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Keywords = cell-derived nanovesicles

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31 pages, 4179 KiB  
Review
Plant-Derived Vesicle-like Nanoparticles: Pioneering Sustainable and Effective Approaches for Tissue Repair and Regeneration
by Qinjing Wang, Zhijie Huang, Jiming Guo, Weixing Chen, Min Wang, Yue Ming, Hongyu Liu, Mingshu Huang, Yisheng Huang, Zhengming Tang and Bo Jia
Biomolecules 2025, 15(8), 1055; https://doi.org/10.3390/biom15081055 - 22 Jul 2025
Viewed by 448
Abstract
Plant-derived vesicle-like nanoparticles (PDVLNs) are bioactive nanovesicles secreted by plant cells, emerging as a novel therapeutic tool for tissue repair and regeneration due to their low immunogenicity, intrinsic bioactivity, and potential as drug delivery carriers. This review examines PDVLNs’ biogenesis mechanisms, isolation techniques, [...] Read more.
Plant-derived vesicle-like nanoparticles (PDVLNs) are bioactive nanovesicles secreted by plant cells, emerging as a novel therapeutic tool for tissue repair and regeneration due to their low immunogenicity, intrinsic bioactivity, and potential as drug delivery carriers. This review examines PDVLNs’ biogenesis mechanisms, isolation techniques, and compositional diversity, emphasizing their roles in promoting essential regenerative processes—cell proliferation, differentiation, migration, immune modulation, and angiogenesis. We explore their therapeutic applications across multiple tissue types, including skin, bone, neural, liver, gastrointestinal, cardiovascular, and dental tissues, using both natural and engineered PDVLNs in various disease models. Compared to mammalian exosomes, PDVLNs offer advantages such as reduced immune rejection and ethical concerns, enhancing their sustainability and appeal for regenerative medicine. However, challenges in clinical translation, including scalability, standardization, and safety remain. This paper consolidates current knowledge on PDVLNs, highlighting their versatility and providing insights into engineering strategies to optimize efficacy, ultimately outlining future research directions to advance their clinical potential. Plant vesicle-like nanoparticles (PDVLNs) may become a new avenue for the treatment of tissue injury, promoting tissue repair and regeneration through their intrinsic bioactivity or as drug delivery carriers. In addition, PDVLNs can be engineered and modified to achieve better results. Full article
(This article belongs to the Section Natural and Bio-derived Molecules)
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23 pages, 6291 KiB  
Article
Application of Standardized Rosa damascena Stem Cell-Derived Exosomes in Dermatological Wound Healing and Scar Management: A Retrospective Case-Series Study with Long-Term Outcome Assessment
by Lidia Majewska, Agnieszka Kondraciuk, Karolina Dorosz and Agnieszka Budzyńska
Pharmaceutics 2025, 17(7), 910; https://doi.org/10.3390/pharmaceutics17070910 - 14 Jul 2025
Cited by 2 | Viewed by 705
Abstract
Background: Scar formation and impaired wound healing represent significant challenges in dermatology and aesthetic medicine, with limited effective treatment options currently available. Objectives: To evaluate the efficacy and long-term outcomes of Damask rose stem-cell-derived exosome (RSCE) therapy in the management of [...] Read more.
Background: Scar formation and impaired wound healing represent significant challenges in dermatology and aesthetic medicine, with limited effective treatment options currently available. Objectives: To evaluate the efficacy and long-term outcomes of Damask rose stem-cell-derived exosome (RSCE) therapy in the management of diverse dermatological conditions, including traumatic wounds, surgical scars, and atrophic acne scars. Methods: We conducted a case series study from June 2023 to November 2024, documenting four cases with different types of skin damage treated with lyophilized RSCE products. Treatment protocols included a variety of delivery methods such as topical application, microneedling, and post-procedure care. Follow-up assessments were performed at intervals ranging from 7 days to 10 months. Results: All patients demonstrated significant improvements in scar appearance, skin elasticity, hydration, and overall tissue quality. In traumatic facial injury, RSCE therapy facilitated reduction in scar contracture and improved functional outcomes. For atrophic acne scars, comparative treatment of facial sides showed enhanced results with RSCE addition. Acute wounds exhibited accelerated healing with reduced inflammation, while chronic wounds demonstrated improved epithelialization and long-term scar quality. Conclusions: This case series provides preliminary evidence suggesting that RSCE therapy may offer significant benefits in wound healing and scar management. The observed improvements in tissue regeneration, inflammatory modulation, and long-term aesthetic outcomes warrant further investigation through controlled clinical trials. Full article
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18 pages, 3320 KiB  
Article
Isolation and Bioactive Characterization of Berberis kaschgarica Rupr-Derived Exosome-Like Nanovesicles: Exploring Therapeutic Potential in Atherosclerosis Pathogenesis
by Dilihuma Dilimulati, Nuerbiye Nueraihemaiti, Alhar Baishan, Sendaer Hailati, Alifeiye Aikebaier, Yipaerguli Paerhati and Wenting Zhou
Biology 2025, 14(6), 726; https://doi.org/10.3390/biology14060726 - 19 Jun 2025
Viewed by 564
Abstract
Berberis kaschgarica Rupr.-derived exosome-like nanovesicles (BELNs), a type of plant-derived extracellular vesicle, consist of proteins, lipids, and nucleic acids. In this research, we employed differential centrifugation and ultracentrifugation techniques to isolate and purify BELNs. Subsequently, we conducted a comprehensive multi-omics analysis to systematically [...] Read more.
Berberis kaschgarica Rupr.-derived exosome-like nanovesicles (BELNs), a type of plant-derived extracellular vesicle, consist of proteins, lipids, and nucleic acids. In this research, we employed differential centrifugation and ultracentrifugation techniques to isolate and purify BELNs. Subsequently, we conducted a comprehensive multi-omics analysis to systematically determine their physicochemical properties. Experiments were conducted in vitro with Human Umbilical Vein Endothelial Cells (HUVECs) to verify the therapeutic impact of BELNSs on atherosclerosis. The isolated BELNs exhibited a distinctive teacup-shaped exosome morphology. The extraction yield was approximately 2.1 × 1013 particles per milliliter, and the average particle size was measured to be 179.1 nm. These nanovesicles were lipid-rich. The protein content predominantly comprised cytoplasmic proteins. In-depth analysis revealed the presence of five highly conserved plant microRNAs: miR166, miR156, miR399, miR171, and miR395. These miRNAs are involved in regulating plant growth and responses to both biotic and abiotic stresses. Functional assays demonstrated that Berberis kaschgarica Rupr.-derived exosome-like nanovesicles substantially decreased the lipid deposition in HUVECs that was triggered by Palmitic Acid (PA). This research establishes the inaugural utilization of multi-omics platforms to systematically elucidate the bioactivity profile of BELNs from Berberis kaschgarica Rupr., thereby laying the groundwork for advancing its therapeutic potential. Full article
(This article belongs to the Special Issue Plant Natural Products: Mechanisms of Action for Promoting Health)
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15 pages, 6119 KiB  
Article
A Bionic “Trojan Horse”-like Nanovesicle Delivery System Hybridized with BCG Cytoplasmic Membrane and Melanoma Cell Membrane for Cancer Immunotherapy
by Yuai Xiao, Kexin Chen, Tianchi Hu, Yuchong Wang, Jing Wang, Chuan Lv, Jianguo Xu, Xinyi Zhang, Ang Li, Bingdi Chen, Ji Zhu, Minliang Wu and Chunyu Xue
Pharmaceutics 2025, 17(4), 507; https://doi.org/10.3390/pharmaceutics17040507 - 11 Apr 2025
Viewed by 786
Abstract
Background: In recent years, tumor vaccines have demonstrated unexpected success in cancer treatment. However, it still faces several challenges, including insufficient antigen and adjuvant delivery, unsuitable antigen delivery system, and inadequate antigen-presenting cell (APC) maturation. Antigenic adjuvant co-delivery tactics could be one [...] Read more.
Background: In recent years, tumor vaccines have demonstrated unexpected success in cancer treatment. However, it still faces several challenges, including insufficient antigen and adjuvant delivery, unsuitable antigen delivery system, and inadequate antigen-presenting cell (APC) maturation. Antigenic adjuvant co-delivery tactics could be one way to enhance APC maturation. Methods: Membrane-fused nanovesicles were synthesized by separating melanoma cell membranes from BCG cytoplasmic membranes. Dynamic light scattering and transmission electron microscopy were used for measuring the vesicles’ size and shape. The uptake of vesicles by mouse bone marrow-derived dendritic cells and the activation of DC cells by vesicles were verified in vitro. In order to further confirm the material’s capacity to activate the immune system and its ability to inhibit tumor growth, the activation of DC and T cells in mouse draining lymph nodes and the concentration of anti-tumor cytokines were measured. Results: The hybrid vesicles were homogeneous in size and could facilitate phagocytosis by dendritic cells (DCs). They could also effectively activate DCs and T cells in vitro and in vivo, eliciting anti-tumor immunity. Moreover, the vesicles demonstrated satisfying biosafety with no major side effects. Conclusions: Motivated by the myth of the Trojan Horse, we created an antigen-adjuvant-integrated nanovesicle that merges the BCG cytomembrane with the tumor cell membrane, which can achieve immune cell stimulation and tumor antigen delivery simultaneously. In conclusion, these findings support the potential application of dual-membrane fusion nanovesicles as tumor vaccines. Full article
(This article belongs to the Section Clinical Pharmaceutics)
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33 pages, 1894 KiB  
Review
Bioprinted Hydrogels as Vehicles for the Application of Extracellular Vesicles in Regenerative Medicine
by Marta Camacho-Cardenosa, Victoria Pulido-Escribano, Guadalupe Estrella-Guisado, Gabriel Dorado, Aura D. Herrera-Martínez, María Ángeles Gálvez-Moreno and Antonio Casado-Díaz
Gels 2025, 11(3), 191; https://doi.org/10.3390/gels11030191 - 8 Mar 2025
Viewed by 1379
Abstract
Three-dimensional bioprinting is a new advance in tissue engineering and regenerative medicine. Bioprinting allows manufacturing three-dimensional (3D) structures that mimic tissues or organs. The bioinks used are mainly made of natural or synthetic polymers that must be biocompatible, printable, and biodegradable. These bioinks [...] Read more.
Three-dimensional bioprinting is a new advance in tissue engineering and regenerative medicine. Bioprinting allows manufacturing three-dimensional (3D) structures that mimic tissues or organs. The bioinks used are mainly made of natural or synthetic polymers that must be biocompatible, printable, and biodegradable. These bioinks may incorporate progenitor cells, favoring graft implantation and regeneration of injured tissues. However, the natures of biomaterials, bioprinting processes, a lack of vascularization, and immune responses are factors that limit the viability and functionality of implanted cells and the regeneration of damaged tissues. These limitations can be addressed by incorporating extracellular vesicles (EV) into bioinks. Indeed, EV from progenitor cells may have regenerative capacities, being similar to those of their source cells. Therefore, their combinations with biomaterials can be used in cell-free therapies. Likewise, they can complement the manufacture of bioinks by increasing the viability, differentiation, and regenerative ability of incorporated cells. Thus, the main objective of this review is to show how the use of 3D bioprinting technology can be used for the application of EV in regenerative medicine by incorporating these nanovesicles into hydrogels used as bioinks. To this end, the latest advances derived from in vitro and in vivo studies have been described. Together, these studies show the high therapeutic potential of this strategy in regenerative medicine. Full article
(This article belongs to the Special Issue Gels: 10th Anniversary)
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25 pages, 33164 KiB  
Article
Poria cocos-Derived Exosome-like Nanovesicles Alleviate Metabolic Dysfunction-Associated Fatty Liver Disease by Promoting Mitophagy and Inhibiting NLRP3 Inflammasome Activation
by Tao Wang, Jun Zhao, Qiu-Yi Li, Hui-Qiong Yang, Min Li, Rong Duan, Mei Zhang, Yan Qi, Jie Yu and Xing-Xin Yang
Int. J. Mol. Sci. 2025, 26(5), 2253; https://doi.org/10.3390/ijms26052253 - 3 Mar 2025
Cited by 2 | Viewed by 1902
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) affects approximately one-quarter of the world’s adult population, and no effective therapeutic drugs are available. Poria cocos is a fungus used as a herb and food nutrient for centuries as well as for MAFLD treatment. Exosome-like nanovesicles [...] Read more.
Metabolic dysfunction-associated fatty liver disease (MAFLD) affects approximately one-quarter of the world’s adult population, and no effective therapeutic drugs are available. Poria cocos is a fungus used as a herb and food nutrient for centuries as well as for MAFLD treatment. Exosome-like nanovesicles have many pharmacological activities; however, studies on the effects of Poria cocos-derived exosome-like nanovesicles (PCELNs) on MAFLD are lacking. Therefore, our study aimed at identifying the effects and mechanism of action of PCELNs on MAFLD. PCELNs were isolated by ultracentrifugation and their morphology was characterized, such as particle size, zeta potential, protein distributions, as well as lipid and miRNA compositions. Then, the absorption and distribution of PCELNs were observed in vivo and in vitro. Finally, L02 cell steatosis model induced by fat emulsion and MAFLD mouse model induced by high-fat diet (HFD) were used to evaluate the effect and mechanism of PCELNs on MAFLD. PCELNs were membrane structured vesicles, with a particle size of 161.4 ± 1.7 nm, a zeta potential of −3.20 ± 0.37 mV, and contained a range of proteins, lipids, and miRNAs. PCELNs were absorbed by L02 cells and targeted the liver and spleen after intraperitoneal injection. PCELNs inhibited body weight gain and improved the index of heart, liver, spleen, and various fats, as well as decreased lipid accumulation and lipid level. They also protected mitochondrial ultrastructure and regulated oxidative stress and energy metabolism disorder. Furthermore, PCELNs increased PTEN induced kinase 1 (PINK1), E3 ubiquitin ligase (Parkin) and microtubule associated protein light chain-3 (LC3) protein expression in the liver, reduced oxidized mitochondrial DNA (Ox-mtDNA) content in mitochondria and cytoplasm of the liver, reduced nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3), pro-cysteinyl aspartate specific proteinase-1 (caspase-1), cleared-caspase-1, and mature-interleukin-1β (IL-1β) protein expression in the liver, and reduced the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and interleukin-18 (IL-18) in serum and liver. In conclusion, we demonstrated that PCELNs may alleviate HFD-induced MAFLD by promoting mitochondrial autophagy and inhibiting NLRP3 inflammasome activation. Full article
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30 pages, 7611 KiB  
Article
Design and Development of Natural-Product-Derived Nanoassemblies and Their Interactions with Alpha Synuclein
by Ipsita A. Banerjee, Amrita Das, Mary A. Biggs, Chau Anh N. Phan, Liana R. Cutter and Alexandra R. Ren
Biomimetics 2025, 10(2), 82; https://doi.org/10.3390/biomimetics10020082 - 28 Jan 2025
Viewed by 1475
Abstract
Biomimetic nanoassemblies derived from natural products are considered promising nanomaterials due to their self-assembling ability and their favorable interactions with biological molecules leading to their numerous applications as therapeutic agents or as molecular probes. In this work, we have created peptide nanoconjugates of [...] Read more.
Biomimetic nanoassemblies derived from natural products are considered promising nanomaterials due to their self-assembling ability and their favorable interactions with biological molecules leading to their numerous applications as therapeutic agents or as molecular probes. In this work, we have created peptide nanoconjugates of two natural products, β-Boswellic acid (BA) and β-glycyrrhetinic acid (GH). Both BA and GH are known for their medicinal value, including their role as strong antioxidants, anti-inflammatory, neuroprotective and as anti-tumor agents. To enhance the bioavailability of these molecules, they were functionalized with three short peptides (YYIVS, MPDAHL and GSGGL) to create six conjugates with amphiphilic structures capable of facile self-assembly. The peptides were also derived from natural sources and have been known to display antioxidant activity. Depending upon the conjugate, nanofibers, nanovesicles or a mixture of both were formed upon self-assembly. The binding interactions of the nanoconjugates with α-Synuclein, a protein implicated in Parkinson’s disease (PD) was examined through in silico studies and FTIR, circular dichroism and imaging studies. Our results indicated that the nanoassemblies interacted with alpha-synuclein fibrils efficaciously. Furthermore, the nanoassemblies were found to demonstrate high viability in the presence of microglial cells, and were found to enhance the uptake and interactions of α-Synuclein with microglial cells. The nanoconjugates designed in this work may be potentially utilized as vectors for peptide-based drug delivery or for other therapeutic applications. Full article
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31 pages, 1806 KiB  
Review
Emerging Strategies for Revascularization: Use of Cell-Derived Extracellular Vesicles and Artificial Nanovesicles in Critical Limb Ischemia
by Vijay Murali Ravi Mythili, Ramya Lakshmi Rajendran, Raksa Arun, Vasanth Kanth Thasma Loganathbabu, Danyal Reyaz, ArulJothi Kandasamy Nagarajan, Byeong-Cheol Ahn and Prakash Gangadaran
Bioengineering 2025, 12(1), 92; https://doi.org/10.3390/bioengineering12010092 - 20 Jan 2025
Cited by 2 | Viewed by 1853
Abstract
Critical limb ischemia (CLI) poses a substantial and intricate challenge in vascular medicine, necessitating the development of innovative therapeutic strategies to address its multifaceted pathophysiology. Conventional revascularization approaches often fail to adequately address the complexity of CLI, necessitating the identification of alternative methodologies. [...] Read more.
Critical limb ischemia (CLI) poses a substantial and intricate challenge in vascular medicine, necessitating the development of innovative therapeutic strategies to address its multifaceted pathophysiology. Conventional revascularization approaches often fail to adequately address the complexity of CLI, necessitating the identification of alternative methodologies. This review explores uncharted territory beyond traditional therapies, focusing on the potential of two distinct yet interrelated entities: cell-derived extracellular vesicles (EVs) and artificial nanovesicles. Cell-derived EVs are small membranous structures naturally released by cells, and artificial nanovesicles are artificially engineered nanosized vesicles. Both these vesicles represent promising avenues for therapeutic intervention. They act as carriers of bioactive cargo, including proteins, nucleic acids, and lipids, that can modulate intricate cellular responses associated with ischemic tissue repair and angiogenesis. This review also assesses the evolving landscape of CLI revascularization through the unique perspective of cell-derived EVs and artificial nanovesicles. The review spans the spectrum from early preclinical investigations to the latest translational advancements, providing a comprehensive overview of the current state of research in this emerging field. These groundbreaking vesicle therapies hold immense potential for revolutionizing CLI treatment paradigms. Full article
(This article belongs to the Special Issue Innovations in Regenerative Therapy: Cell and Cell-Free Approaches)
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33 pages, 9381 KiB  
Article
Nanoformulation of Spirooxindole and Methods for Treating Hepatocellular Carcinoma
by Assem Barakat, Fardous F. El-Senduny, Mohammad Shahidul Islam, Abdullah Mohammed Al-Majid, Yaseen A. M. M. Elshaier, Eman A. Mazyed and Farid A. Badria
Pharmaceutics 2025, 17(1), 93; https://doi.org/10.3390/pharmaceutics17010093 - 12 Jan 2025
Viewed by 1041
Abstract
Objectives: This in vivo study introduces a newly developed spirooxindole derivative that is deemed safe and effective as a potential targeted therapy for various cancers. Methods: Extensive in vivo investigations, including histopathology, immunohistochemistry, and molecular biology, validated its potential for further preclinical and [...] Read more.
Objectives: This in vivo study introduces a newly developed spirooxindole derivative that is deemed safe and effective as a potential targeted therapy for various cancers. Methods: Extensive in vivo investigations, including histopathology, immunohistochemistry, and molecular biology, validated its potential for further preclinical and clinical exploration, necessitating comprehensive examinations of its bioavailability, pharmacodynamics, and pharmacokinetics. Additionally, this study involves the development of a commercially viable proniosomal drug delivery system for the compound, facilitating controlled drug release. Results: The data revealed efficacy of spirooxindole derivative in halting the progression of liver cancer, metastasis, and portal vein thrombosis, with potential implications for enhancing regeneration and recovery of early-stage cancer cells in multiple organs, thereby improving recovery rates and remission among cancer patients. The proniosomes, loaded with the compound, exhibited high entrapment efficiency and prolonged drug release rates of up to 12 h in vitro. The optimized formula demonstrated superior drug release percentages and stability compared to conventional niosomes. Further analysis via FTIR and DSC confirmed the absence of chemical interactions and proper entrapment of the compound within the nanovesicles, indicating a stable and effective drug delivery system. Conclusions: This study presents a novel, safe, and effective chemical entity of spirooxindole derivatives for further preclinical and clinical studies. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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20 pages, 8670 KiB  
Article
Cell Membrane- and Extracellular Vesicle-Coated Chitosan Methacrylate-Tripolyphosphate Nanoparticles for RNA Delivery
by Wen Jie Melvin Liew, Syed Abdullah Alkaff, Sheng Yuan Leong, Marin Zhen Lin Yee, Han Wei Hou and Bertrand Czarny
Int. J. Mol. Sci. 2024, 25(24), 13724; https://doi.org/10.3390/ijms252413724 - 23 Dec 2024
Cited by 2 | Viewed by 2311
Abstract
mRNA-based vaccines against the COVID-19 pandemic have propelled the use of nucleic acids for drug delivery. Conventional lipid-based carriers, such as liposomes and nanolipogels, effectively encapsulate and deliver RNA but are hindered by issues such as premature burst release and immunogenicity. To address [...] Read more.
mRNA-based vaccines against the COVID-19 pandemic have propelled the use of nucleic acids for drug delivery. Conventional lipid-based carriers, such as liposomes and nanolipogels, effectively encapsulate and deliver RNA but are hindered by issues such as premature burst release and immunogenicity. To address these challenges, cell membrane-coated nanoparticles offer a promising alternative. We developed a novel nanoparticle system using chitosan methacrylate-tripolyphosphate (CMATPP), which capitalizes on interactions involving membrane proteins at biointerfaces. Ionic crosslinking between chitosan methacrylate and tripolyphosphate facilitates the formation of nanoparticles amenable to coating with red blood cell (RBC) membranes, extracellular vesicles (EVs), and cell-derived nanovesicles (CDNs). Coating CMATPP nanoparticles with RBC membranes effectively mitigated the initial burst release of encapsulated small interfering RNA (siRNA), sustaining controlled release while preserving membrane proteins. This concept was extended to EVs, where CMATPP nanoparticles and CDNs were incorporated into a microfluidic device and subjected to electroporation to create hybrid CDN-CMATPP nanoparticles. Our findings demonstrate that CMATPP nanoparticles are a robust siRNA delivery system with suppressed burst release and enhanced membrane properties conferred by cell or vesicle membranes. Furthermore, the adaptation of the CDN-CMATPP nanoparticle formation in a microfluidic device suggests its potential for personalized therapies using diverse cell sources and increased throughput via automation. This study underscores the versatility and efficacy of CMATPP nanoparticles in RNA delivery, offering a pathway towards advanced therapeutic strategies that utilize biomimetic principles and microfluidic technologies. Full article
(This article belongs to the Special Issue Biomaterials for Drug Delivery and Advanced Therapies)
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15 pages, 2850 KiB  
Article
Gold Kiwi-Derived Nanovesicles Mitigate Ultraviolet-Induced Photoaging and Enhance Osteogenic Differentiation in Bone Marrow Mesenchymal Stem Cells
by Doyeon Kim, Chanho Lee, Manho Kim and Ju Hyun Park
Antioxidants 2024, 13(12), 1474; https://doi.org/10.3390/antiox13121474 - 29 Nov 2024
Cited by 1 | Viewed by 1112
Abstract
Bone marrow mesenchymal stem cells (BM-MSCs) play a crucial role in bone formation through their ability to differentiate into osteoblasts. Aging, however, detrimentally affects the differentiation and proliferation capacities of BM-MSCs, consequently impairing bone regeneration. Thus, mitigating the aging effects on BM-MSCs is [...] Read more.
Bone marrow mesenchymal stem cells (BM-MSCs) play a crucial role in bone formation through their ability to differentiate into osteoblasts. Aging, however, detrimentally affects the differentiation and proliferation capacities of BM-MSCs, consequently impairing bone regeneration. Thus, mitigating the aging effects on BM-MSCs is vital for addressing bone-related pathologies. In this study, we demonstrate that extracellular nanovesicles isolated from gold kiwi (GK-NVs) protect human BM-MSCs from ultraviolet (UV)-induced photoaging, thereby alleviating aging-related impairments in cellular functions that are crucial for bone homeostasis. Notably, GK-NVs were efficiently taken up by BM-MSCs without causing cytotoxicity. GK-NVs reduced intracellular reactive oxygen species (ROS) levels upon UV irradiation, restoring impaired proliferation and migration capabilities. Furthermore, GK-NVs corrected the skewed differentiation capacities of UV-irradiated BM-MSCs by enhancing osteoblast differentiation, as evidenced by the increased expression in osteoblast-specific genes and the calcium deposition, and by reducing adipocyte differentiation, as indicated by the decreased lipid droplet formation. These findings position GK-NVs as a promising biomaterial for the treatment of bone-related diseases such as osteoporosis. Full article
(This article belongs to the Special Issue Antioxidants as Anti-Aging Interventions)
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26 pages, 2820 KiB  
Review
The Opportunities and Challenges of Mesenchymal Stem Cells-Derived Exosomes in Theranostics and Regenerative Medicine
by Sachin Yadav, Pritiprasanna Maity and Kausik Kapat
Cells 2024, 13(23), 1956; https://doi.org/10.3390/cells13231956 - 25 Nov 2024
Cited by 8 | Viewed by 3305
Abstract
Cell-secreted nanovesicles of endosomal origin, called exosomes, are vital for mediating intracellular communication. As local or distal transporters of intracellular cargo, they reflect the unique characteristics of secretory cells and establish cell-specific interactions via characteristic surface proteins and receptors. With the advent of [...] Read more.
Cell-secreted nanovesicles of endosomal origin, called exosomes, are vital for mediating intracellular communication. As local or distal transporters of intracellular cargo, they reflect the unique characteristics of secretory cells and establish cell-specific interactions via characteristic surface proteins and receptors. With the advent of rapid isolation, purification, and identification techniques, exosomes have become an attractive choice for disease diagnosis (exosomal content as biomarkers), cell-free therapy, and tissue regeneration. Mesenchymal stem cell (MSC)-derived exosomes (MSC-exosomes) display angiogenic, immune-modulatory, and other therapeutic effects crucial for cytoprotection, ischemic wound repair, myocardial regeneration, etc. The primary focus of this review is to highlight the widespread application of MSC-exosomes in therapeutics, theranostics, and tissue regeneration. After a brief introduction of exosome properties, biogenesis, isolation, and functions, recent studies on therapeutic and regenerative applications of MSC-exosomes are described, focusing on bone, cartilage, periodontal, cardiovascular, skin, and nerve regeneration. Finally, the review highlights the theranostic potential of exosomes followed by challenges, summary, and outlook. Full article
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18 pages, 5723 KiB  
Article
Development and Biological Characterization of Cancer Biomimetic Membrane Nanovesicles for Enhancing Therapy Efficacy in Human Glioblastoma Cells
by Martina Massarotti, Paola Corna, Aromita Mallik, Gloria Milanesi, Claudio Casali, Lorenzo Magrassi and Sergio Comincini
Nanomaterials 2024, 14(22), 1779; https://doi.org/10.3390/nano14221779 - 5 Nov 2024
Cited by 1 | Viewed by 1296
Abstract
As nanocarriers of a new generation, biomimetic nanovesicles are an emerging class of therapeutic tools whose surface is integrated or fabricated with biomaterials capable of mimicking the biological features and functions of native cells. Thanks to this, biomimetic nanovesicles, in particular, those made [...] Read more.
As nanocarriers of a new generation, biomimetic nanovesicles are an emerging class of therapeutic tools whose surface is integrated or fabricated with biomaterials capable of mimicking the biological features and functions of native cells. Thanks to this, biomimetic nanovesicles, in particular, those made by plasma membrane moieties, possess greatly improved biocompatibility, high target specificity, a long retention time, and minimal undesired immune responses. For these reasons, a multitude of progenitor cells including cancer ones were employed as templates to generate biomimetic or membrane-camouflaged nanovesicles hosting different therapeutic compounds. In this contribution, different membrane-derived biomimetic vesicles (M-NVs) were generated by osmotic lysis or plasma membrane isolation approaches from normal and cancer cell lines and assayed against in vitro models of human glioblastoma. M-NVs were compared in their cellular internalization degrees of DNA and proteins, morphologically and molecularly characterized, expressing an extracellular membrane-associated marker. Then, Rose Bengal (RB), a photoactivable drug characterized by a relatively low cellular uptake, was incorporated into nascent glioblastoma-derived M-NVs and finally administered to homotypic receiving cells, showing an increased degree of internalization as well as induced cytotoxic effects, even in the absence of photodynamic direct stimulation. Similar results were also obtained assaying lyophilized M-NVs loaded with RB. In conclusion, M-NVs generated by cell membranes effectively deliver several cargoes, including therapeutic molecules, maintain functionality after lyophilization, and show significant internalization effects, making them a promising strategy for therapeutic applications against human glioblastoma cells. Full article
(This article belongs to the Special Issue The Study of the Effects of Nanoparticles on Human Cells)
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13 pages, 1957 KiB  
Article
In Silico Design of Novel EpCAM-Binding Aptamers for Targeted Delivery of RNA Therapeutics
by Julia Driscoll, Piyush Gondaliya, Abbye Ziemer, Irene K. Yan, Yash Gupta and Tushar Patel
Nanomaterials 2024, 14(21), 1727; https://doi.org/10.3390/nano14211727 - 29 Oct 2024
Cited by 1 | Viewed by 1794
Abstract
Aptamers are short DNA or RNA sequences that adopt 3D structures and can bind to protein targets with high binding affinity and specificity. Aptamers exhibit excellent tissue penetration, are inexpensive to produce, and can be internalized by cells. Therefore, aptamers are attractive targeting [...] Read more.
Aptamers are short DNA or RNA sequences that adopt 3D structures and can bind to protein targets with high binding affinity and specificity. Aptamers exhibit excellent tissue penetration, are inexpensive to produce, and can be internalized by cells. Therefore, aptamers are attractive targeting ligands to direct the delivery of theranostic agents to the desired cells. Epithelial cell adhesion molecule (EpCAM) is a tumor-associated antigen that is aberrantly overexpressed on many epithelial-derived cancers, including on cholangiocarcinoma (CCA) cells. Its expression on treatment-resistant cancer stem cells, along with its abundance in the CCA tumor microenvironment, highlights the need to develop EpCAM-targeted therapies for CCA. Herein, an in silico approach was used to design and screen DNA aptamers capable of binding to the EpCAM monomer and homodimer. Two aptamers, PLD01 and PLD02, met the selection criteria and were validated in vitro. Both aptamers exhibited high affinity for EpCAM+ CCA cells, with negligible binding to EpCAM- leukemia cells. Modified versions of PLD01 and PLD02 were successfully incorporated into the membranes of milk-derived nanovesicles. PLD01-functionalized nanovesicles enabled EpCAM-targeted delivery of the therapeutic cargo to CCA cells. In summary, these EpCAM-targeting aptamers can be utilized to direct the delivery of theranostic agents to EpCAM-expressing cells. Full article
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22 pages, 5741 KiB  
Article
The Therapeutic Potential of Exosomes vs. Matrix-Bound Nanovesicles from Human Umbilical Cord Mesenchymal Stromal Cells in Osteoarthritis Treatment
by Timofey O. Klyucherev, Maria A. Peshkova, Daria P. Revokatova, Natalia B. Serejnikova, Nafisa M. Fayzullina, Alexey L. Fayzullin, Boris P. Ershov, Yana I. Khristidis, Irina I. Vlasova, Nastasia V. Kosheleva, Andrey A. Svistunov and Peter S. Timashev
Int. J. Mol. Sci. 2024, 25(21), 11564; https://doi.org/10.3390/ijms252111564 - 28 Oct 2024
Cited by 3 | Viewed by 3904
Abstract
Osteoarthritis (OA) is a degenerative joint disease with limited therapeutic options, where inflammation plays a critical role in disease progression. Extracellular vesicles (EV) derived from mesenchymal stromal cells (MSC) have shown potential as a therapeutic approach for OA by modulating inflammation and alleviating [...] Read more.
Osteoarthritis (OA) is a degenerative joint disease with limited therapeutic options, where inflammation plays a critical role in disease progression. Extracellular vesicles (EV) derived from mesenchymal stromal cells (MSC) have shown potential as a therapeutic approach for OA by modulating inflammation and alleviating degenerative processes in the joint. This study evaluated the therapeutic effects for the treatment of OA of two types of EV—exosomes and matrix-bound nanovesicles (MBV)—both derived from the human umbilical cord MSC (UC-MSC) via differential ultracentrifugation. Different phenotypes of human monocyte-derived macrophages (MDM) were used to study the anti-inflammatory properties of EV in vitro, and the medial meniscectomy-induced rat model of knee osteoarthritis (MMx) was used in vivo. The study found that both EV reduced pro-inflammatory cytokines IL-6 and TNF-α in MDM. However, exosomes showed superior results, preserving the extracellular matrix (ECM) of hyaline cartilage, and reducing synovitis more effectively than MBVs. Additionally, exosomes downregulated inflammatory markers (TNF-α, iNOS) and increased Arg-1 expression in macrophages and synovial fibroblasts, indicating a stronger anti-inflammatory effect. These results suggest UC-MSC exosomes as a promising therapeutic option for OA, with the potential for modulating inflammation and promoting joint tissue regeneration. Full article
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