-
Theranostics 2022In recent decades, extracellular vesicles (EVs), as bioactive cell-secreted nanoparticles which are involved in various physiological and pathological processes... (Review)
Review
In recent decades, extracellular vesicles (EVs), as bioactive cell-secreted nanoparticles which are involved in various physiological and pathological processes including cell proliferation, immune regulation, angiogenesis and tissue repair, have emerged as one of the most attractive nanotherapeutics for regenerative medicine. Herein we provide a systematic review of the latest progress of EVs for regenerative applications. Firstly, we will briefly introduce the biogenesis, function and isolation technology of EVs. Then, the underlying therapeutic mechanisms of the native unmodified EVs and engineering strategies of the modified EVs as regenerative entities will be discussed. Subsequently, the main focus will be placed on the tissue repair and regeneration applications of EVs on various organs including brain, heart, bone and cartilage, liver and kidney, as well as skin. More importantly, current clinical trials of EVs for regenerative medicine will also be briefly highlighted. Finally, the future challenges and insightful perspectives of the currently developed EV-based nanotherapeutics in biomedicine will be discussed. In short, the bioactive EV-based nanotherapeutics have opened new horizons for biologists, chemists, nanoscientists, pharmacists, as well as clinicians, making possible powerful tools and therapies for regenerative medicine.
Topics: Extracellular Vesicles; Kidney; Nanoparticles; Regenerative Medicine; Wound Healing
PubMed: 35836815
DOI: 10.7150/thno.72812 -
Ageing Research Reviews Mar 2023The prevalence of diabetes among the elderly population is significant and rising annually. One of the most severe and frequent complications of diabetes mellitus is the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The prevalence of diabetes among the elderly population is significant and rising annually. One of the most severe and frequent complications of diabetes mellitus is the diabetic wound, which has long-term negative effects on patients' finances, mental health, and functional abilities. Exosomes, a cell-free therapy, have emerged as a promising novel treatment for diabetic wounds, but their mechanism is still not entirely understood. Therefore, we conducted this meta-analysis to assess the effectiveness of exosomes in the management of diabetic wounds.
METHODS
We searched PubMed, the Cochrane Library, EMBASE, and Web of Science for pertinent studies that described the therapeutic benefits of exosomes on diabetic wound models that were released before October 17, 2022. The outcome indicators consisted of wound healing rate, neovascular density, re-epithelialization rate, collagen deposition, scar width, and inflammatory factors. RevMan 5.4 software was used to conduct all statistical analyses.
RESULTS
A total of 21 studies with 323 animals were identified in this meta-analysis. Pooled analyses demonstrated that exosome therapy was shown to be superior to control therapy in terms of wound healing rate (SMD = 5.42; 95 %CI = 4.40-6.44; P < 0.00001), neovascular density (SMD = 5.48; 95 %CI = 4.31-6.64; P < 0.00001), re-epithelialization rate (SMD = 5.06; 95 %CI = 3.75-6.37; P < 0.00001), collagen deposition (SMD = 4.78; 95 %CI = 3.58-5.98; P < 0.00001), scar width (SMD = -8.10; 95 %CI = -10.31 to -5.89; P < 0.00001). Additionally, the expression of inflammatory factors was significantly downregulated in the exosome treatment group.
CONCLUSIONS
According to this meta-analysis of the current trials, exosome therapy can enhance the quality of diabetic wounds, especially when used in conjunction with novel dressings. To demonstrate the most efficient exosomes and therapeutic parameters for the treatment of diabetic wounds, future studies should conduct sizable, randomized, double-blind trials with high-quality, long-term follow-ups.
Topics: Aged; Animals; Humans; Cicatrix; Exosomes; Wound Healing; Diabetes Mellitus; Collagen; Randomized Controlled Trials as Topic
PubMed: 36669689
DOI: 10.1016/j.arr.2023.101858 -
International Journal of Molecular... Aug 2023The use of platelet-rich plasma (PRP) has gained increasing interest in recent decades. The platelet secretome contains a multitude of growth factors, cytokines,... (Review)
Review
The use of platelet-rich plasma (PRP) has gained increasing interest in recent decades. The platelet secretome contains a multitude of growth factors, cytokines, chemokines, and other biological biomolecules. In recent years, developments in the field of platelets have led to new insights, and attention has been focused on the platelets' released extracellular vesicles (EVs) and their role in intercellular communication. In this context, the aim of this review was to compile the current evidence on PRP-derived extracellular vesicles to identify the advantages and limitations fortheir use in the upcoming clinical applications. A total of 172 articles were identified during the systematic literature search through two databases (PubMed and Web of Science). Twenty publications met the inclusion criteria and were included in this review. According to the results, the use of PRP-EVs in the clinic is an emerging field of great interest that represents a promising therapeutic option, as their efficacy has been demonstrated in the majority of fields of applications included in this review. However, the lack of standardization along the procedures in both the field of PRP and the EVs makes it extremely challenging to compare results among studies. Establishing standardized conditions to ensure optimized and detailed protocols and define parameters such as the dose or the EV origin is therefore urgent. Further studies to elucidate the real contribution of EVs to PRP in terms of composition and functionality should also be performed. Nevertheless, research on the field provides promising results and a novel basis to deal with the regenerative medicine and drug delivery fields in the future.
Topics: Blood Platelets; Cell Communication; Extracellular Vesicles; Platelet-Rich Plasma; Regenerative Medicine
PubMed: 37685849
DOI: 10.3390/ijms241713043 -
International Journal of Molecular... Sep 2022The pathophysiology of chronic rhinosinusitis (CRS) is multifactorial and not entirely clear. The objective of the review was to examine the current state of knowledge... (Review)
Review
The pathophysiology of chronic rhinosinusitis (CRS) is multifactorial and not entirely clear. The objective of the review was to examine the current state of knowledge concerning the role of exosomes in CRS. For this systematic review, we searched PubMed/MEDLINE, Scopus, CENTRAL, and Web of Science databases for studies published until 7 August 2022. Only original research articles describing studies published in English were included. Reviews, book chapters, case studies, conference papers, and opinions were excluded. The quality of the evidence was assessed with the modified Office and Health Assessment and Translation (OHAT) Risk of Bias Rating Tool for Human and Animal Studies. Of 250 records identified, 17 were eligible, all of which had a low to moderate risk of overall bias. Presented findings indicate that exosomal biomarkers, including proteins and microRNA, act as promising biomarkers in the diagnostics and prognosis of CRS patients and, in addition, may contribute to finding novel therapeutic targets. Exosomes reflecting tissue proteomes are excellent, highly available material for studying proteomic alterations noninvasively. The first steps have already been taken, but more advanced research on nasal exosomes is needed, which might open a wider door for individualized medicine in CRS.
Topics: Animals; Biomarkers; Chronic Disease; Exosomes; Humans; MicroRNAs; Proteome; Proteomics; Rhinitis; Sinusitis
PubMed: 36232588
DOI: 10.3390/ijms231911284 -
Cytotherapy Mar 2023Evidence regarding the extent that mesenchymal stromal cells (MSCs) may improve clinical outcomes in patients with coronavirus disease 2019 (COVID-19) has been limited... (Meta-Analysis)
Meta-Analysis
BACKGROUND AIMS
Evidence regarding the extent that mesenchymal stromal cells (MSCs) may improve clinical outcomes in patients with coronavirus disease 2019 (COVID-19) has been limited by marked inter-study heterogeneity, inconsistent product characterization and appreciable risk of bias (RoB). Given the evolution of treatment options and trajectory of the pandemic, an updated analysis of high-quality evidence from randomized controlled trials is needed for a timely and conclusive understanding of the effectiveness of MSCs.
METHODS
A systematic literature search through March 30, 2022, identified all English language, full-text randomized controlled trials examining the use of MSCs in the treatment of COVID-19.
RESULTS
Eight studies were identified (316 patients, 165 administered MSCs and 151 controls). Controls evolved significantly over time with a broad range of comparison treatments. All studies reported mortality at study endpoint. Random effects meta-analysis revealed that MSCs decreased relative risk of death (risk ratio, 0.63, 95% confidence interval, 0.42-0.94, P = 0.02, I = 14%) with no significant difference in absolute risk of death. MSCs decreased length of hospital stay and C-reactive protein levels and increased odds of clinical improvement at study endpoint compared with controls. Rates of adverse events and severe adverse events were similar between MSC and control groups. Only two (25%) studies reported all four International Society for Cell & Gene Therapy criteria for MSC characterization. Included studies had low (n = 7) or some (n = 1) concerns regarding RoB.
CONCLUSIONS
MSCs may reduce risk of death in patients with severe or critical COVID-19 and improve secondary clinical outcomes. Variable outcome reporting, inconsistent product characterization and variable control group treatments remain barriers to higher-quality evidence and may constrain clinical usage. A master protocol is proposed and appears necessary for accelerated translation of higher-quality evidence for future applications of MSC therapy.
Topics: Humans; COVID-19; SARS-CoV-2; Randomized Controlled Trials as Topic; Pandemics; Mesenchymal Stem Cells
PubMed: 36333234
DOI: 10.1016/j.jcyt.2022.10.003 -
Translational Research : the Journal of... Jun 2022Extensive research is focused on the role of liquid biopsy in pancreatic cancer since reliable diagnostic and follow-up biomarkers represent an unmet need for this... (Meta-Analysis)
Meta-Analysis Review
Extensive research is focused on the role of liquid biopsy in pancreatic cancer since reliable diagnostic and follow-up biomarkers represent an unmet need for this highly lethal malignancy. We performed a systematic review and meta-analysis on the prognostic value of exosomal biomarkers in pancreatic ductal adenocarcinoma (PDAC). MEDLINE, Embase, Scopus, Web of Science, and CENTRAL were systematically searched on the 18th of January, 2021 for studies reporting on the differences in overall (OS) and progression-free survival (PFS) in PDAC patients with positive vs negative exosomal biomarkers isolated from blood. The random-effects model estimated pooled multivariate-adjusted (AHR) and univariate hazard ratios (UHRs) with 95% confidence intervals (CIs). Eleven studies comprising 634 patients were eligible for meta-analysis. Detection of positive exosomal biomarkers indicated increased risk of mortality (UHR = 2.81, CI:1.31-6,00, I = 88.7%, P < 0.001), and progression (UHR = 3.33, CI: 2.33-4.77, I = 0, P = 0.879) across various disease stages. Positive exosomal biomarkers identified preoperatively revealed a higher risk of mortality in resectable stages (UHR = 5.55, CI: 3.24-9.49, I = 0, P = 0.898). The risk of mortality in unresectable stages was not significantly increased with positive exosomal biomarkers (UHR = 2.51, CI: 0.55-11.43, I = 90.3%, P < 0.001). Detectable exosomal micro ribonucleic acids were associated with a decreased OS (UHR = 4.08, CI: 2.16-7.69, I = 46.9%, P = 0.152) across various stages. Our results reflect the potential of exosomal biomarkers for prognosis evaluation in PDAC. The associated heterogeneity reflects the variability of study methods and need for their uniformization before transition to clinical use.
Topics: Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Exosomes; Humans; Pancreatic Neoplasms; Prognosis
PubMed: 35066189
DOI: 10.1016/j.trsl.2022.01.001 -
International Journal of Molecular... Dec 2022The pathophysiology of allergic rhinitis (AR), one of the most common diseases in the world, is still not sufficiently understood. Extracellular vesicles (EVs), which... (Review)
Review
The pathophysiology of allergic rhinitis (AR), one of the most common diseases in the world, is still not sufficiently understood. Extracellular vesicles (EVs), which are secreted by host and bacteria cells and take part in near and distant intracellular communication, can provide information about AR. Recently, attention has been drawn to the potential use of EVs as biomarkers, vaccines, or transporters for drug delivery. In this review, we present an up-to-date literature overview on EVs in AR to reveal their potential clinical significance in this condition. A comprehensive and systematic literature search was conducted following PRISMA statement guidelines for original, completed articles, available in English concerning EVs and AR. For this purpose, PubMed/MEDLINE, Scopus, Web of Science, and Cochrane, were searched up until 10 Novenmber 2022. From 275 records, 18 articles were included for analysis. The risk of bias was assessed for all studies as low or moderate risk of overall bias using the Office and Health Assessment and Translation Risk of Bias Rating Tool for Human and Animal Studies. We presented the role of exosomes in the pathophysiology of AR and highlighted the possibility of using exosomes as biomarkers and treatment in this disease.
Topics: Animals; Humans; Rhinitis, Allergic; Extracellular Vesicles; Exosomes; Biomarkers; Biological Transport
PubMed: 36613810
DOI: 10.3390/ijms24010367 -
Stem Cell Research & Therapy Jun 2022Primary Sjögren's syndrome (pSS) is a diffuse connective tissue disease characterized by the invasion of exocrine glands such as lacrimal and salivary glands, abnormal... (Review)
Review
Primary Sjögren's syndrome (pSS) is a diffuse connective tissue disease characterized by the invasion of exocrine glands such as lacrimal and salivary glands, abnormal proliferation of T and B lymphocytes, and infiltration of tissue lymphocytes. With the development of modern medicine, although research on the pathogenesis, diagnosis, and treatment of pSS has made significant progress, its pathogenesis has not been fully understood. Meanwhile, in the era of individualized treatment, it remains essential to further explore early diagnosis and treatment methods. Exosomes, small vesicles containing proteins and nucleic acids, are a subtype of extracellular vesicles secreted by various cells and present in various body fluids. Exosomes contribute to a variety of biological functions, including intercellular signal transduction and pathophysiological processes, and may play a role in immune tolerance. Therefore, exosomes are key to understanding the pathogenesis of diseases. Exosomes can also be used as a therapeutic tool for pSS because of their biodegradability, low immunogenicity and toxicity, and the ability to bypass the blood-brain barrier, implying the prospect of a broad application in the context of pSS. Here, we systematically review the isolation, identification, tracing, and mode of action of extracellular vesicles, especially exosomes, as well as the research progress in the pathogenesis, diagnosis, and treatment of pSS.
Topics: B-Lymphocytes; Exosomes; Extracellular Vesicles; Humans; Salivary Glands; Sjogren's Syndrome
PubMed: 35659085
DOI: 10.1186/s13287-022-02912-1 -
International Journal of Molecular... Oct 2023Mesenchymal stem cell (MSC)-based exosomes have garnered attention as a viable therapeutic for post-traumatic cartilage injury and osteoarthritis of the knee; however,... (Review)
Review
Mesenchymal stem cell (MSC)-based exosomes have garnered attention as a viable therapeutic for post-traumatic cartilage injury and osteoarthritis of the knee; however, efforts for application have been limited due to issues with variable dosing and rapid clearance in vivo. Scaffolds laden with MSC-based exosomes have recently been investigated as a solution to these issues. Here, we review in vivo studies and highlight key strengths and potential clinical uses of exosome-scaffold therapeutics for treatment of post-traumatic cartilage injury and osteoarthritis. In vivo animal studies were gathered using keywords related to the topic, revealing 466 studies after removal of duplicate papers. Inclusion and exclusion criteria were applied for abstract screening and full-text review. Thirteen relevant studies were identified for analysis and extraction. Three predominant scaffold subtypes were identified: hydrogels, acellular extracellular matrices, and hyaluronic acid. Each scaffold-exosome design showcased unique properties with relation to gross findings, tissue histology, biomechanics, and gene expression. All designs demonstrated a reduction in inflammation and induction of tissue regeneration. The results of our review show that current exosome-scaffold therapeutics demonstrate the capability to halt and even reverse the course of post-traumatic cartilage injury and osteoarthritis. While this treatment modality shows incredible promise, future research should aim to characterize long-term biocompatibility and optimize scaffold designs for human treatment.
Topics: Animals; Humans; Osteoarthritis, Knee; Exosomes; Cartilage Diseases; Knee Joint; Cartilage; Cartilage, Articular; Tissue Scaffolds
PubMed: 37894859
DOI: 10.3390/ijms242015178 -
Journal of Nanobiotechnology Oct 2023This systematic review and meta-analysis aimed to evaluate the efficacy of engineered extracellular vesicles (EEVs) in the treatment of ischemic stroke (IS) in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review and meta-analysis aimed to evaluate the efficacy of engineered extracellular vesicles (EEVs) in the treatment of ischemic stroke (IS) in preclinical studies and to compare them with natural extracellular vesicles (EVs). The systematic review provides an up-to-date overview of the current state of the literature on the use of EEVs for IS and informs future research in this area.
METHODS
We searched PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus databases for peer-reviewed preclinical studies on the therapeutic effect of EEVs on IS.Databases ranged from the inception to August 1, 2023. The outcome measures included infarct volumes, neurological scores, behavioral scores, apoptosis rates, numbers of neurons, and levels of IL-1β, IL-6, and TNF-α. The CAMARADES checklist was used to assess the quality and bias risks of the studies. All statistical analyses were performed using RevMan 5.4 software.
RESULTS
A total of 28 studies involving 1760 animals met the inclusion criteria. The results of the meta-analysis showed that compared to natural EVs, EEVs reduced infarct volume (percentage: SMD = -2.33, 95% CI: -2.92, -1.73; size: SMD = -2.36, 95% CI: -4.09, -0.63), improved neurological scores (mNSS: SMD = -1.78, 95% CI: -2.39, -1.17; Zea Longa: SMD = -2.75, 95% CI: -3.79, -1.71), promoted behavioral recovery (rotarod test: SMD = 2.50, 95% CI: 1.81, 3.18; grid-walking test: SMD = -3.45, 95% CI: -5.15, -1.75; adhesive removal test: SMD = -2.60, 95% CI: -4.27, -0.93; morris water maze test: SMD = -3.91, 95% CI: -7.03, -0.79), and reduced the release of proinflammatory factors (IL-1β: SMD = -2.02, 95% CI: -2.77, -1.27; IL-6: SMD = -3.01, 95% CI: -4.47, -1.55; TNF-α: SMD = -2.72, 95% CI: -4.30, -1.13), increasing the number of neurons (apoptosis rate: SMD = -2.24, 95% CI: -3.32, -1.16; the number of neurons: SMD = 3.70, 95% CI: 2.44, 4.96). The funnel plots for the two main outcome measures were asymmetric, indicating publication bias. The median score on the CAMARADES checklist was 7 points (IQR: 6-9).
CONCLUSIONS
This meta-analysis shows that EEVs are superior to natural EVs for the treatment of IS. However, research in this field is still at an early stage, and more research is needed to fully understand the potential therapeutic mechanism of EEVs and their potential use in the treatment of IS.
PROSPERO REGISTRATION NUMBER
CRD42022368744.
Topics: Animals; Ischemic Stroke; Interleukin-6; Tumor Necrosis Factor-alpha; Extracellular Vesicles; Infarction
PubMed: 37904204
DOI: 10.1186/s12951-023-02114-8