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Journal of Translational Medicine Apr 2023Multiple preclinical studies have reported a beneficial effect of extracellular vesicles (EVs), especially mesenchymal stem cells derived EVs (MSC-EVs), in the treatment... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple preclinical studies have reported a beneficial effect of extracellular vesicles (EVs), especially mesenchymal stem cells derived EVs (MSC-EVs), in the treatment of sepsis. However, the therapeutic effect of EVs is still not universally recognized. Therefore, we conducted this meta-analysis by summarizing data from all published studies that met certain criteria to systematically review the association between EVs treatment and mortality in animal models of sepsis.
METHODS
Systematic retrieval of all studies in PubMed, Cochrane and Web of Science that reported the effects of EVs on sepsis models up to September 2022. The primary outcome was animal mortality. After screening the eligible articles according to inclusion and exclusion criteria, the inverse variance method of fixed effect model was used to calculate the joint odds ratio (OR) and 95% confidence interval (CI). Meta-analysis was performed by RevMan version 5.4.
RESULTS
In total, 17 studies met the inclusion criteria. Meta-analysis of those studies showed that EVs treatment was associated with reduced mortality in animal models of sepsis (OR 0.17 95% CI: 0.11,0.26, P < 0.001). Further subgroup analysis showed that the mode of sepsis induction, the source, dose, time and method of injection, and the species and gender of mice had no significant effect on the therapeutic effect of EVs.
CONCLUSION
This meta-analysis showed that MSC-EVs treatment may be associated with lower mortality in animal models of sepsis. Subsequent preclinical studies will need to address the standardization of dose, source, and timing of EVs to provide comparable data. In addition, the effectiveness of EVs in treating sepsis must be studied in large animal studies to provide important clues for human clinical trials.
Topics: Mice; Humans; Animals; Disease Models, Animal; Extracellular Vesicles; Mesenchymal Stem Cells; Sepsis; Cell- and Tissue-Based Therapy
PubMed: 37069645
DOI: 10.1186/s12967-023-04121-7 -
Journal of Clinical Medicine Nov 2019Secretome and extracellular vesicles (EVs) are considered a promising option to exploit mesenchymal stem cells' (MSCs) properties to address knee osteoarthritis (OA).... (Review)
Review
Secretome and extracellular vesicles (EVs) are considered a promising option to exploit mesenchymal stem cells' (MSCs) properties to address knee osteoarthritis (OA). The aim of this systematic review was to analyze both the in vitro and in vivo literature, in order to understand the potential of secretome and EVs as a minimally invasive injective biological approach. A systematic review of the literature was performed on PubMed, Embase, and Web of Science databases up to 31 August 2019. Twenty studies were analyzed; nine in vitro, nine in vitro and in vivo, and two in vivo. The analysis showed an increasing interest in this emerging field, with overall positive findings. Promising in vitro results were documented in terms of enhanced cell proliferation, reduction of inflammation, and down-regulation of catabolic pathways while promoting anabolic processes. The positive in vitro findings were confirmed in vivo, with studies showing positive effects on cartilage, subchondral bone, and synovial tissues in both OA and osteochondral models. However, several aspects remain to be clarified, such as the different effects induced by EVs and secretome, which is the most suitable cell source and production protocol, and the identification of patients who may benefit more from this new biological approach for knee OA treatment.
PubMed: 31689923
DOI: 10.3390/jcm8111867 -
Experimental Hematology & Oncology Feb 2021Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of non-Hodgkin's lymphomas (NHL). DLBCL is an aggressive malignancy that displays a great... (Review)
Review
Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of non-Hodgkin's lymphomas (NHL). DLBCL is an aggressive malignancy that displays a great heterogeneity in terms of morphology, genetics and biological behavior. While a sustained complete remission is obtained in the majority of patients with standard immunochemotherapy, patients with refractory of relapsed disease after first-line treatment have a poor prognosis. This patient group represents an important unmet need in lymphoma treatment. In recent years, improved understanding of the underlying molecular pathogenesis had led to new classification and prognostication tools, including the development of cell-free biomarkers in liquid biopsies. Although the majority of studies have focused on the use of cell-free fragments of DNA (cfDNA), there has been an increased interest in circulating-free coding and non-coding RNA, including messenger RNA (mRNA), microRNA (miRNA), long non-coding RNA (lncRNA) and circular RNA (circRNA), as well as RNA encapsulated in extracellular vesicles or tumor-educated platelets (TEPs). We performed a systematic search in PubMed to identify articles that evaluated circulating RNA as diagnostic, subtype, treatment response or prognostic biomarkers in a human DLBCL population. A total of 35 articles met the inclusion criteria. The aim of this systematic review is to present the current understanding of circulating RNA molecules as biomarker in DLBCL and to discuss their future potential.
PubMed: 33593440
DOI: 10.1186/s40164-021-00208-3 -
Life (Basel, Switzerland) Jul 2021Myeloproliferative neoplasms (MPNs) are rare, clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid... (Review)
Review
Myeloproliferative neoplasms (MPNs) are rare, clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid cells is noted. Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are included in the category of Philadelphia-negative, so-called classical MPNs. The potential applications of liquid biopsy and liquid biopsy-based biomarkers have not been explored in MPNs until now. Thus, a systematic search was computed in PubMed/MEDLINE, Web of Science and The Cochrane Library and, in total, 198 potentially relevant papers were detected. Following the removal of duplicates ( = 85), 113 records were screened. After the exclusion of irrelevant manuscripts based on the screening of their titles and abstracts ( = 81), we examined the full texts of 33 manuscripts. Finally, after we applied the exclusion and inclusion criteria, 27 original articles were included in this review. Overall, the data analyzed in this review point out that liquid biopsy and liquid biopsy-based biomarkers (cell-free DNA, extracellular vesicles, microparticles, circulating endothelial cells) could be used in MPNs for diagnostic and prognostic purposes. Future research is needed to clarify whether this technique can be employed to differentiate between MPN subtypes and secondary causes of erythrocytosis, thrombocytosis and myelofibrosis, as well as to predict the development of thrombosis.
PubMed: 34357048
DOI: 10.3390/life11070677 -
Frontiers in Immunology 2021Breast milk is the primary source of nutrition and hydration for the newborn infant but also plays an important role in the child's first immune defense. Additionally,...
UNLABELLED
Breast milk is the primary source of nutrition and hydration for the newborn infant but also plays an important role in the child's first immune defense. Additionally, several breast milk factors have been implicated in immune-related health outcomes later in life, including immunoglobulins, cytokines, chemokines, growth factors and, more recently, non-coding RNA (ncRNA) species. In this systematic review, we provide a comprehensive summary of the current literature on endogenous ncRNAs found in human breast milk. Thirty (30) relevant studies were identified and, whilst the majority studies focused on microRNAs (miRNAs), there is evidence that breast milk contains high quantities of RNA which also include long-coding RNAs, circular RNAs, as well as other short RNAs and fragmented tRNA and rRNAs. Among studies investigating miRNAs, miR-148a-3p, miR-30a/d-5p, miR-22-3p, miR-146b-5p, miR-200a/c-3p, and the 5p end of the let-7 miRNAs were commonly reported among the top 10 miRNAs in the cell, lipid, and skim milk fractions of breast milk. Methodological difference and small sample sizes limit the possibility of conclusively identifying which maternal and infant characteristics affect the miRNA profile. The highly expressed miRNAs were generally reported to be similar across lactational stage, milk fraction, maternal and infant characteristics, or infant growth and health. All the same, individual studies identify potential differences in miRNA expression levels which should be confirmed by future studies. Stability, uptake, and physiological functions of miRNAs were also considered in several studies. Breast milk miRNAs are relatively resistant to a range of harsh conditions and uptake experiments suggest that extracellular vesicles containing miRNAs and circular RNAs can be taken up by intestinal epithelial cells. Although the evidence regarding the functional effect of breast milk miRNAs is limited, the predicted functions range from metabolic and biosynthetic processes to signaling pathways, cellular adhesion, communication, growth, and differentiation. Finally, this systematic review highlights some of the methodological challenges and knowledge gaps which can help direct future research in this field. In particular, it is important to further investigate the bioavailability of miRNAs in different milk fractions, and to characterize other ncRNAs which are largely unstudied.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=138989, identifier CRD42020138989.
Topics: Exosomes; Extracellular Vesicles; Female; Humans; Lactation; MicroRNAs; Milk, Human; RNA, Untranslated
PubMed: 34539664
DOI: 10.3389/fimmu.2021.725323 -
Cureus Aug 2023Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer with several risk factors. Exosomes are extracellular vesicles generated by the fusion of... (Review)
Review
Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer with several risk factors. Exosomes are extracellular vesicles generated by the fusion of multivesicular structures with the cell membrane and play an important role as intercellular messengers. MicroRNA (miRNA) is a noncoding RNA and regulates post-transcriptional modification. The present systematic review aims to identify and correlate the possible association and role of circulating exosomes with OSCC. Using the search strategy, articles fulfilling the inclusion criteria, published between January 2012 to March 2022, were retrieved from online databases including PubMed, Scopus, Web of Science, and Cochrane Library. About 904 articles were found using an electronic database and a human search. After reviewing the titles and abstracts, 614 studies were eliminated, and duplicate articles were removed. Five studies were included in this systematic review. Circulating exosomal expression of miRNA27, miRNA 21, and miRNA 155 showed significant upregulation in OSCC patients. Circulating exosomes could be potential biomarkers to be used in the detection of patients with OSCC. More studies are warranted in this area to gain a better understanding of the pathophysiology of OSCC and the function of molecular markers from circulating exosomes. Understanding the role of molecular markers from circulating exosomes in pathogenesis will provide a better understanding of the development of the disease, necessitating more study in this area. According to this review, circulating exosomes might be a potential approach to the identification of OSCC.
PubMed: 37692575
DOI: 10.7759/cureus.43235 -
Stem Cells Translational Medicine Jul 2022Mesenchymal stromal cells (MSCs) may reduce mortality in patients with COVID-19; however, early evidence is based on few studies with marked interstudy heterogeneity.... (Meta-Analysis)
Meta-Analysis
Updated Living Systematic Review and Meta-analysis of Controlled Trials of Mesenchymal Stromal Cells to Treat COVID-19: A Framework for Accelerated Synthesis of Trial Evidence for Rapid Approval-FASTER Approval.
BACKGROUND
Mesenchymal stromal cells (MSCs) may reduce mortality in patients with COVID-19; however, early evidence is based on few studies with marked interstudy heterogeneity. The second iteration of our living systematic review and meta-analysis evaluates a framework needed for synthesizing evidence from high-quality studies to accelerate consideration for approval.
METHODS
A systematic search of the literature was conducted on November 15, 2021, to identify all English-language, full-text, and controlled clinical studies examining MSCs to treat COVID-19 (PROSPERO: CRD42021225431).
FINDINGS
Eleven studies were identified (403 patients with severe and/or critical COVID-19, including 207 given MSCs and 196 controls). All 11 studies reported mortality and were pooled through random-effects meta-analysis. MSCs decreased relative risk of death at study endpoint (RR: 0.50 [95% CI, 0.34-0.75]) and RR of death at 28 days after treatment (0.19 [95% CI], 0.05-0.78) compared to controls. MSCs also decreased length of hospital stay (mean difference (MD: -3.97 days [95% CI, -6.09 to -1.85], n = 5 studies) and increased oxygenation levels at study endpoint compared to controls (MD: 105.62 mmHg O2 [95% CI, 73.9-137.3,], n = 3 studies). Only 2 of 11 studies reported on all International Society for Cellular Therapy (ISCT) criteria for MSC characterization. Included randomized controlled trials were found to have some concerns (n = 2) to low (n = 4) risk of bias (RoB), while all non-randomized studies were found to have moderate (n = 5) RoB.
INTERPRETATION
Our updated living systematic review concludes that MSCs can likely reduce mortality in patients with severe or critical COVID-19. A master protocol based on our Faster Approval framework appears necessary to facilitate the more accelerated accumulation of high-quality evidence that would reduce RoB, improve consistency in product characterization, and standardize outcome reporting.
Topics: Bias; COVID-19; Humans; Lung; Mesenchymal Stem Cells; Randomized Controlled Trials as Topic
PubMed: 35758400
DOI: 10.1093/stcltm/szac038 -
Tissue Engineering and Regenerative... Feb 2022Increasing evidence suggests that stem cells or stem cell-derived cells may contribute to tissue repair, not only by replacing lost tissue but also by delivering complex... (Review)
Review
Increasing evidence suggests that stem cells or stem cell-derived cells may contribute to tissue repair, not only by replacing lost tissue but also by delivering complex sets of secretory molecules, called secretomes, into host injured tissues. In recent years, extracellular vesicles (EVs) have gained much attention for their diverse and important roles in a wide range of pathophysiological processes. EVs are released from most types of cells and mediates cell-cell communication by activating receptors on target cells or by being taken up by recipient cells. EVs, including microvesicles and exosomes, encapsulate and carry proteins, nucleic acids, and lipids in the lumen and on the cell surface. Thus, EV-mediated intercellular communication has been extensively studied across various biological processes. While a number of investigations has been conducted in different tissues and body fluids, the field lacks a systematic review on stem cell-derived EVs, especially regarding their roles in stemness and differentiation. Here, we provide an overview of the pathophysiological roles of EVs and summarize recent findings focusing on EVs released from various types of stem cells. We also highlight emerging evidence for the potential implication of EVs in self-renewal, differentiation, and reprograming and discuss the benefits and limitations in translational approaches.
Topics: Cell Communication; Exosomes; Extracellular Vesicles; Secretome; Stem Cells
PubMed: 34817808
DOI: 10.1007/s13770-021-00406-4 -
International Journal of Molecular... Sep 2022Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder, characterized by the misfolding and aggregation of α-synuclein (α-syn) into Lewy bodies... (Review)
Review
Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder, characterized by the misfolding and aggregation of α-synuclein (α-syn) into Lewy bodies and the degeneration of dopaminergic neurons in the substantia nigra pars compacta. The urge for an early diagnosis biomarker comes from the fact that clinical manifestations of PD are estimated to appear once the substantia nigra has deteriorated and there has been a reduction of the dopamine levels from the striatum. Nowadays, extracellular vesicles (EVs) play an important role in the pathogenesis of neuro-degenerative diseases as PD. A systematic review dated August 2022 was carried out with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses with the aim to analyze the potential role of EVs as biomarkers for PD. From a total of 610 articles retrieved, 29 were eligible. This review discusses the role of EVs biochemistry and their cargo proteins, such as α-syn and DJ-1 among others, detected by a proteomic analysis as well as miRNAs and lncRNAs, as potential biomarkers that can be used to create standardized protocols for early PD diagnosis as well as to evaluate disease severity and progression.
Topics: Biomarkers; Dopamine; Dopaminergic Neurons; Extracellular Vesicles; Humans; MicroRNAs; Parkinson Disease; Proteomics; RNA, Long Noncoding; alpha-Synuclein
PubMed: 36232833
DOI: 10.3390/ijms231911508 -
International Journal of Molecular... Apr 2022Despite the multidisciplinary management in the treatment of glioblastomas, the average survival of GBM patients is still 15 months. In recent years, molecular... (Review)
Review
Despite the multidisciplinary management in the treatment of glioblastomas, the average survival of GBM patients is still 15 months. In recent years, molecular biomarkers have gained more and more importance both in the diagnosis and therapy of glial tumors. At the same time, it has become clear that non neoplastic cells, which constitute about 30% of glioma mass, dramatically influence tumor growth, spread, and recurrence. This is the main reason why, in recent years, scientific research has been focused on understanding the function and the composition of tumor microenvironment and its role in gliomagenesis and recurrence. The aim of this review is to summarize the most recent discovery about resident microglia, tumor-associated macrophages, lymphocytes, and the role of extracellular vesicles and their bijective interaction with glioma cells. Moreover, we reported the most recent updates about new therapeutic strategies targeting immune system receptors and soluble factors. Understanding how glioma cells interact with non-neoplastic cells in tumor microenvironment is an essential step to comprehend mechanisms at the base of disease progression and to find new therapeutic strategies for GBM patients. However, no significant results have yet been obtained in studies targeting single molecules/pathways; considering the complex microenvironment, it is likely that only by using multiple therapeutic agents acting on multiple molecular targets can significant results be achieved.
Topics: Brain Neoplasms; Glioblastoma; Glioma; Humans; Macrophages; Microglia; Tumor Microenvironment
PubMed: 35456984
DOI: 10.3390/ijms23084166