Submit to Special Issue Submit Abstract to Special Issue Review for Biomedicines Propose a Special Issue

Journal Browser

Extracellular Vesicles and Exosomes as Therapeutic Agents

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 31 October 2024 | Viewed by 11564

Share This Special Issue

Special Issue Editor

Dr. David J. Rademacher

E-Mail Website
Guest Editor

Stritch School of Medicine, Core Microscopy Facility and Department of Microbiology and Immunology, Loyola University Chicago, Chicago, IL USA
Interests: neurodegenerative disease; addiction; microscopy; senescence; therapeutics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs) are lipid-bound vesicles secreted by cells into the extracellular space. The three main subtypes of EVs—microvesicles, exosomes, and apoptotic bodies—are differentiated based on their biogenesis, release pathway, size, content, and function. The content or “cargo” of EVs include nucleic acids, lipids, proteins, and metabolites. The role of EVs in cell–cell communication and their ability to act as carriers of biomarkers for diseases are well-established. EVs are widely considered as promising therapeutic options because they have a long circulating half-life, are tolerated well by the human body, are capable of penetrating cell membranes and targeting specific cell types, and have the capacity to be engineered. Indeed, the use of EVs (predominantly exosomes) as therapeutic agents and/or drug-delivery systems in neurodegenerative diseases, cancers, stroke, myocardial infarction, and several other pathologies has been the subject of intense research. Despite recent advances, a better understanding of the mechanisms by which EVs function would help unlock the full potential of EV-based therapeutics. This Special Issue welcomes articles focused on the use of EVs—including exosomes—as therapeutic agents, with a focus on articles that provide a better understanding of the uptake, biodistribution, and trafficking of EVs or elucidate the mechanisms by which EVs exert their therapeutic effects.

Dr. David J. Rademacher
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

extracellular vesicles
exosomes
therapeutics
drug delivery
bioengineering

Published Papers (7 papers)

Download All Papers

Research

Jump to: Review

16 pages, 6155 KiB

Open AccessArticle

Artificial Extracellular Vesicles Generated from T Cells Using Different Induction Techniques

by Ekaterina A. Zmievskaya, Sabir A. Mukhametshin, Irina A. Ganeeva, Elvina M. Gilyazova, Elvira T. Siraeva, Marianna P. Kutyreva, Artur A. Khannanov, Youyong Yuan and Emil R. Bulatov

Biomedicines 2024, 12(4), 919; https://doi.org/10.3390/biomedicines12040919 - 20 Apr 2024

Viewed by 573

Abstract

Cell therapy is at the forefront of biomedicine in oncology and regenerative medicine. However, there are still significant challenges to their wider clinical application such as limited efficacy, side effects, and logistical difficulties. One of the potential approaches that could overcome these problems is based on extracellular vesicles (EVs) as a cell-free therapy modality. One of the major obstacles in the translation of EVs into practice is their low yield of production, which is insufficient to achieve therapeutic amounts. Here, we evaluated two primary approaches of artificial vesicle induction in primary T cells and the SupT1 cell line—cytochalasin B as a chemical inducer and ultrasonication as a physical inducer. We found that both methods are capable of producing artificial vesicles, but cytochalasin B induction leads to vesicle yield compared to natural secretion, while ultrasonication leads to a three-fold increase in particle yield. Cytochalasin B induces the formation of vesicles full of cytoplasmic compartments without nuclear fraction, while ultrasonication induces the formation of particles rich in membranes and membrane-related components such as CD3 or HLAII proteins. The most effective approach for T-cell induction in terms of the number of vesicles seems to be the combination of anti-CD3/CD28 antibody activation with ultrasonication, which leads to a seven-fold yield increase in particles with a high content of functionally important proteins (CD3, granzyme B, and HLA II). Full article

(This article belongs to the Special Issue Extracellular Vesicles and Exosomes as Therapeutic Agents)

► Show Figures

Figure 1

28 pages, 6431 KiB

Open AccessArticle

Extracellular Vesicles Derived from Osteogenic-Differentiated Human Bone Marrow-Derived Mesenchymal Cells Rescue Osteogenic Ability of Bone Marrow-Derived Mesenchymal Cells Impaired by Hypoxia

by Chenglong Wang, Sabine Stöckl, Girish Pattappa, Daniela Schulz, Korbinian Hofmann, Jovana Ilic, Yvonne Reinders, Richard J. Bauer, Albert Sickmann and Susanne Grässel

Biomedicines 2023, 11(10), 2804; https://doi.org/10.3390/biomedicines11102804 - 16 Oct 2023

Viewed by 1059

Abstract

In orthopedics, musculoskeletal disorders, i.e., non-union of bone fractures or osteoporosis, can have common histories and symptoms related to pathological hypoxic conditions induced by aging, trauma or metabolic disorders. Here, we observed that hypoxic conditions (2% O₂) suppressed the osteogenic differentiation of human bone marrow-derived mesenchymal cells (hBMSC) in vitro and simultaneously increased reactive oxygen species (ROS) production. We assumed that cellular origin and cargo of extracellular vesicles (EVs) affect the osteogenic differentiation capacity of hBMSCs cultured under different oxygen pressures. Proteomic analysis revealed that EVs isolated from osteogenic differentiated hBMSC cultured under hypoxia (hypo-osteo EVs) or under normoxia (norm-osteo EVs) contained distinct protein profiles. Extracellular matrix (ECM) components, antioxidants and pro-osteogenic proteins were decreased in hypo-osteo EVs. The proteomic analysis in our previous study revealed that under normoxic culture conditions, pro-osteogenic proteins and ECM components have higher concentrations in norm-osteo EVs than in EVs derived from naïve hBMSCs (norm-naïve EVs). When selected for further analysis, five anti-hypoxic proteins were significantly upregulated (response to hypoxia) in norm-osteo EVs. Three of them are characterized as antioxidant proteins. We performed qRT-PCR to verify the corresponding gene expression levels in the norm-osteo EVs’ and norm-naïve EVs’ parent cells cultured under normoxia. Moreover, we observed that norm-osteo EVs rescued the osteogenic ability of naïve hBMSCs cultured under hypoxia and reduced hypoxia-induced elevation of ROS production in osteogenic differentiated hBMSCs, presumably by inducing expression of anti-hypoxic/ antioxidant and pro-osteogenic genes. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Exosomes as Therapeutic Agents)

► Show Figures

Figure 1

14 pages, 3348 KiB

Open AccessArticle

The Influence of Exercise-Associated Small Extracellular Vesicles on Trophoblasts In Vitro

by Shuhiba Mohammad, Jayonta Bhattacharjee, Velislava Tzaneva, Kelly Ann Hutchinson, Madeeha Shaikh, Danilo Fernandes da Silva, Dylan Burger and Kristi B. Adamo

Biomedicines 2023, 11(3), 857; https://doi.org/10.3390/biomedicines11030857 - 11 Mar 2023

Viewed by 1627

Abstract

Exercise induces the release of small extracellular vesicles (sEVs) into circulation that are postulated to mediate tissue cross-talk during exercise. We previously reported that pregnant individuals released greater levels of sEVs into circulation after exercise compared to matched non-pregnant controls, but their biological functions remain unknown. In this study, sEVs isolated from the plasma of healthy pregnant and non-pregnant participants after a single bout of moderate-intensity exercise were evaluated for their impact on trophoblasts in vitro. Exercise-associated sEVs were found localized within the cytoplasm of BeWo choriocarcinoma cells, used to model trophoblasts in vitro. Exposure to exercise-associated sEVs did not significantly alter BeWo cell proliferation, gene expression of angiogenic growth factors VEGF and PLGF, or the release of the hormone human chorionic gonadotropin. The results from this pilot study support that exercise-associated sEVs could interact with trophoblasts in vitro, and warrant further investigation to reveal their potential role in communicating the effects of exercise to the maternal–fetal interface. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Exosomes as Therapeutic Agents)

► Show Figures

Figure 1

14 pages, 1082 KiB

Open AccessArticle

Antimicrobial and Immunomodulatory Potential of Cow Colostrum Extracellular Vesicles (ColosEVs) in an Intestinal In Vitro Model

by Samanta Mecocci, Livia De Paolis, Roberto Zoccola, Floriana Fruscione, Chiara Grazia De Ciucis, Elisabetta Chiaradia, Valentina Moccia, Alessia Tognoloni, Luisa Pascucci, Simona Zoppi, Valentina Zappulli, Giovanni Chillemi, Maria Goria, Katia Cappelli and Elisabetta Razzuoli

Biomedicines 2022, 10(12), 3264; https://doi.org/10.3390/biomedicines10123264 - 15 Dec 2022

Cited by 1 | Viewed by 1778

Abstract

Extracellular Vesicles (EVs) are nano-sized double-lipid-membrane-bound structures, acting mainly as signalling mediators between distant cells and, in particular, modulating the immune response and inflammation of targeted cells. Milk and colostrum contain high amounts of EVs that could be exploited as alternative natural systems in antimicrobial fighting. The aim of this study is to evaluate cow colostrum-derived EVs (colosEVs) for their antimicrobial, anti-inflammatory and immunomodulating effects in vitro to assess their suitability as natural antimicrobial agents as a strategy to cope with the drug resistance problem. ColosEVs were evaluated on a model of neonatal calf diarrhoea caused by Escherichia coli infection, a livestock disease where antibiotic therapy often has poor results. Colostrum from Piedmontese cows was collected within 24 h of calving and colosEVs were immediately isolated. IPEC-J2 cell line was pre-treated with colosEVs for 48 h and then infected with EPEC/NTEC field strains for 2 h. Bacterial adherence and IPEC-J2 gene expression analysis (RT-qPCR) of CXCL8, DEFB1, DEFB4A, TLR4, TLR5, NFKB1, MYD88, CGAS, RIGI and STING were evaluated. The colosEVs pre-treatment significantly reduced the ability of EPEC/NTEC strains to adhere to cell surfaces (p = 0.006), suggesting a role of ColosEVs in modulating host–pathogen interactions. Moreover, our results showed a significant decrease in TLR5 (p < 0.05), CGAS (p < 0.05) and STING (p < 0.01) gene expression in cells that were pre-treated with ColosEVs and then infected, thus highlighting a potential antimicrobial activity of ColosEVs. This is the first preliminarily study investigating ColosEV immunomodulatory and anti-inflammatory effects on an in vitro model of neonatal calf diarrhoea, showing its potential as a therapeutic and prophylactic tool. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Exosomes as Therapeutic Agents)

► Show Figures

Figure 1

Review

Jump to: Research

37 pages, 2081 KiB

Open AccessReview

Effects of Physical Cues on Stem Cell-Derived Extracellular Vesicles toward Neuropathy Applications

by Danyale Berry, Justice Ene, Aakash Nathani, Mandip Singh, Yan Li and Changchun Zeng

Biomedicines 2024, 12(3), 489; https://doi.org/10.3390/biomedicines12030489 - 22 Feb 2024

Viewed by 887

Abstract

The peripheral nervous system undergoes sufficient stress when affected by diabetic conditions, chemotherapeutic drugs, and personal injury. Consequently, peripheral neuropathy arises as the most common complication, leading to debilitating symptoms that significantly alter the quality and way of life. The resulting chronic pain requires a treatment approach that does not simply mask the accompanying symptoms but provides the necessary external environment and neurotrophic factors that will effectively facilitate nerve regeneration. Under normal conditions, the peripheral nervous system self-regenerates very slowly. The rate of progression is further hindered by the development of fibrosis and scar tissue formation, which does not allow sufficient neurite outgrowth to the target site. By incorporating scaffolding supplemented with secretome derived from human mesenchymal stem cells, it is hypothesized that neurotrophic factors and cellular signaling can facilitate the optimal microenvironment for nerve reinnervation. However, conventional methods of secretory vesicle production are low yield, thus requiring improved methods to enhance paracrine secretions. This report highlights the state-of-the-art methods of neuropathy treatment as well as methods to optimize the clinical application of stem cells and derived secretory vesicles for nerve regeneration. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Exosomes as Therapeutic Agents)

► Show Figures

Figure 1

19 pages, 1275 KiB

Open AccessReview

Potential for Therapeutic-Loaded Exosomes to Ameliorate the Pathogenic Effects of α-Synuclein in Parkinson’s Disease

by David J. Rademacher

Biomedicines 2023, 11(4), 1187; https://doi.org/10.3390/biomedicines11041187 - 17 Apr 2023

Cited by 5 | Viewed by 2004

Abstract

Pathogenic forms of α-synuclein (α-syn) are transferred to and from neurons, astrocytes, and microglia, which spread α-syn pathology in the olfactory bulb and the gut and then throughout the Parkinson’s disease (PD) brain and exacerbate neurodegenerative processes. Here, we review attempts to minimize or ameliorate the pathogenic effects of α-syn or deliver therapeutic cargo into the brain. Exosomes (EXs) have several important advantages as carriers of therapeutic agents including an ability to readily cross the blood–brain barrier, the potential for targeted delivery of therapeutic agents, and immune resistance. Diverse cargo can be loaded via various methods, which are reviewed herein, into EXs and delivered into the brain. Genetic modification of EX-producing cells or EXs and chemical modification of EX have emerged as powerful approaches for the targeted delivery of therapeutic agents to treat PD. Thus, EXs hold great promise for the development of next-generation therapeutics for the treatment of PD. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Exosomes as Therapeutic Agents)

► Show Figures

Figure 1

24 pages, 1822 KiB

Open AccessReview

Regenerative Effects of Exosomes-Derived MSCs: An Overview on Spinal Cord Injury Experimental Studies

by Giovanni Schepici, Serena Silvestro and Emanuela Mazzon

Biomedicines 2023, 11(1), 201; https://doi.org/10.3390/biomedicines11010201 - 13 Jan 2023

Cited by 5 | Viewed by 2095

Abstract

Spinal cord injury (SCI) is a devastating condition usually induced by the initial mechanical insult that can lead to permanent motor and sensory deficits. At present, researchers are investigating potential therapeutic strategies to ameliorate the neuro-inflammatory cascade that occurs post-injury. Although the use of mesenchymal stromal/stem (MSCs) as a potential therapy in application to regenerative medicine promoted anti-inflammatory and neuroprotective effects, several disadvantages limit their use. Therefore, recent studies have reported the effects of exosomes-derived MSCs (MSC-EXOs) as an innovative therapeutic option for SCI patients. It is noteworthy that MSC-EXOs can maintain the integrity of the blood-spinal cord barrier (BSCB), promoting angiogenic, proliferative, and anti-oxidant effects, as well as immunomodulatory, anti-inflammatory, and antiapoptotic properties. Therefore, in this study, we summarized the preclinical studies reported in the literature that have shown the effects of MSC-EXOs as a new molecular target to counteract the devastating effects of SCI. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Exosomes as Therapeutic Agents)

► Show Figures