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Life
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Exosomes: Biogenesis, Biologic Function and Clinical Potential
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Exosomes: Biogenesis, Biologic Function and Clinical Potential

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Cell Biology and Tissue Engineering".

Deadline for manuscript submissions: closed (18 November 2022) | Viewed by 33894

Special Issue Editors

Dr. Lara Console

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Guest Editor
Department DiBEST (Biologia, Ecologia, Scienze della Terra), University of Calabria, Via P. Bucci 4c, 87036 Arcavacata di Rende (CS), Italy
Interests: carnitine transporters; exosomes; post-translational modifications
Special Issues, Collections and Topics in MDPI journals
Dr. Mariafrancesca Scalise

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Guest Editor
Department DiBEST (Biologia, Ecologia, Scienze della Terra), University of Calabria, Via P. Bucci 4c, 87036 Arcavacata di Rende (CS), Italy
Interests: proteoliposome; membrane transporters; plasma membrane; protein purification; amino acids; cancer cell line; exosomes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is our pleasure to announce the launch of a new Special Issue in Life on the highly relevant topic of "Exosomes: Biogenesis, Biological Function, and Clinical Potential”.

Exosomes are a subtype of extracellular vesicles that can be identified based on their endosomal origin and their size, which ranges from 40 to 160 nm. Exosomes have been reported in all biological fluids, and their composition reflects the metabolic state of the cell of origin. Their physiological function is linked to intercellular communication and organ homeostasis. However, a large body of proof links exosomes with several pathologies, including cardiovascular diseases, cancer progression, chronic inflammation, renal diseases, neurodegenerative diseases, and metabolic diseases.

Therefore, exosome components, including nucleic acids, proteins, lipids, amino acids, and metabolites, represent sources of new potential biomarkers for the follow-up of disease progression and response to therapies. Moreover, the multicomponent analysis of exosomes may represent a non-invasive method for diagnosis and prognosis determination; indeed, exosomes are readily accessible via sampling of biological fluids (liquid biopsies).

Moreover, exosomes are also promising therapeutic vehicles for drug and gene delivery. Indeed, upon release from cells of origin, exosomes can be selectively taken up by both neighbor and distant target cells and have the ability to reprogram the metabolism of these recipient cells. Due to their lipid and cell surface protein composition, engineered exosomes pre-loaded with therapeutic agents may improve pharmacokinetics and bioavailability and minimize adverse reactions.

Despite recent progress in studies of biogenesis, molecular composition, and isolation technologies of exosomes, further investigations are needed to make exosomes valuable diagnostic/prognostic biomarkers and reliable vehicles for therapeutics delivery.

This Special Issue aims to furnish an update on the physiopathological function and clinical application of exosomes. We welcome submissions of original research papers and reviews from different disciplines, including biochemistry, molecular biology, cell biology, genetics, medical sciences, and biotechnology.

Dr. Lara Console
Dr. Mariafrancesca Scalise
Guest Editors

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

  • exosomes
  • biomarkers
  • clinical potential of exosomes
  • therapeutic vehicles

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Published Papers (9 papers)

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Research

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13 pages, 2284 KiB  
Article
Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Alleviate Ischemia-Reperfusion Injury and Promote Survival of Skin Flaps in Rats
by Qifang Niu, Yang Yang, Delong Li, Wenwen Guo, Chong Wang, Haoyue Xu, Zhien Feng and Zhengxue Han
Life 2022, 12(10), 1567; https://doi.org/10.3390/life12101567 - 9 Oct 2022
Cited by 17 | Viewed by 2405
Abstract
Free tissue flap transplantation is a classic and important method for the clinical repair of tissue defects. However, ischemia-reperfusion (IR) injury can affect the success rate of skin flap transplantation. We used a free abdomen flap rat model to explore the protective effects [...] Read more.
Free tissue flap transplantation is a classic and important method for the clinical repair of tissue defects. However, ischemia-reperfusion (IR) injury can affect the success rate of skin flap transplantation. We used a free abdomen flap rat model to explore the protective effects of exosomes derived from bone marrow mesenchymal stem cells (BMSCs-exosomes) against the IR injury of the skin flap. Exosomes were injected through the tail vein and the flaps were observed and obtained on day 7. We observed that BMSCs-exosomes significantly reduced the necrotic lesions of the skin flap. Furthermore, BMSCs-exosomes relieved oxidative stress and reduced the levels of inflammatory factors. Apoptosis was evaluated via the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and Western blot analysis of Bax, Bcl-2. Simultaneously, BMSCs-exosomes promoted the formation of new blood vessels in the IR flap, as confirmed by the increased expression level of VEGFA and the fluorescence co-staining of CD31 and PCNA. Additionally, BMSCs-exosomes considerably increased proliferation and migration of human umbilical vein endothelial cells and promoted angiogenesis in vitro. BMSCs-exosomes could be a promising cell-free therapeutic candidate to reduce IR injury and promote the survival of skin flaps. Full article
(This article belongs to the Special Issue Exosomes: Biogenesis, Biologic Function and Clinical Potential)
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17 pages, 4102 KiB  
Article
Gallic Acid Ameliorates the Inflammatory State of Periodontal Ligament Stem Cells and Promotes Pro-Osteodifferentiation Capabilities of Inflammatory Stem Cell-Derived Exosomes
by Zhenning Dai, Ziyue Li, Weihan Zheng, Zi Yan, Lijun Zhang, Jiaxin Yang, Jing Xiao, Hanxiao Sun, Shiyu Li and Wenhua Huang
Life 2022, 12(9), 1392; https://doi.org/10.3390/life12091392 - 6 Sep 2022
Cited by 9 | Viewed by 2475
Abstract
The slow proliferation rate and poor osteodifferentiation ability of inflammatory periodontal membrane stem cells extracted from periodontitis tissues (i-PDLSCs) account for poor efficiency in treating inflammatory bone loss. Exosomes reportedly have inducible and relatively stable components, allowing them to promote inflammatory bone repair, [...] Read more.
The slow proliferation rate and poor osteodifferentiation ability of inflammatory periodontal membrane stem cells extracted from periodontitis tissues (i-PDLSCs) account for poor efficiency in treating inflammatory bone loss. Exosomes reportedly have inducible and relatively stable components, allowing them to promote inflammatory bone repair, but obtaining i-PDLSCs exosomes with the ability to promote osteodifferentiation is challenging. In the present study, i-PDLSCs were extracted from periodontal membrane tissues of patients with severe periodontitis, and in vitro induction with gallic acid (GA) significantly promoted the proliferative activity of i-PDLSCs at a concentration of 10 mM, with TC0 of 11.057 mM and TC50 of 67.56 mM for i-PDLSCs. After mRNA sequencing, we found that GA could alleviate oxidative stress in i-PDLSCs and increase its mitochondrial membrane potential and glucose aerobic metabolism level, thus promoting the osteodifferentiation of i-PDLSCs. After exosomes of i-PDLSCs after GA induction (i-EXO-GA) were isolated by differential centrifugation, we found that 200 ug/mL of i-EXO-GA could remarkably promote the osteodifferentiation of i-PDLSCs. Overall, our results suggest that GA induction can enhance the proliferation and osteodifferentiation in primary cultures of i-PDLSCs in vitro, mediated by alleviating oxidative stress and glycometabolism levels in cells, which further influences the osteodifferentiation-promoting ability of i-EXO-GA. Overall, we provide a viable cell and exosome induction culture method for treating inflammatory alveolar defects associated with periodontitis. Full article
(This article belongs to the Special Issue Exosomes: Biogenesis, Biologic Function and Clinical Potential)
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22 pages, 8927 KiB  
Article
Bone Marrow Mesenchymal Stem Cells and Their Derived Extracellular Vesicles Attenuate Non-Alcoholic Steatohepatitis-Induced Cardiotoxicity via Modulating Cardiac Mechanisms
by Marwa O. El-Derany and Sherihan G. AbdelHamid
Life 2022, 12(3), 355; https://doi.org/10.3390/life12030355 - 28 Feb 2022
Cited by 2 | Viewed by 3201
Abstract
Cardiovascular-disease (CVD)-related mortality has been fueled by the upsurge of non-alcoholic steatohepatitis (NASH). Mesenchymal stem cells (MSCs) were extensively studied for their reparative power in ameliorating different CVDs via direct and paracrine effects. Several reports pointed to the importance of bone marrow mesenchymal [...] Read more.
Cardiovascular-disease (CVD)-related mortality has been fueled by the upsurge of non-alcoholic steatohepatitis (NASH). Mesenchymal stem cells (MSCs) were extensively studied for their reparative power in ameliorating different CVDs via direct and paracrine effects. Several reports pointed to the importance of bone marrow mesenchymal stem cells (BM-MSCs) as a reliable therapeutic approach for several CVDs. Nevertheless, their therapeutic potential has not yet been investigated in the cardiotoxic state that is induced by NASH. Thus, this study sought to investigate the molecular mechanisms associated with cardiotoxicity that accompany NASH. Besides, we aimed to comparatively study the therapeutic effects of bone-marrow mesenchymal-stem-cell-derived extracellular vesicles (BM-MSCs-EV) and BM-MSCs in a cardiotoxic model that is induced by NASH in rats. Rats were fed with high-fat diet (HFD) for 12 weeks. At the seventh week, BM-MSCs-EV were given a dose of 120 µg/kg i.v., twice a week for six weeks (12 doses per 6 weeks). Another group was treated with BM-MSCs at a dose of 1 × 106 cell i.v., per rat once every 2 weeks for 6 weeks (3 doses per 6 weeks). BM-MSCs-EV demonstrated superior cardioprotective effects through decreasing serum cardiotoxic markers, cardiac hypoxic state (HIF-1) and cardiac inflammation (NF-κB p65, TNF-α, IL-6). This was accompanied by increased vascular endothelial growth factor (VEGF) and improved cardiac histopathological alterations. Both BM-MSCs-EV and BM-MSCs restored the mitochondrial antioxidant state through the upregulation of UCP2 and MnSOD genes. Besides, mitochondrial Parkin-dependent and -independent mitophagies were regained through the upregulation of (Parkin, PINK1, ULK1, BNIP3L, FUNDC1) and (LC3B). These effects were mediated through the regulation of pAKT, PI3K, Hypoxia, VEGF and NF-κB signaling pathways by an array of secreted microRNAs (miRNAs). Our findings unravel the potential ameliorative effects of BM-MSCs-EV as a comparable new avenue for BM-MSCs for modulating cardiotoxicity that is induced by NASH. Full article
(This article belongs to the Special Issue Exosomes: Biogenesis, Biologic Function and Clinical Potential)
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Review

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16 pages, 2113 KiB  
Review
Exosomes in Neuroblastoma Biology, Diagnosis, and Treatment
by Leila Jahangiri and Tala Ishola
Life 2022, 12(11), 1714; https://doi.org/10.3390/life12111714 - 27 Oct 2022
Cited by 2 | Viewed by 2340
Abstract
Neuroblastoma is an extracranial solid tumour of the developing sympathetic nervous system accounting for circa 15% of deaths due to cancer in paediatric patients. The clinical course of this cancer may be variable, ranging from aggressive progression to regression, while the amplification of [...] Read more.
Neuroblastoma is an extracranial solid tumour of the developing sympathetic nervous system accounting for circa 15% of deaths due to cancer in paediatric patients. The clinical course of this cancer may be variable, ranging from aggressive progression to regression, while the amplification of MYCN in this cancer is linked to poor patient prognosis. Extracellular vesicles are a double membrane encapsulating various cellular components including proteins and nucleic acids and comprise exosomes, apoptotic bodies, and microvesicles. The former can act as mediators between cancer, stromal and immune cells and thereby influence the tumour microenvironment by the delivery of their molecular cargo. In this study, the contribution of extracellular vesicles including exosomes to the biology, prognosis, diagnosis and treatment of neuroblastoma was catalogued, summarised and discussed. The understanding of these processes may facilitate the in-depth dissection of the complexity of neuroblastoma biology, mechanisms of regression or progression, and potential diagnostic and treatment options for this paediatric cancer which will ultimately improve the quality of life of neuroblastoma patients. Full article
(This article belongs to the Special Issue Exosomes: Biogenesis, Biologic Function and Clinical Potential)
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17 pages, 1436 KiB  
Review
Functional Properties of Cancer Epithelium and Stroma-Derived Exosomes in Head and Neck Squamous Cell Carcinoma
by Yang Li, Shengtao Gao, Qi Hu and Fanglong Wu
Life 2022, 12(5), 757; https://doi.org/10.3390/life12050757 - 20 May 2022
Cited by 6 | Viewed by 2626
Abstract
Stroma–cancer cell crosstalk involves a complex signaling network that contributes to tumor progression, including carcinogenesis, angiogenesis, migration, invasion, and therapy resistance in cancers. Exosomes, as extracellular membranous nanovesicles released by almost all types of cells, including tumor cells and stromal cells, play a [...] Read more.
Stroma–cancer cell crosstalk involves a complex signaling network that contributes to tumor progression, including carcinogenesis, angiogenesis, migration, invasion, and therapy resistance in cancers. Exosomes, as extracellular membranous nanovesicles released by almost all types of cells, including tumor cells and stromal cells, play a critical role in signal delivery and material communication, in which the characteristics of their parent cells are reflected. The tumor or stroma-derived exosomes mediate cell–cell communication in the tumor microenvironment by transporting DNA, RNA, proteins, lipids, and metabolites. Recent studies on head and neck squamous cell carcinoma (HNSCC) have demonstrated that tumor-derived exosomes support various tumor biological behaviors, whereas the functional roles of stroma-derived exosomes remain largely unknown. Although these exosomes are emerging as promising targets in early diagnosis, prognostic prediction, and pharmaceutical carriers for antitumor therapy, there are still multiple hurdles to be overcome before they can be used in clinical applications. Herein, we systematically summarize the promotive roles of the epithelium and stroma-derived exosomes in HNSCC and highlight the potential clinical applications of exosomes in the treatment of HNSCC. Full article
(This article belongs to the Special Issue Exosomes: Biogenesis, Biologic Function and Clinical Potential)
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19 pages, 1169 KiB  
Review
Impact of Storage Conditions on EV Integrity/Surface Markers and Cargos
by Ayyanar Sivanantham and Yang Jin
Life 2022, 12(5), 697; https://doi.org/10.3390/life12050697 - 7 May 2022
Cited by 34 | Viewed by 6737
Abstract
Extracellular vesicles (EVs) are small biological particles released into biofluids by every cell. Based on their size, they are classified into small EVs (<100 nm or <200 nm) and medium or large EVs (>200 nm). In recent years, EVs have garnered interest for [...] Read more.
Extracellular vesicles (EVs) are small biological particles released into biofluids by every cell. Based on their size, they are classified into small EVs (<100 nm or <200 nm) and medium or large EVs (>200 nm). In recent years, EVs have garnered interest for their potential medical applications, including disease diagnosis, cell-based biotherapies, targeted drug delivery systems, and others. Currently, the long-term and short-term storage temperatures for biofluids and EVs are −80 °C and 4 °C, respectively. The storage capacity of EVs can depend on their number, size, function, temperature, duration, and freeze–thaw cycles. While these parameters are increasingly studied, the effects of preservation and storage conditions of EVs on their integrity remain to be understood. Knowledge gaps in these areas may ultimately impede the widespread applicability of EVs. Therefore, this review summarizes the current knowledge on the effect of storage conditions on EVs and their stability and critically explores prospective ways for improving long-term storage conditions to ensure EV stability. Full article
(This article belongs to the Special Issue Exosomes: Biogenesis, Biologic Function and Clinical Potential)
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25 pages, 1416 KiB  
Review
Extracellular Vesicles and Cell Pathways Involved in Cancer Chemoresistance
by Lara Console and Mariafrancesca Scalise
Life 2022, 12(5), 618; https://doi.org/10.3390/life12050618 - 21 Apr 2022
Cited by 6 | Viewed by 3569
Abstract
Chemoresistance is a pharmacological condition that allows transformed cells to maintain their proliferative phenotype in the presence of administered anticancer drugs. Recently, extracellular vesicles, including exosomes, have been identified as additional players responsible for the chemoresistance of cancer cells. These are nanovesicles that [...] Read more.
Chemoresistance is a pharmacological condition that allows transformed cells to maintain their proliferative phenotype in the presence of administered anticancer drugs. Recently, extracellular vesicles, including exosomes, have been identified as additional players responsible for the chemoresistance of cancer cells. These are nanovesicles that are released by almost all cell types in both physiological and pathological conditions and contain proteins and nucleic acids as molecular cargo. Extracellular vesicles released in the bloodstream reach recipient cells and confer them novel metabolic properties. Exosomes can foster chemoresistance by promoting prosurvival and antiapoptotic pathways, affecting cancer stem cells and immunotherapies, and stimulating drug efflux. In this context, a crucial role is played by membrane transporters belonging to ABC, SLC, and P-type pump families. These proteins are fundamental in cell metabolism and drug transport in either physiological or pathological conditions. In this review, different roles of extracellular vesicles in drug resistance of cancer cells will be explored. Full article
(This article belongs to the Special Issue Exosomes: Biogenesis, Biologic Function and Clinical Potential)
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34 pages, 1132 KiB  
Review
Non-Exosomal and Exosome-Derived miRNAs as Promising Biomarkers in Canine Mammary Cancer
by Patrícia Petroušková, Nikola Hudáková, Marcela Maloveská, Filip Humeník and Dasa Cizkova
Life 2022, 12(4), 524; https://doi.org/10.3390/life12040524 - 1 Apr 2022
Cited by 10 | Viewed by 6058
Abstract
Canine mammary cancer (CMC), similar to human breast cancer (HBC) in many aspects, is the most common neoplasm associated with significant mortality in female dogs. Due to the limited therapy options, biomarkers are highly desirable for early clinical diagnosis or cancer progression monitoring. [...] Read more.
Canine mammary cancer (CMC), similar to human breast cancer (HBC) in many aspects, is the most common neoplasm associated with significant mortality in female dogs. Due to the limited therapy options, biomarkers are highly desirable for early clinical diagnosis or cancer progression monitoring. Since the discovery of microRNAs (miRNAs or miRs) as post-transcriptional gene regulators, they have become attractive biomarkers in oncological research. Except for intracellular miRNAs and cell-free miRNAs, exosome-derived miRNAs (exomiRs) have drawn much attention in recent years as biomarkers for cancer detection. Analysis of exosomes represents a non-invasive, pain-free, time- and money-saving alternative to conventional tissue biopsy. The purpose of this review is to provide a summary of miRNAs that come from non-exosomal sources (canine mammary tumor, mammary tumor cell lines or canine blood serum) and from exosomes as promising biomarkers of CMC based on the current literature. As is discussed, some of the miRNAs postulated as diagnostic or prognostic biomarkers in CMC were also altered in HBC (such as miR-21, miR-29b, miR-141, miR-429, miR-200c, miR-497, miR-210, miR-96, miR-18a, miR19b, miR-20b, miR-93, miR-101, miR-105a, miR-130a, miR-200c, miR-340, miR-486), which may be considered as potential disease-specific biomarkers in both CMC and HBC. Full article
(This article belongs to the Special Issue Exosomes: Biogenesis, Biologic Function and Clinical Potential)
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15 pages, 935 KiB  
Review
Cancer-Derived Extracellular Vesicles: Their Role in Sarcoma
by Anita Adib, Ruhi Sahu, Shivangi Mohta, Raphael Etomar Pollock and Lucia Casadei
Life 2022, 12(4), 481; https://doi.org/10.3390/life12040481 - 26 Mar 2022
Cited by 2 | Viewed by 2853
Abstract
Soft tissue sarcomas (STS) are rare malignancies with limited responses to anticancer therapy. Extracellular vesicles (EVs) are a heterogeneous group of bi-lipid layer sacs secreted by cells into extracellular space. Investigations of tumor-derived EVs have revealed their functional capabilities, including cell-to-cell communication and [...] Read more.
Soft tissue sarcomas (STS) are rare malignancies with limited responses to anticancer therapy. Extracellular vesicles (EVs) are a heterogeneous group of bi-lipid layer sacs secreted by cells into extracellular space. Investigations of tumor-derived EVs have revealed their functional capabilities, including cell-to-cell communication and their impact on tumorigenesis, progression, and metastasis; however information on the roles of EVs in sarcoma is currently limited. In this review we investigate the role of various EV cargos in sarcoma and the mechanisms by which those cargos can affect the recipient cell phenotype and the aggressivity of the tumor itself. The study of EVs in sarcoma may help establish novel therapeutic approaches that target specific sarcoma subtypes or biologies, thereby improving sarcoma therapeutics in the future. Full article
(This article belongs to the Special Issue Exosomes: Biogenesis, Biologic Function and Clinical Potential)
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