scholarly journals The Therapeutic Effect of Extracellular Vesicles on Asthma in Pre-Clinical Models: A Systematic Review Protocol

2021 ◽  
Vol 1 (1) ◽  
pp. 84-95
Author(s):  
Patience O. Obi ◽  
Jennifer E. Kent ◽  
Maya M. Jeyaraman ◽  
Nicole Askin ◽  
Taiana M. Pierdoná ◽  
...  
Keyword(s):  
Systematic Review ◽  
Extracellular Vesicles ◽  
Current Knowledge ◽  
Grey Literature ◽  
Specific Treatment ◽  
Therapeutic Effects ◽  
Management Options ◽  
Paracrine Signalling

Asthma is the most common pediatric disease, characterized by chronic airway inflammation and airway hyperresponsiveness. There are several management options for asthma, but no specific treatment. Extracellular vesicles (EVs) are powerful cellular mediators of endocrine, autocrine and paracrine signalling, and can modulate biophysiological function in vitro and in vivo. A thorough investigation of therapeutic effects of EVs in asthma has not been conducted. Therefore, this systematic review is designed to synthesize recent literature on the therapeutic effects of EVs on physiological and biological outcomes of asthma in pre-clinical studies. An electronic search of Web of Science, EMBASE, MEDLINE, and Scopus will be conducted on manuscripts published in the last five years that adhere to standardized guidelines for EV research. Grey literature will also be included. Two reviewers will independently screen the selected studies for title and abstract, and full text based on the eligibility criteria. Data will be extracted, narratively synthesized and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review will summarize the current knowledge from preclinical studies investigating the therapeutic effects of EVs on asthma. The results will delineate whether EVs can mitigate biological hallmarks of asthma, and if so, describe the underlying mechanisms involved in the process. This insight is crucial for identifying key pathways that can be targeted to alleviate the burden of asthma. The data will also reveal the origin, dosage and biophysical characteristics of beneficial EVs. Overall, our results will provide a scaffold for future intervention and translational studies on asthma treatment.

scholarly journals Therapeutic Effects of Hypoxic and Pro-Inflammatory Priming of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Inflammatory Arthritis

2021 ◽  
Vol 23 (1) ◽  
pp. 126
Author(s):  
Alasdair G. Kay ◽  
Kane Treadwell ◽  
Paul Roach ◽  
Rebecca Morgan ◽  
Rhys Lodge ◽  
...  
Keyword(s):  
T Cell ◽  
Extracellular Vesicles ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Histopathological Analysis ◽  
Therapeutic Effects ◽  
Synovial Joint ◽  
Paracrine Signalling

Mesenchymal stem cells (MSCs) immunomodulate inflammatory responses through paracrine signalling, including via secretion of extracellular vesicles (EVs) in the cell secretome. We evaluated the therapeutic potential of MSCs-derived small EVs in an antigen-induced model of arthritis (AIA). EVs isolated from MSCs cultured normoxically (21% O2, 5% CO2), hypoxically (2% O2, 5% CO2) or with a pro-inflammatory cytokine cocktail were applied into the AIA model. Disease pathology was assessed post-arthritis induction through swelling and histopathological analysis of synovial joint structure. Activated CD4+ T cells from healthy mice were cultured with EVs or MSCs to assess deactivation capabilities prior to application of standard EVs in vivo to assess T cell polarisation within the immune response to AIA. All EVs treatments reduced knee-joint swelling whilst only normoxic and pro-inflammatory primed EVs improved histopathological outcomes. In vitro culture with EVs did not achieve T cell deactivation. Polarisation towards CD4+ helper cells expressing IL17a (Th17) was reduced when normoxic and hypoxic EV treatments were applied in vitro. Normoxic EVs applied into the AIA model reduced Th17 polarisation and improved Regulatory T cell (Treg):Th17 homeostatic balance. Normoxic EVs present the optimal strategy for broad therapeutic benefit. EVs present an effective novel technology with the potential for cell-free therapeutic translation.

scholarly journals THERAPEUTIC EFFECTS OF HYPOXIC AND PRO-INFLAMMATORY PRIMING OF MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES IN INFLAMMATORY ARTHRITIS

2021 ◽  
Author(s):  
Alasdair G Kay ◽  
Kane Treadwell ◽  
Paul Roach ◽  
Rebecca Morgan ◽  
Rhys Lodge ◽  
...  
Keyword(s):  
T Cell ◽  
Extracellular Vesicles ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Histopathological Analysis ◽  
Therapeutic Effects ◽  
Synovial Joint ◽  
Paracrine Signalling

Novel biological therapies have revolutionised the management of Rheumatoid Arthritis (RA) but no cure currently exists. Mesenchymal stem cells (MSCs) immunomodulate inflammatory responses through paracrine signalling, including via secretion of extracellular vesicles (EVs) in the cell secretome. We evaluated the therapeutic potential of MSCs-derived small EVs in an antigen-induced model of arthritis (AIA). EVs isolated from MSCs cultured normoxically (21% O2, 5% CO2), hypoxically (2% O2, 5% CO2) or with a pro-inflammatory cytokine cocktail were applied into the AIA model. Disease pathology was assessed post-arthritis induction through swelling and histopathological analysis of synovial joint structure. Activated CD4+ T cells from healthy mice were cultured with EVs or MSCs to assess deactivation capabilities prior to application of standard EVs in vivo to assess T cell polarisation within the immune response to AIA. All EVs treatments reduced knee-joint swelling whilst only normoxic and pro-inflammatory primed EVs improved histopathological outcomes. In vitro culture with EVs did not achieve T cell deactivation. Polarisation towards CD4+ helper cells expressing IL17a (Th17) was reduced when normoxic and hypoxic EV treatments were applied in vitro. Normoxic EVs applied into the AIA model reduced Th17 polarisation and improved Th17:Treg homeostatic balance. Priming of MSCs in EV production can be applied to alter the therapeutic efficacy however normoxic EVs present the optimal strategy for broad therapeutic benefit. The varied outcomes observed in MSCs priming may promote EVs optimised for therapies targeted for specific therapeutic priorities. EVs present an effective novel technology with potential for cell-free therapeutic translation.

A Systematic Review on Extracellular Vesicles-Enriched Fat Grafting: A Shifting Paradigm

2020 ◽  
Author(s):  
Mohammad Ghiasloo ◽  
Laura De Wilde ◽  
Kashika Singh ◽  
Patrick Tonnard ◽  
Alexis Verpaele ◽  
...  
Keyword(s):  
Systematic Review ◽  
Graft Survival ◽  
Extracellular Vesicles ◽  
Retention Rate ◽  
Fat Grafting ◽  
Retention Rates ◽  
Fat Graft ◽  
Cochrane Central Register

Abstract Background Recent evidence confirms that mesenchymal stem cells (MSCs) facilitate angiogenesis mainly through paracrine function. Extracellular vesicles (EVs) are regarded as key components of the cell secretome, possessing functional properties of their source cells. Subsequently, MSC-EVs have emerged as a novel cell-free approach to improve fat graft retention rate. Objectives To provide a systematic review of all studies reporting the use of MSC-EVs to improve graft retention rate. Methods A systematic search was undertaken using the Embase, PubMed and the Cochrane Central Register of Controlled Trials databases. Outcome measures included donor/receptor organism of the fat graft, study model, intervention groups, evaluation intervals, EV research data, in vitro and in vivo results. Results Of the total 1717 articles, 62 full-texts were screened. Seven studies reporting on 294mice were included. Overall, EV treated groups showed higher graft retention rates compared to untreated groups. Notably, retention rate was similar following EV- and MSC-treatment. In addition to reduced inflammation, graft enrichment with EVs resulted in early revascularization and better graft integrity. Interestingly, hypoxic preconditioning of MSCs improved their beneficial paracrine effects and led to a more proangiogenic EV population, as observed by both in vitro and in vivo results. Conclusions MSC-EVs appear to offer an interesting cell-free alternative to improve fat graft survival. While their clinical relevance remains to be determined, it is clear that not the cells, but their secretome is essential for graft survival. Thus, a paradigm shift from cell-assisted lipotransfer towards ‘secretome-assisted lipotransfer’ is well on its way.

scholarly journals Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2506
Author(s):  
Wamidh H. Talib ◽  
Ahmad Riyad Alsayed ◽  
Alaa Abuawad ◽  
Safa Daoud ◽  
Asma Ismail Mahmod
Keyword(s):  
Clinical Trials ◽  
Current Knowledge ◽  
Biological Activities ◽  
Experimental Studies ◽  
Therapeutic Effects ◽  
Cell Proliferation Inhibition ◽  
Different Types ◽  
Solid Foundation

Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy, and augmentation of the therapeutic effects of conventional anticancer therapies. Clinical trials revealed that melatonin is an effective adjuvant drug to all conventional therapies. This review summarized melatonin biosynthesis, availability from natural sources, metabolism, bioavailability, anticancer mechanisms of melatonin, its use in clinical trials, and pharmaceutical formulation. Studies discussed in this review will provide a solid foundation for researchers and physicians to design and develop new therapies to treat and prevent cancer using melatonin.

scholarly journals Management of STEC Gastroenteritis: Is There a Role for Probiotics?

2019 ◽  
Vol 16 (9) ◽  
pp. 1649 ◽  
Author(s):  
Mario Giordano ◽  
Maria Elisabetta Baldassarre ◽  
Viviana Palmieri ◽  
Diletta D. Torres ◽  
Vincenza Carbone ◽  
...  
Keyword(s):  
Immune Responses ◽  
Therapeutic Strategy ◽  
Current Knowledge ◽  
Specific Treatment ◽  
Probiotic Supplementation ◽  
Uremic Syndrome ◽  
Intestinal Functions ◽  
Gut Microorganisms

Shiga toxin-producing Escherichia Coli (STEC) infections routinely run as a common gastroenteritis, but in many cases they may evolve towards hemolytic uremic syndrome (HUS). HUS is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Gut microorganisms have a fundamental impact on human physiology, because they modulate normal intestinal functions and play a pivotal role in influencing the local and systemic immune responses. Despite surveillance established in many countries and major progresses in the understanding of STEC-HUS mechanisms, no specific treatment is currently available. Targeting the gut microbiota could represent a new potential therapeutic strategy in STEC infection. In this paper, we reviewed the current knowledge about microbiota characteristics of patients with STEC infections, as well as in vitro and in vivo evidence of probiotic supplementation in managing STEC gastroenteritis and in HUS onset prevention.

scholarly journals Adipose Mesenchymal Extracellular Vesicles as Alpha-1-Antitrypsin Physiological Delivery Systems for Lung Regeneration

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 965 ◽  
Author(s):  
Bari ◽  
Ferrarotti ◽  
Di Silvestre ◽  
Grisoli ◽  
Barzon ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Serum Starvation ◽  
Therapeutic Effects ◽  
Elastase Activity ◽  
Gene Encoding ◽  
Elastase Inhibitor ◽  
Proteomic Investigation ◽  
Alpha 1 Antitrypsin

Accumulating evidence shows that Mesenchymal Stem/Stromal Cells (MSCs) exert their therapeutic effects by the release of secretome, made of both soluble proteins and nano/microstructured extracellular vesicles (EVs). In this work, for the first time, we proved by a proteomic investigation that adipose-derived (AD)-MSC-secretome contains alpha-1-antitrypsin (AAT), the main elastase inhibitor in the lung, 72 other proteins involved in protease/antiprotease balance, and 46 proteins involved in the response to bacteria. By secretome fractionation, we proved that AAT is present both in the soluble fraction of secretome and aggregated and/or adsorbed on the surface of EVs, that can act as natural carriers promoting AAT in vivo stability and activity. To modulate secretome composition, AD-MSCs were cultured in different stimulating conditions, such as serum starvation or chemicals (IL-1β and/or dexamethasone) and the expression of the gene encoding for AAT was increased. By testing in vitro the anti-elastase activity of MSC-secretome, a dose-dependent effect was observed; chemical stimulation of AD-MSCs did not increase their secretome anti-elastase activity. Finally, MSC-secretome showed anti-bacterial activity on Gram-negative bacteria, especially for Klebsiella pneumoniae. These preliminary results, in addition to the already demonstrated immunomodulation, pave the way for the use of MSC-secretome in the treatment of AAT-deficiency lung diseases.

siRNA as a potential therapy for COVID-19

2021 ◽  
Vol 18 ◽  
Author(s):  
Ahmad Aljaberi ◽  
Eman M. Migdadi ◽  
Khalid M Abu Khadra ◽  
Mahmoud Abu Samak ◽  
Iman A Basheti ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Therapeutic Option ◽  
Target Selection ◽  
Genome Structure ◽  
Specific Treatment ◽  
Viral Escape ◽  
World Health ◽  
Corona Viruses

: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) is a highly contagious virus causing COVID-19 disease that severely impacted the world health, education, and economy systems in 2020. The numbers of infection cases and reported deaths are still increasing with no specific treatment identified yet to halt this pandemic. Currently, several proposed treatments are under preclinical and clinical investigations now, alongside the race to vaccinate to as much individuals as possible. The genome of SARS-CoV2 share similar gene organization as other viruses in the Coronaviridae family. It is a positive-sense, single-stranded RNA. This feature suggests that RNA interference (RNAi) is an attractive prophylactic and therapeutic option for the control of this pandemic and other possible future pandemics of the corona viruses. RNAi utilizes the use of siRNA molecules which are 21-29 nt duplexes RNA molecules that intervene with targeted gene expression in the cytoplasm by a specific mechanism of complementary destruction of mRNA. Previous experience with SARS-CoV and Middle East respiratory syndrome (MERS) showed that siRNA molecules were effective against these viruses in vitro and in vivo. Moreover, there have been extensive advances in siRNA technology in the past decade from chemistry and target selection considerations; which concluded with the successful approval of two commercial products based on siRNA technology. In addition, the current knowledge of the genome structure and functionality of the corona viruses enables the recognition of conserved sequences to optimize siRNA targeting and avoid viral escape through mutations, either for the current SARS-CoV2 as well as future corona viruses.

scholarly journals Effect of Mesenchymal Stem Cell-Derived Exosomes on Retinal Injury: A Review of Current Findings

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Raffaele Nuzzi ◽  
Paolo Caselgrandi ◽  
Alessandro Vercelli
Keyword(s):  
Current Knowledge ◽  
Target Cells ◽  
Therapeutic Effects ◽  
Retinal Damage ◽  
Phospholipid Membrane ◽  
Retinal Injury ◽  
Immunological Rejection ◽  
Reduction Effect

In recent years, various studies have followed in the literature on the therapeutic effects of mesenchymal stem cells (MSC) on damage in retinal cells. The evidence that MSCs exert their regenerative and damage reduction effect in a paracrine way, through the release of soluble factors and exosomes, is now consolidated. Exosomes are microvesicles formed by a double layer of phospholipid membrane and carry proteins and RNA, through which they play a therapeutic role on target cells. Scientific research has recently focused on the use of exosomes derived from MSC in various models of retinal damage in vitro and in vivo as they, compared to MSCs, have similar functions and at the same time have different advantages such as greater stability and handling, a lower chance of immunological rejection and no risk of malignant transformation. The purpose of this review is to summarize current knowledge on the therapeutic use of exosomes derived from MSCs in retinal damage and to stimulate new clinical perspectives regarding their use.

scholarly journals Seaweed Components as Potential Modulators of the Gut Microbiota

Marine Drugs ◽  
2021 ◽  
Vol 19 (7) ◽  
pp. 358
Author(s):  
Emer Shannon ◽  
Michael Conlon ◽  
Maria Hayes
Keyword(s):  
Gut Microbiota ◽  
Large Scale ◽  
Current Knowledge ◽  
Ex Vivo ◽  
Short Chain Fatty Acids ◽  
In Vivo Studies ◽  
Therapeutic Effects ◽  
Oral Bioaccessibility

Macroalgae, or seaweeds, are a rich source of components which may exert beneficial effects on the mammalian gut microbiota through the enhancement of bacterial diversity and abundance. An imbalance of gut bacteria has been linked to the development of disorders such as inflammatory bowel disease, immunodeficiency, hypertension, type-2-diabetes, obesity, and cancer. This review outlines current knowledge from in vitro and in vivo studies concerning the potential therapeutic application of seaweed-derived polysaccharides, polyphenols and peptides to modulate the gut microbiota through diet. Polysaccharides such as fucoidan, laminarin, alginate, ulvan and porphyran are unique to seaweeds. Several studies have shown their potential to act as prebiotics and to positively modulate the gut microbiota. Prebiotics enhance bacterial populations and often their production of short chain fatty acids, which are the energy source for gastrointestinal epithelial cells, provide protection against pathogens, influence immunomodulation, and induce apoptosis of colon cancer cells. The oral bioaccessibility and bioavailability of seaweed components is also discussed, including the advantages and limitations of static and dynamic in vitro gastrointestinal models versus ex vivo and in vivo methods. Seaweed bioactives show potential for use in prevention and, in some instances, treatment of human disease. However, it is also necessary to confirm these potential, therapeutic effects in large-scale clinical trials. Where possible, we have cited information concerning these trials.

scholarly journals Mesenchymal Stem Cell-Derived Extracellular Vesicles and Their Therapeutic Potential

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ashley G. Zhao ◽  
Kiran Shah ◽  
Brett Cromer ◽  
Huseyin Sumer
Keyword(s):  
Tissue Engineering ◽  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Target Cells ◽  
Therapeutic Effects ◽  
Multipotent Cells ◽  
Membrane Bound

Extracellular vesicles (EVs) are cell-derived membrane-bound nanoparticles, which act as shuttles, delivering a range of biomolecules to diverse target cells. They play an important role in maintenance of biophysiological homeostasis and cellular, physiological, and pathological processes. EVs have significant diagnostic and therapeutic potentials and have been studied both in vitro and in vivo in many fields. Mesenchymal stem cells (MSCs) are multipotent cells with many therapeutic applications and have also gained much attention as prolific producers of EVs. MSC-derived EVs are being explored as a therapeutic alternative to MSCs since they may have similar therapeutic effects but are cell-free. They have applications in regenerative medicine and tissue engineering and, most importantly, confer several advantages over cells such as lower immunogenicity, capacity to cross biological barriers, and less safety concerns. In this review, we introduce the biogenesis of EVs, including exosomes and microvesicles. We then turn more specifically to investigations of MSC-derived EVs. We highlight the great therapeutic potential of MSC-derived EVs and applications in regenerative medicine and tissue engineering.

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