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Life
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The Therapeutic Applications of Extracellular Vesicles
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The Therapeutic Applications of Extracellular Vesicles

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (17 March 2023) | Viewed by 20040

Special Issue Editor

Prof. Dr. Yong Weon Yi

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Guest Editor
Department of Biochemistry, Dankook University College of Medicine, Cheonan 31116, Republic of Korea
Interests: protein kinases; small molecule inhibitors; anticancer therapeutics; drug repositioning; synthetic lethal; triple-negative breast cancer; exosomes; extracellular vesicles

Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs) collectively refer microvesicles, exosomes, apoptotic bodies, and other vesicular entities secreted by living cells. Now, it has been well established that EVs have important roles in exchanging information from cell to cell and regulating cellular physiology in both healthy and disease conditions. In addition, EVs themselves are appreciated as a potential therapeutic and drug delivery vehicle with compatible tolerance and excellent delivery efficacy. EVs are also a potential therapeutic targets to treating intractable diseases such as cancers. Serum EVs have been also investigated as a diagnostic markers. EVs from diverse sources are being studied for therapeutics in vitro and in vivo. However, many barriers are still out there. Standard methods for EV production and measurements need to be further improved as chemistry manufacturing and control (CMC) to obtain pharmaceutical grade EVs. Consensus definition of EV dose is also required to compare EVs from diverse sources and/or manufacturing methods for preclinical and later clinical studies.

The Special Issue on “The therapeutic applications of extracellular vesicles” is intended to provide a unique international forum covering a broad description of results providing the current advancement on the development of EVs as therapeutics. Scientists working on EVs produced from many diverse sources and methods for therapeutic applications are invited to contribute their data and insights on methodologies that enhanced the progress of therapeutic EV development.

Dr. Yong Weon Yi
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. Life 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
  • regenerative medicine
  • drug delivery
  • manufacturing standards
  • GMP manufacturing
  • CMC

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Published Papers (7 papers)

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Editorial

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4 pages, 205 KiB  
Editorial
Extracellular Vesicles as a New Therapeutic Entity
by Yong Weon Yi
Life 2023, 13(6), 1235; https://doi.org/10.3390/life13061235 - 24 May 2023
Viewed by 1287
Abstract
Collectively, extracellular vesicles (EVs) refer to vesicular entities secreted by live cells, including microvesicles, exosomes, and apoptotic bodies [...] Full article
(This article belongs to the Special Issue The Therapeutic Applications of Extracellular Vesicles)

Research

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17 pages, 2094 KiB  
Article
Characterization and microRNA Expression Analysis of Serum-Derived Extracellular Vesicles in Severe Liver Injury from Chronic HBV Infection
by Min Liu, Xionghao Liu, Mengmeng Pan, Yu Zhang, Xiangling Tang, Wanxi Liu, Mingri Zhao, Jing Ma, Ning Zhou, Yongfang Jiang, Wenlong Wang and Mujun Liu
Life 2023, 13(2), 347; https://doi.org/10.3390/life13020347 - 28 Jan 2023
Cited by 5 | Viewed by 1978
Abstract
Background: Extracellular vesicle (EV) microRNAs have been documented in several studies to have significantly different expressions in hepatitis B virus (HBV)-related liver diseases, such as hepatocellular carcinoma (HCC). The current work aimed to observe the characteristics of EVs and EV miRNA expressions in [...] Read more.
Background: Extracellular vesicle (EV) microRNAs have been documented in several studies to have significantly different expressions in hepatitis B virus (HBV)-related liver diseases, such as hepatocellular carcinoma (HCC). The current work aimed to observe the characteristics of EVs and EV miRNA expressions in patients with severe liver injury chronic hepatitis B (CHB) and patients with HBV-associated decompensated cirrhosis (DeCi). Methods: The characterization of the EVs in the serum was carried out for three different groups, namely, patients with severe liver injury-CHB, patients with DeCi, and healthy controls. EV miRNAs were analyzed using miRNA-seq and RT-qPCR arrays. Additionally, we assessed the predictive and observational values of the miRNAs with significant differential expressions in serum EVs. Results: Patients with severe liver injury-CHB had the highest EV concentrations when compared to the normal controls (NCs) and patients with DeCi (p < 0.001). The miRNA-seq of the NC and severe liver injury-CHB groups identified 268 differentially expressed miRNAs (|FC| > 2, p < 0.05). In this case, 15 miRNAs were verified using RT-qPCR, and it was found that novel-miR-172-5p and miR-1285-5p in the severe liver injury-CHB group showed marked downregulation in comparison to the NC group (p < 0.001). Furthermore, compared with the NC group, three EV miRNAs (novel-miR-172-5p, miR-1285-5p, and miR-335-5p) in the DeCi group showed various degrees of downregulated expression. However, when comparing the DeCi group with the severe liver injury-CHB group, only the expression of miR-335-5p in the DeCi group decreased significantly (p < 0.05). For the severe liver injury-CHB and DeCi groups, the addition of miR-335-5p improved the predictive accuracy of the serological levels, while miR-335-5p was significantly correlated with ALT, AST, AST/ALT, GGT, and AFP. Conclusions: The patients with severe liver injury-CHB had the highest number of EVs. The combination of novel-miR-172-5p and miR-1285-5p in serum EVs helped in predicting the progression of the NCs to severe liver injury-CHB, while the addition of EV miR-335-5p improved the serological accuracy of predicting the progression of severe liver injury-CHB to DeCi. Full article
(This article belongs to the Special Issue The Therapeutic Applications of Extracellular Vesicles)
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20 pages, 7884 KiB  
Article
Combination Therapy Comprising Paclitaxel and 5-Fluorouracil by Using Folic Acid Functionalized Bovine Milk Exosomes Improves the Therapeutic Efficacy against Breast Cancer
by Dulla Naveen Kumar, Aiswarya Chaudhuri, Deepa Dehari, Anusmita Shekher, Subash C. Gupta, Shreyasi Majumdar, Sairam Krishnamurthy, Sanjay Singh, Dinesh Kumar and Ashish Kumar Agrawal
Life 2022, 12(8), 1143; https://doi.org/10.3390/life12081143 - 28 Jul 2022
Cited by 46 | Viewed by 4114
Abstract
Paclitaxel (PAC) has been approved by FDA for clinical use (Taxol®), yet dose-dependent severe toxicity due to the adjuvant Cremophor EL® in combination with ethanol is a major drawback. The drawbacks of the current therapy can be overcome by (i) [...] Read more.
Paclitaxel (PAC) has been approved by FDA for clinical use (Taxol®), yet dose-dependent severe toxicity due to the adjuvant Cremophor EL® in combination with ethanol is a major drawback. The drawbacks of the current therapy can be overcome by (i) finding a suitable vehicle that cannot only bypass the above adjuvant but also be used to deliver drugs orally and (ii) combining the PAC with some other chemotherapeutics to have the enhanced therapeutic efficacy. In the current work, we have used folic acid (FA) functionalized bovine milk-derived exosomes for oral delivery of PAC in combination with 5-fluorouracil (5-FU). Exosomes before and after the drug loading were found to have a particle size in the range of 80–100 nm, polydispersity index (PDI ~0.20), zeta potential (~−25 mV), entrapment efficiency (~82%), practical drug loading (~28%) and sustained drug release for 48 h. Significant decreases in IC50 were observed in the case of exosomes loaded drugs which further improved following the FA functionalization. FA functionalized coumarin-6-loaded exosomes showed remarkably higher cellular uptake in comparison with free coumarin-6. Moreover, FA-functionalized drug-loaded exosomes showed a higher apoptotic index with better control over cell migration. Collectively, data suggested the enhanced efficacy of the combination following its loading to the folic acid functionalized exosomes against breast cancer. Full article
(This article belongs to the Special Issue The Therapeutic Applications of Extracellular Vesicles)
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10 pages, 1721 KiB  
Article
Mesenchymal-Stem-Cell-Derived Extracellular Vesicles Attenuate Brain Injury in Escherichia coli Meningitis in Newborn Rats
by Young-Eun Kim, So-Yoon Ahn, Won-Soon Park, Dong-Kyung Sung, Se-In Sung, Mi-Sun Yang and Yun-Sil Chang
Life 2022, 12(7), 1030; https://doi.org/10.3390/life12071030 - 11 Jul 2022
Cited by 6 | Viewed by 2197
Abstract
We recently reported that transplantation of mesenchymal stem cells (MSCs) significantly reduced bacterial growth and brain injury in neonatal meningitis induced by Escherichia coli (E. coli) infection in newborn rats. As a next step, to verify whether the MSCs protect against [...] Read more.
We recently reported that transplantation of mesenchymal stem cells (MSCs) significantly reduced bacterial growth and brain injury in neonatal meningitis induced by Escherichia coli (E. coli) infection in newborn rats. As a next step, to verify whether the MSCs protect against brain injury in a paracrine manner, this study was designed to estimate the efficacy of MSC-derived extracellular vesicles (MSC-EVs) in E. coli meningitis in newborn rats. E. coli meningitis was induced without concomitant bacteremia by the intra-cerebroventricular injection of 5 × 102 colony-forming units of K1 (-) E. coli in rats, at postnatal day 11. MSC-EVs were intra-cerebroventricularly transplanted 6 h after the induction of meningitis, and antibiotics were administered for three consecutive days starting at 24 h after the induction of meningitis. The increase in bacterial growth in the cerebrospinal fluid measured at 24 h after the meningitis induction was not significantly reduced following MSC-EV transplantation. However, an increase in brain cell death, reactive gliosis, and inflammation following meningitis were significantly attenuated after MSC-EV transplantation. Taken together, our results indicate that MSCs show anti-apoptotic, anti-gliosis, and anti-inflammatory, but not antibacterial effects, in an EV-mediated paracrine manner in E. coli-induced neonatal meningitis. Full article
(This article belongs to the Special Issue The Therapeutic Applications of Extracellular Vesicles)
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Review

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14 pages, 1301 KiB  
Review
Shedding Lights on the Extracellular Vesicles as Functional Mediator and Therapeutic Decoy for COVID-19
by Abhimanyu Thakur
Life 2023, 13(3), 840; https://doi.org/10.3390/life13030840 - 20 Mar 2023
Cited by 4 | Viewed by 2540
Abstract
COVID-19 is an infectious disease caused by the novel coronavirus (SARS-CoV-2) that first appeared in late 2019 and has since spread across the world. It is characterized by symptoms such as fever, cough, and shortness of breath and can lead to death in [...] Read more.
COVID-19 is an infectious disease caused by the novel coronavirus (SARS-CoV-2) that first appeared in late 2019 and has since spread across the world. It is characterized by symptoms such as fever, cough, and shortness of breath and can lead to death in severe cases. To help contain the virus, measures such as social distancing, handwashing, and other public health measures have been implemented. Vaccine and drug candidates, such as those developed by Pfizer/BioNTech, AstraZeneca, Moderna, Novavax, and Johnson & Johnson, have been developed and are being distributed worldwide. Clinical trials for drug treatments such as remdesivir, dexamethasone, and monoclonal antibodies are underway and have shown promising results. Recently, exosomes have gained attention as a possible mediator of the COVID-19 infection. Exosomes, small vesicles with a size of around 30–200 nm, released from cells, contain viral particles and other molecules that can activate the immune system and/or facilitate viral entry into target cells. Apparently, the role of exosomes in eliciting various immune responses and causing tissue injury in COVID-19 pathogenesis has been discussed. In addition, the potential of exosomes as theranostic and therapeutic agents for the treatment of COVID-19 has been elaborated. Full article
(This article belongs to the Special Issue The Therapeutic Applications of Extracellular Vesicles)
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24 pages, 731 KiB  
Review
EVs-miRNA: The New Molecular Markers for Chronic Respiratory Diseases
by Piera Soccio, Giorgia Moriondo, Donato Lacedonia, Pasquale Tondo, Carla Maria Irene Quarato, Maria Pia Foschino Barbaro and Giulia Scioscia
Life 2022, 12(10), 1544; https://doi.org/10.3390/life12101544 - 5 Oct 2022
Cited by 15 | Viewed by 2869
Abstract
Idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), asthma and sleep disorders are chronic respiratory diseases that affect the airways, compromising lung function over time. These diseases affect hundreds of millions of people around the world and their frequency seems to be [...] Read more.
Idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), asthma and sleep disorders are chronic respiratory diseases that affect the airways, compromising lung function over time. These diseases affect hundreds of millions of people around the world and their frequency seems to be increasing every year. Extracellular vesicles (EVs) are small-sized vesicles released by every cell in the body. They are present in most body fluids and contain various biomolecules including proteins, lipids, mRNA and non-coding RNA (micro-RNA). The EVs can release their cargo, specifically micro-RNAs (miRNAs), to both neighboring and/or distal cells, playing a fundamental role in cell–cell communication. Recent studies have shown their possible role in the pathogenesis of various chronic respiratory diseases. The expression of miRNAs and, in particular, of miRNAs contained within the extracellular vesicles seems to be a good starting point in order to identify new potential biomarkers of disease, allowing a non-invasive clinical diagnosis. In this review we summarize some studies, present in the literature, about the functions of extracellular vesicles and miRNAs contained in extracellular vesicles in chronic respiratory diseases and we discuss the potential clinical applications of EVs and EVs-miRNAs for their possible use such as future biomarkers. Full article
(This article belongs to the Special Issue The Therapeutic Applications of Extracellular Vesicles)
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13 pages, 1382 KiB  
Review
3D Spheroid Cultures of Stem Cells and Exosome Applications for Cartilage Repair
by Seung Yeon Lee and Jin Woo Lee
Life 2022, 12(7), 939; https://doi.org/10.3390/life12070939 - 22 Jun 2022
Cited by 16 | Viewed by 4106
Abstract
Cartilage is a connective tissue that constitutes the structure of the body and consists of chondrocytes that produce considerable collagenous extracellular matrix and plentiful ground substances, such as proteoglycan and elastin fibers. Self-repair is difficult when the cartilage is damaged because of insufficient [...] Read more.
Cartilage is a connective tissue that constitutes the structure of the body and consists of chondrocytes that produce considerable collagenous extracellular matrix and plentiful ground substances, such as proteoglycan and elastin fibers. Self-repair is difficult when the cartilage is damaged because of insufficient blood supply, low cellularity, and limited progenitor cell numbers. Therefore, three-dimensional (3D) culture systems, including pellet culture, hanging droplets, liquid overlays, self-injury, and spinner culture, have attracted attention. In particular, 3D spheroid culture strategies can enhance the yield of exosome production of mesenchymal stem cells (MSCs) when compared to two-dimensional culture, and can improve cellular restorative function by enhancing the paracrine effects of MSCs. Exosomes are membrane-bound extracellular vesicles, which are intercellular communication systems that carry RNAs and proteins. Information transfer affects the phenotype of recipient cells. MSC-derived exosomes can facilitate cartilage repair by promoting chondrogenic differentiation and proliferation. In this article, we reviewed recent major advances in the application of 3D culture techniques, cartilage regeneration with stem cells using 3D spheroid culture system, the effect of exosomes on chondrogenic differentiation, and chondrogenic-specific markers related to stem cell derived exosomes. Furthermore, the utilization of MSC-derived exosomes to enhance chondrogenic differentiation for osteoarthritis is discussed. If more mechanistic studies at the molecular level are conducted, MSC-spheroid-derived exosomes will supply a better therapeutic option to improve osteoarthritis. Full article
(This article belongs to the Special Issue The Therapeutic Applications of Extracellular Vesicles)
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