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The Role of Exosomes in Health and Disease 2.0
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The Role of Exosomes in Health and Disease 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 20961

Special Issue Editor

Prof. Dr. Vincenzo Lionetti

E-Mail Website
Guest Editor
Professor, MD, PhD, Unit of Translational Critical Care Medicine, Scuola Superiore Sant'Anna, Pisa, Italy
Interests: cardioprotection; epigenetics; perioperative medicine; animal models; exosomes; ristoceutica
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Exosomes are the smallest cell-released vesicles with the potential to transfer proteins, lipids, metabolites, small RNAs, messenger RNAs, or DNA between several cells exposed to different microenvironments via extracellular fluid, lymph, and bloodstream.

Exosomes have emerged as a new type of therapeutic and diagnostic (theranostic) tool in the noninvasive assessment of tissue response to stress, injury, surgery, drugs, foods or rehabilitation, and in the development of reliable organ-protective intensive therapy.

This Special Issue will discuss the recent advances in the field of exosomes as endogenous mediators of physiological and pathological conditions, focusing on the potential use of these nanovesicles as biomarkers or therapeutic agents. All types of articles including original research, review are welcomed.

Prof. Dr. Vincenzo Lionetti
Guest Editor

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Published Papers (7 papers)

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Research

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10 pages, 1907 KiB  
Article
Paper-Based Exosomal MicroRNA-21 Detection for Wound Monitoring: A Proof of Concept and Clinical Validation Trial Study
by Shin-Chen Pan, Chi-Hung Lai, Van-Truc Vu, Cao-An Vu, Chun-Jen Huang, Chao-Min Cheng and Wen-Yih Chen
Int. J. Mol. Sci. 2023, 24(12), 9822; https://doi.org/10.3390/ijms24129822 - 6 Jun 2023
Viewed by 1457
Abstract
Emerging evidence has shown that microRNAs play pivotal roles in wound healing. MicroRNA-21 (miR-21) was previously found to upregulate in order to fulfill an anti-inflammation role for wounds. Exosomal miRNAs have been identified and explored as essential markers for diagnostic medicine. However, the [...] Read more.
Emerging evidence has shown that microRNAs play pivotal roles in wound healing. MicroRNA-21 (miR-21) was previously found to upregulate in order to fulfill an anti-inflammation role for wounds. Exosomal miRNAs have been identified and explored as essential markers for diagnostic medicine. However, the role of exosomal miR-21 in wounds has yet to be well studied. In order to facilitate the early management of poorly healing wounds, we developed an easy-to-use, rapid, paper-based microfluidic-exosomal miR-21 extraction device to determine wound prognosis in a timely manner. We isolated and then quantitatively examined exosomal miR-21 in wound fluids from normal tissues and acute and chronic wounds. Eight improving wounds displayed lower levels of exosomal miR-21 expression after wound debridement. However, four instances of increased exosomal miR-21 expression levels were notably associated with patients with poor healing wounds despite aggressive wound debridement, indicating a predictive role of tissue exosomal miR-21 for wound outcome. Paper-based nucleic acid extraction device provides a rapid and user-friendly approach for evaluating exosomal miR-21 in wound fluids as a means of monitoring wounds. Our data suggest that tissue exosomal miR-21 is a reliable marker for determining current wound status. Full article
(This article belongs to the Special Issue The Role of Exosomes in Health and Disease 2.0)
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14 pages, 2345 KiB  
Article
The Exosome-like Vesicles of Giardia Assemblages A, B, and E Are Involved in the Delivering of Distinct Small RNA from Parasite to Parasite
by Lautaro Natali, Gabriel Luna Pizarro, Sofía Moyano, Benjamin de la Cruz-Thea, Juliana Musso, Andrea S. Rópolo, Norbert Eichner, Gunter Meister, Melina M. Musri, Constanza Feliziani and María C. Touz
Int. J. Mol. Sci. 2023, 24(11), 9559; https://doi.org/10.3390/ijms24119559 - 31 May 2023
Cited by 10 | Viewed by 2272
Abstract
The genetically related assemblages of the intestinal protozoa parasite Giardia lamblia are morphologically indistinguishable and are often derived from specific hosts. The Giardia assemblages are separated by large genetic distances, which might account for their relevant biological and pathogenic differences. In this work, [...] Read more.
The genetically related assemblages of the intestinal protozoa parasite Giardia lamblia are morphologically indistinguishable and are often derived from specific hosts. The Giardia assemblages are separated by large genetic distances, which might account for their relevant biological and pathogenic differences. In this work, we analyzed the RNAs cargo released into exosomal-like vesicles (ElVs) by the assemblages A and B, which differentially infect humans, and the assemblage E, which infects hoofed animals. The RNA sequencing analysis revealed that the ElVs of each assemblage contained distinct small RNA (sRNA) biotypes, suggesting a preference for specific packaging in each assemblage. These sRNAs were classified into three categories, ribosomal-small RNAs (rsRNAs), messenger-small RNAs (msRNAs), and transfer-small RNAs (tsRNAs), which may play a regulatory role in parasite communication and contribute to host-specificity and pathogenesis. Uptake experiments showed, for the first time, that ElVs were successfully internalized by the parasite trophozoites. Furthermore, we observed that the sRNAs contained inside these ElVs were first located below the plasma membrane but then distributed along the cytoplasm. Overall, the study provides new insights into the molecular mechanisms underlying the host-specificity and pathogenesis of G. lamblia and highlights the potential role of sRNAs in parasite communication and regulation. Full article
(This article belongs to the Special Issue The Role of Exosomes in Health and Disease 2.0)
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15 pages, 3578 KiB  
Article
Investigation of the Presence of DNA in Human Blood Plasma Small Extracellular Vesicles
by Kristína Lichá, Michal Pastorek, Gabriela Repiská, Peter Celec and Barbora Konečná
Int. J. Mol. Sci. 2023, 24(6), 5915; https://doi.org/10.3390/ijms24065915 - 21 Mar 2023
Cited by 10 | Viewed by 2590
Abstract
Extracellular DNA (ecDNA) is DNA outside of cells, which is a result of various mechanisms. EcDNA is believed to be a cause of various pathogeneses as well as their potential biomarker. EcDNA is believed to also be part of small extracellular vesicles (sEVs) [...] Read more.
Extracellular DNA (ecDNA) is DNA outside of cells, which is a result of various mechanisms. EcDNA is believed to be a cause of various pathogeneses as well as their potential biomarker. EcDNA is believed to also be part of small extracellular vesicles (sEVs) from cell cultures. If ecDNA is present in sEVs in plasma, their membrane may protect it from degradation by deoxyribonucleases. Moreover, sEVs play a role in the intercellular communication, and they can therefore transfer ecDNA between cells. The aim of this study was to investigate the presence of ecDNA in sEVs isolated from fresh human plasma by the ultracentrifugation and density gradient, which serves to exclude the co-isolation of non-sEVs compartments. The novelty of the current study is the investigation of the localization and subcellular origin of the ecDNA associated with sEVs in plasma, as well as the estimation of the approximate concentration. The cup-shaped sEVs were confirmed by transmission electron microscopy. The highest concentration of particles was in the size of 123 nm. The presence of the sEVs markers CD9 and TSG101 was confirmed by western blot. It was found that 60–75% of DNA is on the surface of sEVs, but a part of the DNA is localized inside the sEVs. Moreover, both nuclear and mitochondrial DNA were present in plasma EVs. Further studies should focus on the potential harmful autoimmune effect of DNA carried by plasma EVs or specifically sEVs. Full article
(This article belongs to the Special Issue The Role of Exosomes in Health and Disease 2.0)
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Review

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52 pages, 2287 KiB  
Review
Potential Pathogenic Impact of Cow’s Milk Consumption and Bovine Milk-Derived Exosomal MicroRNAs in Diffuse Large B-Cell Lymphoma
by Bodo C. Melnik, Rudolf Stadler, Ralf Weiskirchen, Claus Leitzmann and Gerd Schmitz
Int. J. Mol. Sci. 2023, 24(7), 6102; https://doi.org/10.3390/ijms24076102 - 23 Mar 2023
Cited by 8 | Viewed by 4291
Abstract
Epidemiological evidence supports an association between cow’s milk consumption and the risk of diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin lymphoma worldwide. This narrative review intends to elucidate the potential impact of milk-related agents, predominantly milk-derived exosomes (MDEs) and their microRNAs [...] Read more.
Epidemiological evidence supports an association between cow’s milk consumption and the risk of diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin lymphoma worldwide. This narrative review intends to elucidate the potential impact of milk-related agents, predominantly milk-derived exosomes (MDEs) and their microRNAs (miRs) in lymphomagenesis. Upregulation of PI3K-AKT-mTORC1 signaling is a common feature of DLBCL. Increased expression of B cell lymphoma 6 (BCL6) and suppression of B lymphocyte-induced maturation protein 1 (BLIMP1)/PR domain-containing protein 1 (PRDM1) are crucial pathological deviations in DLBCL. Translational evidence indicates that during the breastfeeding period, human MDE miRs support B cell proliferation via epigenetic upregulation of BCL6 (via miR-148a-3p-mediated suppression of DNA methyltransferase 1 (DNMT1) and miR-155-5p/miR-29b-5p-mediated suppression of activation-induced cytidine deaminase (AICDA) and suppression of BLIMP1 (via MDE let-7-5p/miR-125b-5p-targeting of PRDM1). After weaning with the physiological termination of MDE miR signaling, the infant’s BCL6 expression and B cell proliferation declines, whereas BLIMP1-mediated B cell maturation for adequate own antibody production rises. Because human and bovine MDE miRs share identical nucleotide sequences, the consumption of pasteurized cow’s milk in adults with the continued transfer of bioactive bovine MDE miRs may de-differentiate B cells back to the neonatal “proliferation-dominated” B cell phenotype maintaining an increased BLC6/BLIMP1 ratio. Persistent milk-induced epigenetic dysregulation of BCL6 and BLIMP1 expression may thus represent a novel driving mechanism in B cell lymphomagenesis. Bovine MDEs and their miR cargo have to be considered potential pathogens that should be removed from the human food chain. Full article
(This article belongs to the Special Issue The Role of Exosomes in Health and Disease 2.0)
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24 pages, 5297 KiB  
Review
Placenta-Derived Extracellular Vesicles in Pregnancy Complications and Prospects on a Liquid Biopsy for Hemoglobin Bart’s Disease
by Piya Chaemsaithong, Suchaya Luewan, Mana Taweevisit, Wararat Chiangjong, Pisut Pongchaikul, Paul Scott Thorner, Theera Tongsong and Somchai Chutipongtanate
Int. J. Mol. Sci. 2023, 24(6), 5658; https://doi.org/10.3390/ijms24065658 - 16 Mar 2023
Cited by 5 | Viewed by 3061
Abstract
Extracellular vesicles (EVs) are nano-scaled vesicles released from all cell types into extracellular fluids and specifically contain signature molecules of the original cells and tissues, including the placenta. Placenta-derived EVs can be detected in maternal circulation at as early as six weeks of [...] Read more.
Extracellular vesicles (EVs) are nano-scaled vesicles released from all cell types into extracellular fluids and specifically contain signature molecules of the original cells and tissues, including the placenta. Placenta-derived EVs can be detected in maternal circulation at as early as six weeks of gestation, and their release can be triggered by the oxygen level and glucose concentration. Placental-associated complications such as preeclampsia, fetal growth restriction, and gestational diabetes have alterations in placenta-derived EVs in maternal plasma, and this can be used as a liquid biopsy for the diagnosis, prediction, and monitoring of such pregnancy complications. Alpha-thalassemia major (“homozygous alpha-thalassemia-1”) or hemoglobin Bart’s disease is the most severe form of thalassemia disease, and this condition is lethal for the fetus. Women with Bart’s hydrops fetalis demonstrate signs of placental hypoxia and placentomegaly, thereby placenta-derived EVs provide an opportunity for a non-invasive liquid biopsy of this lethal condition. In this article, we introduced clinical features and current diagnostic markers of Bart’s hydrops fetalis, extensively summarize the characteristics and biology of placenta-derived EVs, and discuss the challenges and opportunities of placenta-derived EVs as part of diagnostic tests for placental complications focusing on Bart’s hydrop fetalis. Full article
(This article belongs to the Special Issue The Role of Exosomes in Health and Disease 2.0)
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18 pages, 1007 KiB  
Review
The Roles of Exosomal Proteins: Classification, Function, and Applications
by Xin-Xin Li, Lu-Xuan Yang, Chuang Wang, Hui Li, De-Shun Shi and Jian Wang
Int. J. Mol. Sci. 2023, 24(4), 3061; https://doi.org/10.3390/ijms24043061 - 4 Feb 2023
Cited by 22 | Viewed by 3809
Abstract
Exosome, a subpopulation of extracellular vesicles, plays diverse roles in various biological processes. As one of the most abundant components of exosomes, exosomal proteins have been revealed to participate in the development of many diseases, such as carcinoma, sarcoma, melanoma, neurological disorders, immune [...] Read more.
Exosome, a subpopulation of extracellular vesicles, plays diverse roles in various biological processes. As one of the most abundant components of exosomes, exosomal proteins have been revealed to participate in the development of many diseases, such as carcinoma, sarcoma, melanoma, neurological disorders, immune responses, cardiovascular diseases, and infection. Thus, understanding the functions and mechanisms of exosomal proteins potentially assists clinical diagnosis and targeted delivery of therapies. However, current knowledge about the function and application of exosomal proteins is still limited. In this review, we summarize the classification of exosomal proteins, and the roles of exosomal proteins in exosome biogenesis and disease development, as well as in the clinical applications. Full article
(This article belongs to the Special Issue The Role of Exosomes in Health and Disease 2.0)
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13 pages, 933 KiB  
Review
Adipose-Secreted Exosomes and Their Pathophysiologic Effects on Skeletal Muscle
by Binglin Yue, Hui Wang, Xin Cai, Jiabo Wang, Zhixin Chai, Wei Peng, Shi Shu, Changqi Fu and Jincheng Zhong
Int. J. Mol. Sci. 2022, 23(20), 12411; https://doi.org/10.3390/ijms232012411 - 17 Oct 2022
Cited by 6 | Viewed by 2621
Abstract
Due to its prominent secretory activity, adipose tissue (AT) is now considered a major player in the crosstalk between organs, especially with skeletal muscle. In which, exosomes are effective carriers for the intercellular material transfer of a wide range of molecules that can [...] Read more.
Due to its prominent secretory activity, adipose tissue (AT) is now considered a major player in the crosstalk between organs, especially with skeletal muscle. In which, exosomes are effective carriers for the intercellular material transfer of a wide range of molecules that can influence a series of physiological and pathological processes in recipient cells. Considering their underlying roles, the regulatory mechanisms of adipose-secreted exosomes and their cellular crosstalk with skeletal muscle have received great attention in the field. In this review, we describe what is currently known of adipose-secreted exosomes, as well as their applications in skeletal muscle pathophysiology. Full article
(This article belongs to the Special Issue The Role of Exosomes in Health and Disease 2.0)
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