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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 -
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 -
Frontiers in Physiology 2023Exercise-derived exosomes have been identified as novel players in mediating cell-to-cell communication in the beneficial effects of improving cardiovascular disease... (Review)
Review
Exercise-derived exosomes have been identified as novel players in mediating cell-to-cell communication in the beneficial effects of improving cardiovascular disease (CVD). This review aimed to systematically investigate exosomes as delivery tools for the benefits of exercise in the prevention and treatment of CVD and summarize these outcomes with an overview of their therapeutic implications. Among the 1417 articles obtained in nine database searches (PubMed, EBSCO, Embase, Web of Science, CENTRAL, Ovid, Science Direct, Scopus, and Wiley), 12 articles were included based on eligibility criteria. The results indicate that exercise increases the release of exosomes, increasing exosomal markers (TSG101, CD63, and CD81) and exosome-carried miRNAs (miR-125b-5p, miR-122-5p, miR-342-5p, miR-126, miR-130a, miR-138-5p, and miR-455). These miRNAs mainly regulate the expression of MAPK, NF-kB, VEGF, and Caspase to protect the cardiovascular system. Moreover, the outcome indicators of myocardial apoptosis and myocardial infarction volume are significantly reduced following exercise-induced exosome release, and angiogenesis, microvessel density and left ventricular ejection fraction are significantly increased, as well as alleviating myocardial fibrosis following exercise-induced exosome release. Collectively, these results further confirm that exercise-derived exosomes have a beneficial role in potentially preventing and treating CVD and support the use of exercise-derived exosomes in clinical settings.
PubMed: 37841310
DOI: 10.3389/fphys.2023.1190095 -
Advanced Healthcare Materials Dec 2023Heart failure, a pervasive global health burden, necessitates innovative therapeutic strategies. Extracellular vesicles (EVs) have emerged as promising contenders for...
Heart failure, a pervasive global health burden, necessitates innovative therapeutic strategies. Extracellular vesicles (EVs) have emerged as promising contenders for cardiac repair, owing to their profound influence on fibrosis and inflammation. Merging EVs with biomaterials holds the potential for a synergistic leap in therapeutic efficacy. In this review, the impact of combining EVs with biomaterials in preclinical heart failure models is scrutinized. Fifteen studies, predominantly employing mesenchymal stromal cell-derived EVs along with hyaluronic acid or peptides in coronary ligation models, meet these stringent criteria. The amalgamation of EVs and biomaterials consistently enhances cardiac ejection fraction (1.39; 95% CI: 0.68, 2.11; p = 0.0001) and fractional shortening (1.46, 95% CI: 0.70, 2.22; p = 0.0002) compared to EV monotherapy. Secondary outcomes similarly showcased improvement in the combined treatment group. Although the number of studies analyzed is modest, no indications of publication bias surface. In summary, combination therapy with EVs and biomaterials enhances therapeutic benefit in preclinical heart failure models. The consistent improvement observed across diverse EV sources, biomaterials, and animal models underscores the exciting potential of this synergistic approach.
Topics: Animals; Biocompatible Materials; Extracellular Vesicles; Mesenchymal Stem Cells; Heart Failure; Inflammation
PubMed: 37811703
DOI: 10.1002/adhm.202301980 -
Cytotherapy Jan 2024Exosome therapy for traumatic spinal cord injury (TSCI) is a current research hotspot, but its therapeutic effect and the best source of stem cells for exosomes are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AIMS
Exosome therapy for traumatic spinal cord injury (TSCI) is a current research hotspot, but its therapeutic effect and the best source of stem cells for exosomes are unclear.
METHODS
The Web of Science, PubMed, Embase, Cochrane, and Scopus databases were searched from inception to March 28, 2023. Literature screening, data extraction and risk of bias assessment were performed independently by two investigators.
RESULTS
A total of 40 studies were included for data analysis. The findings of our traditional meta-analysis indicate that exosomes derived from stem cells significantly improve the motor function of TSCI at various time points (1 week: weighted mean difference [WMD] = 1.58, 95% confidence interval [CI] 0.87-2.30] 2 weeks: WMD = 3.12, 95% CI 2.64-3.61; 3 weeks: WMD = 4.44, 95% CI 3.27-5.60; 4 weeks: WMD = 4.54, 95% CI 3.42-5.66). Four kinds of stem cell-derived exosomes have been studied: bone marrow mesenchymal stem cells, adipose mesenchymal stem cells, umbilical cord mesenchymal stem cells and neural stem cells. The results of the network meta-analysis showed that there was no significant statistical difference in the therapeutic effect among the exosomes derived from four kinds of stem cells at different treatment time points. Although exosomes derived from bone marrow mesenchymal stem cells are the current research focus, exosomes derived from neural stem cells have the most therapeutic potential and should become the focus of future attention.
CONCLUSIONS
The exosomes derived from stem cells can significantly improve the motor function of TSCI rats, and the exosomes derived from neural stem cells have the most therapeutic potential. However, the lower evidence quality of animal studies limits the reliability of experimental results, emphasizing the need for more high-quality, direct comparative studies to explore the therapeutic efficacy of exosomes and the best source of stem cells.
Topics: Rats; Animals; Exosomes; Network Meta-Analysis; Reproducibility of Results; Spinal Cord Injuries; Mesenchymal Stem Cells; Spinal Cord
PubMed: 37804282
DOI: 10.1016/j.jcyt.2023.09.002 -
BMC Cancer Oct 2023Extracellular vesicles (EVs) hold promise for improving our understanding of radiotherapy response in glioblastoma due to their role in intercellular communication...
Shooting the messenger: a systematic review investigating extracellular vesicle isolation and characterisation methods and their influence on understanding extracellular vesicles-radiotherapy interactions in glioblastoma.
BACKGROUND
Extracellular vesicles (EVs) hold promise for improving our understanding of radiotherapy response in glioblastoma due to their role in intercellular communication within the tumour microenvironment (TME). However, methodologies to study EVs are evolving with significant variation within the EV research community.
METHODS
We conducted a systematic review to critically appraise EV isolation and characterisation methodologies and how this influences our understanding of the findings from studies investigating radiotherapy and EV interactions in glioblastoma. 246 articles published up to 24/07/2023 from PubMed and Web of Science were identified using search parameters related to radiotherapy, EVs, and glioblastoma. Two reviewers evaluated study eligibility and abstracted data.
RESULTS
In 26 articles eligible for inclusion (16 investigating the effects of radiotherapy on EVs, five investigating the effect of EVs on radiation response, and five clinical studies), significant heterogeneity and frequent omission of key characterisation steps was identified, reducing confidence that the results are related to EVs and their cargo as opposed to co-isolated bioactive molecules. However, the results are able to clearly identify interactions between EVs and radiotherapy bi-directionally within different cell types within the glioblastoma TME. These interactions facilitate transferable radioresistance and oncogenic signalling, highlighting that EVs are an important component in the variability of glioblastoma radiotherapy response.
CONCLUSIONS
Future multi-directional investigations interrogating the whole TME are required to improve subsequent clinical translation, and all studies should incorporate up to date controls and reporting requirements to increase the validity of their findings. This would be facilitated by increased collaboration between less experienced and more experienced EV research groups.
Topics: Humans; Glioblastoma; Signal Transduction; Cell Communication; Extracellular Vesicles; Tumor Microenvironment
PubMed: 37798728
DOI: 10.1186/s12885-023-11437-6 -
Frontiers in Molecular Neuroscience 2023Knowledge on the human gut microbiota in health and disease continues to rapidly expand. In recent years, changes in the gut microbiota composition have been reported as...
INTRODUCTION
Knowledge on the human gut microbiota in health and disease continues to rapidly expand. In recent years, changes in the gut microbiota composition have been reported as a part of the pathology in numerous neurodegenerative diseases. Bacterial extracellular vesicles (EVs) have been suggested as a novel mechanism for the crosstalk between the brain and gut microbiota, physiologically connecting the observed changes in the brain to gut microbiota dysbiosis.
METHODS
Publications reporting findings on bacterial EVs passage through the blood-brain barrier were identified in PubMed and Scopus databases.
RESULTS
The literature search yielded 138 non-duplicate publications, from which 113 records were excluded in title and abstract screening step. From 25 publications subjected to full-text screening, 8 were excluded. The resulting 17 publications were considered for the review.
DISCUSSION
Bacterial EVs have been described with capability to cross the blood-brain barrier, but the mechanisms behind the crossing remain largely unknown. Importantly, very little data exists in this context on EVs secreted by the human gut microbiota. This systematic review summarizes the present evidence of bacterial EVs crossing the blood-brain barrier and highlights the importance of future research on gut microbiota-derived EVs in the context of gut-brain communication across the blood-brain barrier.
PubMed: 37781094
DOI: 10.3389/fnmol.2023.1227655 -
Biomedicines Aug 2023Mesenchymal stem cells (MSCs) have demonstrated potential in both clinical and pre-clinical research for mitigating tissue damage and inflammation associated with acute... (Review)
Review
Mesenchymal stem cells (MSCs) have demonstrated potential in both clinical and pre-clinical research for mitigating tissue damage and inflammation associated with acute pancreatitis (AP) via paracrine mechanisms. Hence, there has been a recent surge of interest among researchers in utilizing MSC cultured medium (CM) and its components for the treatment of AP, which is recognized as the primary cause of hospitalization for gastrointestinal disorders globally. A systematic review was conducted by searching the MEDLINE, EMBASE, and Web of Science databases. Studies that involve the administration of MSC-CM, extracellular vesicles/microvesicles (EVs/MVs), or exosomes to AP animal models are included. A total of six research studies, including eight experiments, were identified as relevant. The findings of this study provide evidence in favor of a beneficial impact of MSC-CM on both clinical and immunological outcomes. Nevertheless, prior to clinical trials, large animal models should be used and prolonged observation periods conducted in pre-clinical research. Challenges arise due to the lack of standardization and consensus on isolation processes, quantifications, and purity testing, making it difficult to compare reports and conduct meta-analyses in MSC-CM-based therapies.
PubMed: 37760784
DOI: 10.3390/biomedicines11092343 -
Cell Journal Sep 2023The secretome of stem cells consists of a spectrum of bioactive factors secreted by stem cells grown in culture mediacytokines, chemokines, and growth factors in...
The secretome of stem cells consists of a spectrum of bioactive factors secreted by stem cells grown in culture mediacytokines, chemokines, and growth factors in addition to extracellular vesicles (exosomes and microvesicles). Ease of handling and storage of secretomes along with their bioactivity towards processes in skin aging and customizability makes them an appealing prospective therapy for skin aging. This systematic review aims to investigate the potential usage of ascorbic acid (AA)-supplemented stem cell secretomes (SCS) in managing skin aging. We extracted articles from three databases: PubMed, Scopus, and Cochrane. This review includes , and clinical studies published in English that discuss the correlation of AA-supplemented-SCS with skin aging. We identified 1111 articles from database and non-database sources from which nine studies met the inclusion criteria. However, the study results were less specific due to the limited amount of available research that specifically assessed the effects of AAsupplemented SCS in skin aging. Although further studies are necessary, the AA modification of SCS is a promising potential for improving skin health.
PubMed: 37718762
DOI: 10.22074/cellj.2023.1995999.1253 -
Stem Cells Translational Medicine Dec 2023The development of extracellular vesicles (EVs) therapies has revolutionized personalized medicine, opening up new possibilities for treatment. EVs have emerged as a...
The development of extracellular vesicles (EVs) therapies has revolutionized personalized medicine, opening up new possibilities for treatment. EVs have emerged as a promising therapeutic tool within this field due to their crucial role in intercellular communication across various cell types and organisms. This systematic review aims to evaluate the therapeutic potential of oral mesenchymal stem cell (MSC)-derived EVs for bone regeneration, specifically focusing on findings from preclinical models. Sixteen articles meeting the inclusion criteria were selected following document analysis. The biological effects of oral MSC-derived EVs predominantly involve the upregulation of proteins associated with angiogenesis, and inflammation resolution, alongside the downregulation of proinflammatory cytokines. Moreover, these therapeutic agents have been found to contain a significant quantity of different molecules (proteins, lipids, DNA, microRNAs, etc) further contributing to their modulatory potential. The findings from this systematic review underscore that oral MSC-derived EVs, irrespective of their specific population, have the ability to enhance the osteogenic repair response in maxillary bone or periodontal defects. In summary, this systematic review highlights the promising potential of oral MSC-derived EVs for bone regeneration based on evidence from preclinical models. The comprehensive assessment of their biological effects and the presence of microRNAs underscores their therapeutic significance. These findings support the utilization of oral MSC-derived EVs in enhancing the osteogenic repair response in various maxillary bone or periodontal defects, providing insights into the mechanisms involved and potential therapeutic applications in the field of personalized medicine.
Topics: Mesenchymal Stem Cells; Extracellular Vesicles; MicroRNAs; Bone Regeneration; Osteogenesis
PubMed: 37715961
DOI: 10.1093/stcltm/szad059