Article
Engineering, Biomedical
Raphael J. Crum, Hector Capella-Monsonis, Jordan Chang, Marley J. Dewey, Brian D. Kolich, Kelsey T. Hall, Salma O. El-Mossier, David G. Nascari, George S. Hussey, Stephen F. Badylak
Summary: Matrix-bound nanovesicles (MBV) are a distinct subtype of bioactive extracellular vesicles that are embedded within the extracellular matrix (ECM). Recent studies have demonstrated the therapeutic potential of MBV in models of retinal damage and rheumatoid arthritis by targeting immunomodulation. However, the biocompatibility and biodistribution of MBV in vitro and in vivo have not been fully characterized. This study comprehensively examined the pre-clinical safety profile of MBV and found that they are well-tolerated, non-toxic, and non-immunosuppressive. These findings highlight the translational feasibility of MBV therapeutics for various clinical applications.
ACTA BIOMATERIALIA
(2023)
Article
Cell Biology
Alex Hildebrandt, Benedikt Kirchner, Agnes S. Meidert, Florian Brandes, Anja Lindemann, Gero Doose, Alexander Doege, Rolf Weidenhagen, Marlene Reithmair, Gustav Schelling, Michael W. Pfaffl
Summary: The study analyzed serum-derived miRNA profiles from patients and volunteers to identify potential biomarkers for atherosclerosis. The differential expression analysis found 27 differentially expressed miRNAs in patients compared to healthy volunteers, with specific miRNA fingerprints for different atherosclerotic manifestations. Overrepresentation analysis revealed relevant biological processes related to atherosclerosis, indicating the potential of these miRNAs as biomarker candidates.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Maria Isabel Gonzalez, Mario Gonzalez-Arjona, Ana Santos-Coquillat, Javier Vaquero, Elena Vazquez-Ogando, Antonio de Molina, Hector Peinado, Manuel Desco, Beatriz Salinas
Summary: A novel chemical approach for robust attachment of commercial fluorescent dyes to exosome surface was reported, demonstrating no alteration of original physicochemical properties. Successful validation of the methodology in cell cultures and healthy mice indicates its potential for in vitro and in vivo applications. The fluorescently labeled exosomes were effectively visualized with optical imaging.
Article
Cell & Tissue Engineering
Pengyu Hong, Xiaoyang Xu, Xin Hu, Hao Yang, Yue Wu, Juan Chen, Kun Li, Zhangui Tang
Summary: The study demonstrated that sEV-LT promoted adipose tissue regeneration by accelerating proliferation, migration, and adipogenic differentiation of ADSCs in vitro and recruiting adipocytes and promoting angiogenesis in vivo. sEV-LT could serve as an alternative cell-free therapeutic strategy for generating adipose tissue, showing promising application prospects in tissue engineering.
STEM CELL RESEARCH & THERAPY
(2021)
Review
Biotechnology & Applied Microbiology
Nastaran Hadizadeh, Diba Bagheri, Mehdi Shamsara, Michael R. Hamblin, Abbas Farmany, Mengdi Xu, Zhuobin Liang, Farideh Razi, Ehsan Hashemi
Summary: The rise of exosomes as carriers of natural biomarkers has attracted attention in the field of early disease diagnosis. This review discusses exosome biogenesis, their role as biomarkers in metabolic disorders, recent advances in exosome detection and isolation technologies, as well as future research directions and challenges in manipulating and genetically engineering exosomes for disease diagnosis.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Immunology
Zhaochen Zhu, Renzhi Gao, Teng Ye, Kai Feng, Juntao Zhang, Yu Chen, Zongping Xie, Yang Wang
Summary: The study demonstrated that local injection of iMSC-sEVs effectively reduced pain in rat tendinopathy model, ameliorated tendon histology, promoted tenocyte proliferation, and decreased expression of proinflammatory cytokines. Transcriptome analysis revealed that iMSC-sEVs treatment upregulated genes related to cell proliferation and downregulated genes involved in inflammation and collagen degeneration. These findings suggest that iMSC-sEVs could be a promising therapeutic candidate for tendinopathy.
JOURNAL OF INFLAMMATION RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Yanxia Chen, Yinghong Shi, Zhimin Tao
Summary: This study used organic and inorganic dyes to stain small extracellular vesicles (sEVs) derived from different cell lines, and tracked their fluorescence signals in a gastric cancer xenograft murine model. The study compared the behavior of different dye-stained sEVs in terms of circulation, biodistribution, and tumor accumulation. The results showed that different fluorescent dyes led to distinct tumor accumulation patterns, while sEVs from different cell lines exhibited similar circulation and tumor accumulation behavior. This study suggests that single staining of sEVs membrane should be avoided when examining the biological fate of sEVs.
Article
Chemistry, Multidisciplinary
Bryan John Abel Magoling, Anthony Yan-Tang Wu, Yen-Ju Chen, Wendy Wan-Ting Wong, Steven Ting-Yu Chuo, Hsi-Chien Huang, Yun-Chieh Sung, Hsin Tzu Hsieh, Poya Huang, Kang-Zhang Lee, Kuan-Wei Huang, Ruey-Hwa Chen, Yunching Chen, Charles Pin-Kuang Lai
Summary: Extracellular vesicles (EVs), including small EVs (sEVs, exosomes) and medium to large EVs (bEVs, microvesicles), play important roles in intercellular communication in breast cancer. This study identifies distinct properties and functions of bEVs and sEVs in breast cancer, showing that bEVs are released in a higher ratio in aggressive triple-negative breast cancer subtype. Both bEVs and sEVs promote tumor growth in a murine model, and they share common tumor-progression-associated EV surface membrane proteins. Depletion of these proteins reduces the protumorigenic potential of EVs. This study highlights the significance of bEVs in breast cancer and suggests their potential diagnostic and therapeutic applications.
ADVANCED MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Sandra Tejedor, Marc Buigues, Hernan Gonzalez-King, Andreia M. Silva, Nahuel Aquiles Garcia, Niek Dekker, Pilar Sepulveda
Summary: Myocardial fibrosis, a pathological feature of cardiac dysfunction, can be suppressed by OSM released by macrophages during cardiac fibrosis. In this study, we developed MSC-T cell lines engineered to display cleavage-resistant OSM fused to CD81TM on the surface of SEVs. The OSM-loaded SEVs showed decreased proliferation and reduced telo-collagen expression in activated HCF-Vs, and also reduced fibrosis, prevented cardiac hypertrophy, and increased angiogenesis when injected into mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Ana Mencher, Miguel Mejias-Ortiz, Pilar Morales, Jordi Tronchoni, Ramon Gonzalez
Summary: Malolactic fermentation is crucial for the quality of red wines. This study reports the production and characterization of extracellular vesicles by Oenococcus oeni, a common bacteria involved in spontaneous malolactic fermentation. The findings contribute to the understanding of microbial interactions during wine fermentation.
Article
Chemistry, Analytical
Xiaohui Chen, Yun Deng, Ruyan Niu, Zixin Sun, Alya Batool, Liu Wang, Chong Zhang, Ningyu Ma, Qingtang Yang, Guoxiang Liu, Jichun Yang, Yang Luo
Summary: In this study, a Programmable Isothermal Cascade Keen Enzyme-free Reporter (PICKER) was constructed for the accurate detection of cancer-derived small extracellular vesicles (csEVs). A novel particle ratio index (PRcsEV/tsEV) was proposed as a potential indicator of breast cancer staging.
ANALYTICAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Abir Salek, Mouna Selmi, Mahassen Barboura, M. Carmen Martinez, Leila Chekir-Ghedira, Ramaroson Andriantsitohaina
Summary: This study utilized small extracellular vesicles (sEVs) to enhance the stability and efficacy of berberine hydrochloride (BRB). The results showed that sEVs loaded with BRB had greater inhibitory effects on proliferation, migration, and capillary-like formation in tumor cells and endothelial cells compared to free BRB. Therefore, sEV-loaded BRB may be considered as an innovative delivery method to prevent tumorigenesis and angiogenesis.
Article
Chemistry, Multidisciplinary
Xin Min, Xiao-Hui Deng, Huilin Lao, Zi-Cong Wu, Yi Chen, Yuelian Luo, Haoyang Wu, Junbo Wang, Qing-Ling Fu, Hao Xiong
Summary: In this study, mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) were used as nanoscale vehicles to deliver brain-derived neurotrophic factor (BDNF) for the treatment of noise-induced hearing loss (NIHL). The results showed that BDNF-loaded sEVs efficiently increased the expression of BDNF protein in the cochlea, and significantly attenuated cochlear hair cell loss and NIHL in mice. Transcriptomic analysis also revealed the involvement of various mRNAs and miRNAs in the protective actions of BDNF-sEVs against oxidative stress.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Biochemistry & Molecular Biology
Shuhiba Mohammad, Jayonta Bhattacharjee, Velislava Tzaneva, Kelly Ann Hutchinson, Madeeha Shaikh, Danilo Fernandes da Silva, Dylan Burger, Kristi. B. B. Adamo
Summary: Exercise induces the release of small extracellular vesicles (sEVs) that may play a role in tissue cross-talk during exercise. In this study, sEVs released after exercise in pregnant and non-pregnant individuals were evaluated for their impact on trophoblasts in vitro. The results showed that exercise-associated sEVs localized within the cytoplasm of trophoblast cells, but did not significantly affect cell proliferation, gene expression, or hormone release. Further investigation is needed to reveal the potential role of exercise-associated sEVs in communicating the effects of exercise to the maternal-fetal interface.
Article
Chemistry, Multidisciplinary
Feng Xie, Peng Su, Ting Pan, Xiaoxue Zhou, Heyu Li, Huizhe Huang, Aijun Wang, Fangwei Wang, Jun Huang, Haiyan Yan, Linghui Zeng, Long Zhang, Fangfang Zhou
Summary: ACE2 plays a key role in the interaction with SARS-CoV-2, and its levels in extracellular vesicles are regulated by protein palmitoylation. Modifying ACE2 with palmitoylation affects its membrane-targeting and secretion in EVs, showing potential for neutralizing SARS-CoV-2.
ADVANCED MATERIALS
(2021)
Article
Nanoscience & Nanotechnology
Lais Ribovski, Edwin de Jong, Olga Mergel, Guangyue Zu, Damla Keskin, Patrick van Rijn, Inge S. Zuhorn
Summary: This study investigated the effect of nanoparticle stiffness on transport across the blood-brain barrier, finding that more densely cross-linked nanogels showed higher uptake by brain endothelial cells, while less densely cross-linked nanogels demonstrated higher transcytotic potential. These findings suggest that nanogel stiffness has opposing effects on nanogel uptake and transcytosis at the BBB.
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Gabriel Vasata Furtado, Jing Yang, Di Wu, Christos Papagiannopoulos, Hanna M. Terpstra, E. F. Elsiena Kuiper, Sybille Krauss, Wei-Guo Zhu, Harm H. Kampinga, Steven Bergink
Summary: FOXO1 prevents toxic polyQ aggregation and reduces the synthesis rate of proteins from pathogenic CAG repeat transcripts, thereby decreasing the initiation of amyloidogenesis in CAG-repeat diseases.
HUMAN MOLECULAR GENETICS
(2021)
Article
Nanoscience & Nanotechnology
B. S. Joshi, D. Ortiz, I. S. Zuhorn
Summary: Extracellular vesicles (EVs) serve as biological delivery vehicles for therapeutic cargo, with key technologies including loading, surface functionalization, and cargo release methods. Challenges for clinical translation of EV-mediated drug delivery are also discussed.
MATERIALS TODAY NANO
(2021)
Article
Biology
Wouter Huiting, Suzanne L. Dekker, Joris C. J. van der Lienden, Rafaella Mergener, Maiara K. Musskopf, Gabriel Furtado, Emma Gerrits, David Coit, Mehrnoosh Oghbaie, Luciano H. Di Stefano, Hein Schepers, Maria A. W. H. Van Waarde-Verhagen, Suzanne Couzijn, Lara Barazzuol, John LaCava, Harm H. Kampinga, Steven Bergink
Summary: Loss of ATM or other genotoxic conditions can lead to increased protein aggregation due to overload of chaperone systems, which decreases the cell-intrinsic threshold for proteins to aggregate.
Article
Biochemistry & Molecular Biology
Yuanke Liang, Danielle Voshart, Judith T. M. L. Paridaen, Nynke Oosterhof, Dong Liang, Arun Thiruvalluvan, Inge S. Zuhorn, Wilfred F. A. den Dunnen, Guojun Zhang, Haoyu Lin, Lara Barazzuol, Frank A. E. Kruyt
Summary: This study reveals the important role of the cell adhesion molecule CD146 in regulating the aggressiveness of the brain tumor Glioblastoma (GBM). Elevated CD146 levels are correlated with higher tumor grades, poor response to treatment, and worse overall survival. CD146 overexpression enhances mesenchymal and invasive properties, stemness, and radiotherapy resistance in GBM. These findings suggest that CD146 could be a potential therapeutic target for GBM treatment.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Cell Biology
E. F. Elsiena Kuiper, Paola Gallardo, Tessa Bergsma, Muriel Mari, Maiara Kolbe Musskopf, Jeroen Kuipers, Ben N. G. Giepmans, Anton Steen, Harm H. Kampinga, Liesbeth M. Veenhoff, Steven Bergink
Summary: DNAJB6, a molecular chaperone, plays a role in quality control during the biogenesis of nuclear pore complexes, specifically by preventing aggregation of intrinsically disordered FG-Nups.
NATURE CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Natalia Orti-Casan, Inge S. Zuhorn, Petrus J. W. Naude, Peter P. De Deyn, Pauline E. M. van Schaik, Harald Wajant, Ulrich L. M. Eisel
Summary: This study investigated the effects of stimulating TNFR2 with a TNFR2 agonist (NewStar2) in an AD mouse model. The results demonstrated that activation of TNFR2 reduced amyloid beta deposition and expression of beta-secretase 1, increased microglial and astrocytic activation, promoted the uptake and degradation of A beta, and improved cognitive functions. These findings suggest that TNFR2 stimulation might be a potential treatment for AD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Mario Mauthe, Harm H. Kampinga, Mark S. Hipp, Fulvio Reggiori
Summary: Aggrephagy is the process of selective lysosomal transport and turnover of cytoplasmic protein aggregates by macro-autophagy. Protein aggregates are polyubiquitinated and sequestered by autophagosomes. Soluble selective autophagy receptors (SARs) play a central role in aggrephagy by physically binding to ubiquitin and the autophagy machinery. Understanding the mechanism of aggrephagy can potentially lead to therapeutic strategies for preventing the buildup of potentially toxic protein aggregates.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Engineering, Biomedical
Aldy Aliyandi, Catharina Reker-Smit, Inge S. Zuhorn, Anna Salvati
Summary: Targeted drug delivery relies on the specific interaction between nanocarriers and cell surface receptors for efficient internalization. By using cell surface biotinylation, we identified the receptors mediating nanoparticle uptake. Vitronectin corona was found to enhance the uptake of nanoparticles in brain and liver endothelial cells by targeting integrin receptors.
ACTA BIOMATERIALIA
(2023)
Article
Pharmacology & Pharmacy
Bhagyashree S. Joshi, Hector Garcia Romeu, Aldy Aliyandi, Marcel P. de Vries, Inge S. Zuhorn
Summary: Cell-derived extracellular vesicles are considered as promising candidates for in vivo drug delivery due to their ability to enter cells and deliver cargo. This study investigated the transmission mechanism of DNAJB6 in EVs using HEK293T cells.
Article
Biochemical Research Methods
Bhagyashree S. Joshi, Inge S. Zuhorn
Summary: In this article, a protocol for preparing small extracellular vesicles (sEVs) enriched in the chaperone protein DNAJB6 using genetic engineering techniques is presented. The steps to prepare cell lines overexpressing DNAJB6, as well as the isolation and characterization of sEVs from cell conditioned media, are described. Additionally, assays to examine the effects of DNAJB6-loaded sEVs on protein aggregation in Huntington's disease cellular models are discussed. The protocol can be applied to study protein aggregation in other neurodegenerative disorders or extended to investigate other therapeutic proteins. For complete details on the use and execution of this protocol, please refer to Joshi et al. (2021).
Review
Cell & Tissue Engineering
Alejandro Reina-Mahecha, Martine J. Beers, Hugo C. van der Veen, Inge S. Zuhorn, Theo G. van Kooten, Prashant K. Sharma
Summary: This review summarizes the current understanding of bioreactors and their potential use in cartilage tissue engineering, with a focus on induced pluripotent stem cells (iPSCs). Bioreactors play a crucial role in simulating the joint cavity niche, promoting cell differentiation, and maintaining homeostasis in cartilage tissue engineering. Incorporating iPSCs and bioreactors shows promise for advancing the field and translating these approaches into clinical applications.
TISSUE ENGINEERING AND REGENERATIVE MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Pauline E. M. van Schaik, Inge S. Zuhorn, Wia Baron
Summary: Multiple sclerosis is a neuroinflammatory and neurodegenerative disease with unknown etiology that can be characterized by demyelinated lesions. Remyelination is essential for axonal survival and functional recovery, but fibronectin inhibits this process. The blood-brain barrier poses a challenge for delivering therapeutic interventions to the lesions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Gastroenterology & Hepatology
Noortje Ijssennagger, Kristel S. van Rooijen, Stefania Magnusdottir, Jose M. Ramos Pittol, Ellen C. L. Willemsen, Marcel R. de Zoete, Matthijs J. D. Baars, Paul B. Stege, Carolina Colliva, Roberto Pellicciari, Sameh A. Youssef, Alain de Bruin, Yvonne Vercoulen, Folkert Kuipers, Saskia W. C. van Mil
Summary: This study highlights the importance of liver-to-gut communication for intestinal health, with a focus on colon functioning. Elimination of Fxr in the liver significantly affects colonic gene expression and enhances the protective capacity of the mucus barrier.