) is a versatile and biodegradable scaffold widely used in biomedical fields to repair tissue defects. Exosomes derived from mesenchymal stem cells (MSCs) are nano-sized extracellular vesicles, which play an important role in tissue engineering in recent years. The primary focus of this study was to develop a bioactive 3D PLA scaffold using exosome-based strategy to improve its osteogenic and immunoregulatory potential. We firstly successfully isolated MSC-derived exosomes (MSC-Exo). Morphological analysis revealed that MSC-Exo exhibits a typical cup-shaped morphology with high expression of exosomal marker CD63. MSC-Exo internalization into recipient cells were also investigated using flow cytometry and confocal laser scanning microscopy. Porous 3D PLA scaffold coated MSC-Exo were used for immunoregulatory and osteogenic testing. Exosomes released from 3D PLA scaffold were validated in RAW264.7 and hBMSCs. The cell proliferation and live/dead assay indicated high biocompatibility for PLA-Exo scaffold. Additionally, PLA-Exo scaffold could reduce the pro-inflammatory marker expression and reactive oxygen species (ROS) production, indicating potential immunoregulatory potential. It is also confirmed that PLA-Exo scaffold could potentiate osteogenic differentiation in the osteogenesis assay. In conclusion, our results demonstrate this bioactive 3D-printed PLA scaffolds with MSC-Exo modification holds immunoregulatory potential and favor osteogenic differentiation, thus having potential applications in bone tissue regeneration.
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Affiliation(s)
- Yi Zhang
- Department of Hygiene Toxicology, Zunyi Medical University, Zunyi, 563000, Guizhou, China
| | - Mengjie Huo
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China
| | - Yi Wang
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China
| | - Lan Xiao
- School of Mechanical, Medical & Process Engineering, Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD, 4000, Australia.,Australia China Centre for Tissue Engineering and Regenerative Medicine, Kelvin Grove, Brisbane, Queensland, 4059, Australia
| | - Jianmei Wu
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China
| | - Yaping Ma
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China
| | - Dingmei Zhang
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China
| | - Xuemei Lang
- Department of Pre-hospital Emergency, Central Hospital of Chongqing University / Chongqing Emergency Medical Center, Chongqing, Chongqing, 400014, China.
| | - Xin Wang
- Department of Hygiene Toxicology, Zunyi Medical University, Zunyi, 563000, Guizhou, China. .,Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China. .,School of Mechanical, Medical & Process Engineering, Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD, 4000, Australia. .,Australia China Centre for Tissue Engineering and Regenerative Medicine, Kelvin Grove, Brisbane, Queensland, 4059, Australia.
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24
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Lee S, Ko JH, Kim SN. The Extracellular MicroRNAs on Inflammation: A Literature Review of Rodent Studies. Biomedicines 2022; 10:1601. [PMID: 35884901 PMCID: PMC9312877 DOI: 10.3390/biomedicines10071601] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 07/03/2022] [Accepted: 07/03/2022] [Indexed: 11/17/2022] Open
Abstract
Inflammation is an indispensable biological process stimulated by infection and injuries. Inflammatory mechanisms related to extracellular vesicles (EVs), which are small membrane structures carrying various molecules, were summarized in this review. Emerging evidence from animal studies has highlighted the role of EVs in modulating inflammatory responses, by transporting various molecules involved in host defense. In this review, we have discussed the role of EV miRNAs in inflammation. Rodent studies associated with extracellular miRNAs in inflammatory diseases, published from 2012 to 2022, were explored from PUBMED, EMBASE, and MEDLINE. A total of 95 studies were reviewed. In summary, EV-associated miRNAs play a key role in various diseases, including organ injury, immune dysfunction, neurological disease, metabolic syndrome, vesicular disease, arthritis, cancer, and other inflammatory diseases. Diverse EV-associated miRNAs regulate inflammasome activation and pro- and anti-inflammatory cytokine levels by targeting genes.
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Affiliation(s)
- Seri Lee
- College of Korean Medicine, Dongguk University, Goyang 10326, Korea; (S.L.); (J.H.K.)
- Graduate School, Dongguk University, Seoul 04620, Korea
| | - Jade Heejae Ko
- College of Korean Medicine, Dongguk University, Goyang 10326, Korea; (S.L.); (J.H.K.)
| | - Seung-Nam Kim
- College of Korean Medicine, Dongguk University, Goyang 10326, Korea; (S.L.); (J.H.K.)
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25
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Abbaszadeh H, Ghorbani F, Abbaspour-Aghdam S, Kamrani A, Valizadeh H, Nadiri M, Sadeghi A, Shamsasenjan K, Jadidi-Niaragh F, Roshangar L, Ahmadi M. Chronic obstructive pulmonary disease and asthma: mesenchymal stem cells and their extracellular vesicles as potential therapeutic tools. Stem Cell Res Ther 2022; 13:262. [PMID: 35725505 PMCID: PMC9208161 DOI: 10.1186/s13287-022-02938-5] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 05/31/2022] [Indexed: 12/15/2022] Open
Abstract
Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and asthma, are one of the most frequent causes of morbidity and mortality in the global. COPD is characterized by progressive loss of lung function through inflammation, apoptosis, and oxidative stress caused by chronic exposure to harmful environmental pollutants. Airway inflammation and epithelial remodeling are also two main characteristics of asthma. In spite of extensive efforts from researchers, there is still a great need for novel therapeutic approaches for treatment of these conditions. Accumulating evidence suggests the potential role of mesenchymal stem cells (MSCs) in treatment of many lung injuries due to their beneficial features including immunomodulation and tissue regeneration. Besides, the therapeutic advantages of MSCs are chiefly related to their paracrine functions such as releasing extracellular vesicles (EVs). EVs comprising exosomes and microvesicles are heterogeneous bilayer membrane structures loaded with various lipids, nucleic acids and proteins. Due to their lower immunogenicity, tumorigenicity, and easier management, EVs have appeared as favorable alternatives to stem cell therapies. Therefore, in this review, we provided an overview on the current understanding of the importance of MSCs and MSC-derived EVs from different sources reported in preclinical and clinical COPD and asthmatic models.
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Affiliation(s)
- Hossein Abbaszadeh
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Farzaneh Ghorbani
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Amin Kamrani
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hamed Valizadeh
- Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Nadiri
- Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran
| | - Armin Sadeghi
- Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran
| | - Karim Shamsasenjan
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Leila Roshangar
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Majid Ahmadi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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