Research

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13 pages, 2284 KiB

Open AccessArticle

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://0-doi-org.brum.beds.ac.uk/10.3390/life12101567 - 09 Oct 2022

Cited by 8 | Viewed by 1853

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

Open AccessArticle

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://0-doi-org.brum.beds.ac.uk/10.3390/life12091392 - 06 Sep 2022

Cited by 5 | Viewed by 1938

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

Open AccessArticle

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://0-doi-org.brum.beds.ac.uk/10.3390/life12030355 - 28 Feb 2022

Cited by 2 | Viewed by 2667

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

Open AccessReview

Exosomes in Neuroblastoma Biology, Diagnosis, and Treatment

by Leila Jahangiri and Tala Ishola

Life 2022, 12(11), 1714; https://0-doi-org.brum.beds.ac.uk/10.3390/life12111714 - 27 Oct 2022

Cited by 2 | Viewed by 1892

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

Open AccessReview

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://0-doi-org.brum.beds.ac.uk/10.3390/life12050757 - 20 May 2022

Cited by 6 | Viewed by 2172

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

Open AccessReview

Impact of Storage Conditions on EV Integrity/Surface Markers and Cargos

by Ayyanar Sivanantham and Yang Jin

Life 2022, 12(5), 697; https://0-doi-org.brum.beds.ac.uk/10.3390/life12050697 - 07 May 2022

Cited by 24 | Viewed by 5276

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

Open AccessReview

Extracellular Vesicles and Cell Pathways Involved in Cancer Chemoresistance

by Lara Console and Mariafrancesca Scalise

Life 2022, 12(5), 618; https://0-doi-org.brum.beds.ac.uk/10.3390/life12050618 - 21 Apr 2022

Cited by 4 | Viewed by 2830

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

Open AccessReview

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://0-doi-org.brum.beds.ac.uk/10.3390/life12040524 - 01 Apr 2022

Cited by 7 | Viewed by 5185

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

Open AccessReview

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://0-doi-org.brum.beds.ac.uk/10.3390/life12040481 - 26 Mar 2022

Cited by 2 | Viewed by 2466

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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