scholarly journals The Potential Use of Mesenchymal Stem Cells and Their Derived Exosomes as Immunomodulatory Agents for COVID-19 Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Faisal A. Alzahrani ◽  
Islam M. Saadeldin ◽  
Abrar Ahmad ◽  
Dipak Kumar ◽  
Esam I. Azhar ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
World Health ◽  
Inhalation Therapy ◽  
Great Promise ◽  
Allogenic Bone ◽  
Lung Injuries ◽  
Health Organization

A novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) causing lethal acute respiratory disease emerged in December 2019. The World Health Organization named this disease “COVID-19” and declared it a pandemic on March 11, 2020. Many studies have shown that mesenchymal stem cells (MSCs) and their exosomes (MSCs-Exo), which are isolated from allogenic bone marrow stem cells, significantly lower the risk of alveolar inflammation and other pathological conditions associated with distinct lung injuries. For example, in acute respiratory distress syndrome (ARDS) and pneumonia patients, MSCs-Exo and MSCs provide similar healing properties and some clinical trials have used cell-based inhalation therapy which show great promise. MSCs and MSCs-Exo have shown potential in clinical trials as a therapeutic tool for severely affected COVID-19 patients when compared to other cell-based therapies, which may face challenges like the cells’ sticking to the respiratory tract epithelia during administration. However, the use of MSCs or MSCs-Exo for treating COVID-19 should strictly adhere to the appropriate manufacturing practices, quality control measurements, preclinical safety and efficacy data, and the proper ethical regulations. This review highlights the available clinical trials that support the therapeutic potential of MSCs or MSCs-Exo in severely affected COVID-19 patients.

From mesenchymal stem cells and stromal cells - from bench to bedside

2019 ◽  
Vol 1 (1) ◽  
pp. 36-39
Author(s):  
Bernd Giebel ◽  
Verena Börger ◽  
Mario Gimona ◽  
Eva Rohde
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Stromal Cells ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Cell Replacement ◽  
Beneficial Effects ◽  
Promising Tool

Human mesenchymal stem/stromal cells (MSCs) represent a promising tool in regenerative medicine. Until now, almost one thousand NIH-registered clinical trials investigated their immunomodulatory and pro-regenerative therapeutic potential in various diseases. Despite controversial reports regarding the efficacy of MSC-treatments, MSCs appear to exert their beneficial effects in a paracrine manner rather than by cell replacement. In this context, extracellular vesicles (EVs), such as exosomes and microvesicles, seem to induce the MSCs’ therapeutic effects. Here, we briefly illustrate the potential of MSC-EVs as therapeutic agent of the future.

scholarly journals Challenges and advances in clinical applications of mesenchymal stromal cells

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tian Zhou ◽  
Zenan Yuan ◽  
Jianyu Weng ◽  
Duanqing Pei ◽  
Xin Du ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Clinical Applications ◽  
Disease Models ◽  
Animal Disease ◽  
Animal Disease Models

AbstractMesenchymal stromal cells (MSCs), also known as mesenchymal stem cells, have been intensely investigated for clinical applications within the last decades. However, the majority of registered clinical trials applying MSC therapy for diverse human diseases have fallen short of expectations, despite the encouraging pre-clinical outcomes in varied animal disease models. This can be attributable to inconsistent criteria for MSCs identity across studies and their inherited heterogeneity. Nowadays, with the emergence of advanced biological techniques and substantial improvements in bio-engineered materials, strategies have been developed to overcome clinical challenges in MSC application. Here in this review, we will discuss the major challenges of MSC therapies in clinical application, the factors impacting the diversity of MSCs, the potential approaches that modify MSC products with the highest therapeutic potential, and finally the usage of MSCs for COVID-19 pandemic disease.

scholarly journals Updates on clinical trials evaluating the regenerative potential of allogenic mesenchymal stem cells in COVID-19

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Dhavan Sharma ◽  
Feng Zhao
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Adaptive Immune Response ◽  
Standard Of Care ◽  
Multiple Organ ◽  
Current Standard ◽  
Number Of Patients ◽  
Standard Of Care Treatment

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected nearly 118 million people and caused ~2.6 million deaths worldwide by early 2021, during the coronavirus disease 2019 (COVID-19) pandemic. Although the majority of infected patients show mild-to-moderate symptoms, a small fraction of patients develops severe symptoms. Uncontrolled cytokine production and the lack of substantive adaptive immune response result in hypoxia, acute respiratory distress syndrome (ARDS), or multiple organ failure in severe COVID-19 patients. Since the current standard of care treatment is insufficient to alleviate severe COVID-19 symptoms, many clinics have been prompted to perform clinical trials involving the infusion of mesenchymal stem cells (MSCs) due to their immunomodulatory and therapeutic properties. Several phases I/II clinical trials involving the infusion of allogenic MSCs have been performed last year. The focus of this review is to critically evaluate the safety and efficacy outcomes of the most recent, placebo-controlled phase I/II clinical studies that enrolled a larger number of patients, in order to provide a statistically relevant and comprehensive understanding of MSC’s therapeutic potential in severe COVID-19 patients. Clinical outcomes obtained from these studies clearly indicate that: (i) allogenic MSC infusion in COVID-19 patients with ARDS is safe and effective enough to decreases a set of inflammatory cytokines that may drive COVID-19 associated cytokine storm, and (ii) MSC infusion efficiently improves COVID-19 patient survival and reduces recovery time. These findings strongly support further investigation into MSC-infusion in larger clinical trials for COVID-19 patients with ARDS, who currently have a nearly 50% of mortality rate.

scholarly journals Downregulation of MicroRNA-206 Alleviates the Sublethal Oxidative Stress-Induced Premature Senescence and Dysfunction in Mesenchymal Stem Cells via Targeting Alpl

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Xuan Liu ◽  
Ziying Yang ◽  
Qingyou Meng ◽  
Yueqiu Chen ◽  
Lianbo Shao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Underlying Mechanism ◽  
Great Promise ◽  
Premature Senescence ◽  
Regenerative Capacity ◽  
Cell Functions ◽  
Stress Induced Premature Senescence

Bone marrow-derived mesenchymal stem cells (MSCs) have shown great promise in tissue engineering and regenerative medicine; however, the regenerative capacity of senescent MSCs is greatly reduced, thus exhibiting limited therapy potential. Previous studies uncovered that microRNA-206 (miR-206) could largely regulate cell functions, including cell proliferation, survival, and apoptosis, but whether miR-206 is involved in the senescent process of MSCs remains unknown. In this study, we mainly elucidated the effects of miR-206 on MSC senescence and the underlying mechanism. We discovered that miR-206 was upregulated in the senescent MSCs induced by H2O2, and abrogation of miR-206 could alleviate this tendency. Besides, we determined that by targeting Alpl, miR-206 could ameliorate the impaired migration and paracrine function in MSCs reduced by H2O2. In vivo study, we revealed that inhibition of miR-206 in senescent MSCs could effectively protect their potential for myocardial infarction treatment in a rat MI model. In summary, we examined that inhibition of miR-206 in MSCs can alleviate H2O2-induced senescence and dysfunction, thus protecting its therapeutic potential.

scholarly journals THE THERAPEUTIC POTENTIAL OF IVERMECTIN FOR COVID-19: A SYSTEMATIC REVIEW OF MECHANISMS AND EVIDENCE

2020 ◽  
Author(s):  
Stefanie Kalfas ◽  
Kumar Visvanathan ◽  
Kim Chan ◽  
John Drago
Keyword(s):  
Clinical Trials ◽  
Therapeutic Potential ◽  
Safety Data ◽  
Clinical Severity ◽  
World Health ◽  
Study Results ◽  
Immunomodulatory Action ◽  
Health Organization ◽  
Clinical Trials Registry

ABSTRACTIntroductionIvermectin is a commonly used antihelminthic agent with over 35 years of established safety data in humans. Recent data demonstrates antiviral activity in vitro against SARS-CoV-2, in addition to a range of viruses. In vitro and animal models also provide evidence of immunomodulatory action. These additional modes of action are supported by in silico modelling, which propose a number of viral and host targets that would mediate these effects.ObjectivesThe aim of this study is to systematically review the published and preprint clinical literature and study results that assessed the potential role of ivermectin as a COVID-19 therapeutic and prophylactic agent.MethodsWe conducted a comprehensive review of PubMed, medRxiv, ClinicalTrials.gov, Global Coronavirus COVID-19 Clinical Trial Tracker, World Health Organization International Clinical Trials Registry Platform, EU Clinical Trials Register, ANZ clinical trials registry, and references from relevant articles.ResultsSearch keywords- “COVID-19 (and synonyms) AND ivermectin”- generated 86 articles on PubMed, 48 on medRvix and 37 on clinicaltrials.gov at the time of writing. Twelve of these were listed as completed clinical trials and of these, 8 were included as investigators had released results. Positive mortality benefit, reduced time to clinical recovery, reduced incidence of disease progression and decreased duration of hospital admission were reported in patients across all stages of clinical severity.LimitationsDue to the time-critical nature of the COVID-19 pandemic our review included preprint data, which must be interpreted with caution while it awaits peer review.

scholarly journals Mesenchymal Stem Cells as Therapeutic Agents and Novel Carriers for the Delivery of Candidate Genes in Acute Kidney Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yuxiang Liu ◽  
Jingai Fang
Keyword(s):  
Stem Cells ◽  
Acute Kidney Injury ◽  
Mesenchymal Stem Cells ◽  
Genetic Modification ◽  
Therapeutic Potential ◽  
Kidney Injury ◽  
Tubular Epithelial Cell ◽  
Great Promise ◽  
Pharmaceutical Treatment ◽  
Therapeutic Outcomes

Acute kidney injury (AKI) is a heterogeneous syndrome characterized by a dramatic increase in serum creatinine. Mild AKI may merely be confined to kidney damage and resolve within days; however, severe AKI commonly involves extrarenal organ dysfunction and is associated with high mortality. There is no specific pharmaceutical treatment currently available that can reverse the course of this disease. Notably, mesenchymal stem cells (MSCs) show great promise for the management of AKI by targeting multiple pathophysiological pathways to facilitate tubular epithelial cell repair. It has been well established that the unique characteristics of MSCs make them ideal vectors for gene therapy. Thus, genetic modification has been attempted to achieve improved therapeutic outcomes in the management of AKI by overexpressing trophic cytokines or facilitating MSC delivery to renal tissues. The present article provides a comprehensive review of genetic modification strategies targeted at optimizing the therapeutic potential of MSCs in AKI.

scholarly journals Mesenchymal Stem Cells for Cardiac Regeneration: Translation to Bedside Reality

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Mohammad T. Elnakish ◽  
Fatemat Hassan ◽  
Duaa Dakhlallah ◽  
Clay B. Marsh ◽  
Ibrahim A. Alhaider ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Treatment Options ◽  
Cardiac Regeneration ◽  
World Health ◽  
Cardiovascular Research ◽  
Cell Based Therapy ◽  
Management Approaches ◽  
Health Organization

Cardiovascular disease (CVD) is the leading cause of death worldwide. According to the World Health Organization (WHO), an estimate of 17.3 million people died from CVDs in 2008 and by 2030, the number of deaths is estimated to reach almost 23.6 million. Despite the development of a variety of treatment options, heart failure management has failed to inhibit myocardial scar formation and replace the lost cardiomyocyte mass with new functional contractile cells. This shortage is complicated by the limited ability of the heart for self-regeneration. Accordingly, novel management approaches have been introduced into the field of cardiovascular research, leading to the evolution of gene- and cell-based therapies. Stem cell-based therapy (aka, cardiomyoplasty) is a rapidly growing alternative for regenerating the damaged myocardium and attenuating ischemic heart disease. However, the optimal cell type to achieve this goal has not been established yet, even after a decade of cardiovascular stem cell research. Mesenchymal stem cells (MSCs) in particular have been extensively investigated as a potential therapeutic approach for cardiac regeneration, due to their distinctive characteristics. In this paper, we focus on the therapeutic applications of MSCs and their transition from the experimental benchside to the clinical bedside.

Addressing the importance of Stem cell-based therapy: a Perspective in the treatment of COVID-19’

2020 ◽  
Vol 20 ◽  
Author(s):  
Christine Ibrahim ◽  
Hanna Semaan ◽  
Marwan El-Sabban ◽  
Fadia Najjar ◽  
Aline Hamade
Keyword(s):  
Stem Cell ◽  
Drug Repositioning ◽  
World Health ◽  
Unknown Etiology ◽  
Cell Based Therapy ◽  
Pathogenic Virus ◽  
Lung Injuries ◽  
Healthcare Crisis ◽  
Health Organization ◽  
Potential Use

: Severe acute respiratory syndrome-associated corona virus 2 (SARS-CoV-2), is an extremely pathogenic virus belonging to the family of Coronaviridae. First identified in Wuhan China in December 2019 after an epidemiological investigation of an emerging cluster of pneumonia of unknown etiology, SARS-CoV-2 was declared the cause of a pandemic on March 11 by the World Health Organization (WHO) pointing to the over 118000 cases of Coronavirus disease 2019 (COVID- 19) in over 110 countries. Despite the promising results of drug repositioning studies in the treatment of COVID-19, the evidence of their safety and efficacy remains inconclusive. Cell based therapy has been proven safe and possibly effective in treating multiple lung injuries and diseases but its potential use in the treatment of COVID-19 has not been yet elucidated. Our aim in this review is to provide an overview on the immunomodulatory effect and the regenerative capacity of stem cells and their secretome in the treatment of many diseases including lung injuries. Those findings may contribute to a better understanding of the potential of stem cell therapy in SARS-CoV-2 infection and its potential use in order to find a solution for this healthcare crisis.

Therapeutic Potential of Amniotic Fluid Derived Mesenchymal Stem Cells Based on their Differentiation Capacity and Immunomodulatory Properties

2019 ◽  
Vol 14 (4) ◽  
pp. 327-336 ◽  
Author(s):  
Carl R. Harrell ◽  
Marina Gazdic ◽  
Crissy Fellabaum ◽  
Nemanja Jovicic ◽  
Valentin Djonov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Animal Models ◽  
Amniotic Fluid ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Therapeutic Effects ◽  
Differentiation Potential ◽  
Differentiation Capacity ◽  
Cell Based Therapy

Background: Amniotic Fluid Derived Mesenchymal Stem Cells (AF-MSCs) are adult, fibroblast- like, self-renewable, multipotent stem cells. During the last decade, the therapeutic potential of AF-MSCs, based on their huge differentiation capacity and immunomodulatory characteristics, has been extensively explored in animal models of degenerative and inflammatory diseases. Objective: In order to describe molecular mechanisms responsible for the therapeutic effects of AFMSCs, we summarized current knowledge about phenotype, differentiation potential and immunosuppressive properties of AF-MSCs. Methods: An extensive literature review was carried out in March 2018 across several databases (MEDLINE, EMBASE, Google Scholar), from 1990 to present. Keywords used in the selection were: “amniotic fluid derived mesenchymal stem cells”, “cell-therapy”, “degenerative diseases”, “inflammatory diseases”, “regeneration”, “immunosuppression”. Studies that emphasized molecular and cellular mechanisms responsible for AF-MSC-based therapy were analyzed in this review. Results: AF-MSCs have huge differentiation and immunosuppressive potential. AF-MSCs are capable of generating cells of mesodermal origin (chondrocytes, osteocytes and adipocytes), neural cells, hepatocytes, alveolar epithelial cells, insulin-producing cells, cardiomyocytes and germ cells. AF-MSCs, in juxtacrine or paracrine manner, regulate proliferation, activation and effector function of immune cells. Due to their huge differentiation capacity and immunosuppressive characteristic, transplantation of AFMSCs showed beneficent effects in animal models of degenerative and inflammatory diseases of nervous, respiratory, urogenital, cardiovascular and gastrointestinal system. Conclusion: Considering the fact that amniotic fluid is obtained through routine prenatal diagnosis, with minimal invasive procedure and without ethical concerns, AF-MSCs represents a valuable source for cell-based therapy of organ-specific or systemic degenerative and inflammatory diseases.

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