Mesenchymal stem cells: current clinical progress in ARDS and COVID-19.
Ontology highlight
ABSTRACT:
SUBMITTER: Xiao K
PROVIDER: S-EPMC7373844 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:In late 2019, a novel coronavirus (SARS-CoV-2) emerged in Wuhan city, Hubei province, China. Rapidly escalated into a worldwide pandemic, it has caused an unprecedented and devastating situation on the global public health and society economy. The severity of recent coronavirus disease, abbreviated to COVID-19, seems to be mostly associated with the patients' immune response. In this vein, mesenchymal stromal/stem cells (MSCs) have been suggested as a worth-considering option against COVID-19 as their therapeutic properties are mainly displayed in immunomodulation and anti-inflammatory effects. Indeed, administration of MSCs can attenuate cytokine storm and enhance alveolar fluid clearance, endothelial recovery, and anti-fibrotic regeneration. Despite advantages attributed to MSCs application in lung injuries, there are still several issues __foremost probability of malignant transformation and incidence of MSCs-related coagulopathy__ which should be resolved for the successful application of MSC therapy in COVID-19. In the present study, we review the historical evidence of successful use of MSCs and MSC-derived extracellular vesicles (EVs) in the treatment of acute respiratory distress syndrome (ARDS). We also take a look at MSCs mechanisms of action in the treatment of viral infections, and then through studying both the dark and bright sides of this approach, we provide a thorough discussion if MSC therapy might be a promising therapeutic approach in COVID-19 patients.
| S-EPMC8079337 | biostudies-literature
Project description:The severe respiratory consequences of the coronavirus disease 2019 (COVID-19) pandemic have prompted the urgent need for novel therapies. Cell-based therapies, primarily using mesenchymal stromal cells (MSCs), have demonstrated safety and potential efficacy in the treatment of critical illness, particularly sepsis and acute respiratory distress syndrome (ARDS). However, there are limited preclinical data for MSCs in COVID-19. Recent studies have shown that MSCs could decrease inflammation, improve lung permeability, enhance microbe and alveolar fluid clearance, and promote lung epithelial and endothelial repair. In addition, MSC-based therapy has shown promising effects in preclinical studies and phase 1 clinical trials in sepsis and ARDS. Here, we review recent advances related to MSC-based therapy in the context of sepsis and ARDS and evaluate the potential value of MSCs as a therapeutic strategy for COVID-19.
| S-EPMC8517471 | biostudies-literature
Project description:Mesenchymal Stem Cells (MSCs), and Adipose-Derived Mesenchymal Stem Cells (AD-MSCs) have been used for many years in regenerative medicine for clinical and surgical applications. Additionally, recent studies reported improved respiratory activity after intravenous administration of MSCs into patients affected by coronavirus disease 2019 (COVID-19) caused by the Coronavirus 2 (SARS-CoV-2) suggesting their role as anti-viral therapy. Severe COVID-19 patients usually progress to acute respiratory distress syndrome, sepsis, metabolic acidosis that is difficult to correct, coagulation dysfunction, multiple organ failure, and even death in a short period after onset. Currently, there is still a lack of clinically effective drugs for such patients. The high secretory activity, the immune-modulatory effect, and the homing ability make MSCs and in particular AD-MSCs both a potential tool for the anti-viral drug-delivery in the virus microenvironment and potential cellular therapy. AD-MSCs as the most important exponent of MSCs are expected to reduce the risk of complications and death of patients due to their strong anti-inflammatory and immune-modulatory capabilities, which can improve microenvironment, promote neovascularization and enhance tissue repair capabilities. In this literature review, the role of regenerative strategies through MSCs, AD-MSCs, and adipocyte-secreted exosomal microRNAs (A-SE-miRs) as a potential antiviral therapy was reported, comparing the results found with current research progress on drugs and vaccines in COVID-19 disease.
| S-EPMC7505274 | biostudies-literature
Project description:At the end of 2019, novel coronavirus (COVID-19) infection was detected in Wuhan City, Hubei Province, China. The COVID-19 infection characteristics include a long incubation period, strong infectivity, and high fatality rate, and it negatively affects human health and social development. COVID-19 has become a common problem in the global medical and health system. It is essentially an acute self-limiting disease. Patients with severe COVID-19 infection usually progress to acute respiratory distress syndrome, sepsis, metabolic acidosis that is difficult to correct, coagulation dysfunction, multiple organ failure, and even death within a short period after onset. There remains a lack of effective drugs for such patients clinically. Mesenchymal stem cells (MSCs) are expected to reduce the risk of complications and death in patients because they have strong anti-inflammatory and immunomodulatory capabilities, which can improve the microenvironment, promote neovascularization, and enhance tissue repair capabilities. China is currently conducting several clinical trials on MSCs for the treatment of COVID-19. Here, we review the research progress related to using stem cells to treat patients with COVID-19.
| S-EPMC7522503 | biostudies-literature
Project description:Acute respiratory distress syndrome (ARDS) is the main cause for the COVID-19 infection-related morbidity and mortality. Recent clinical evidences suggest increased level of cytokines and chemokines targeting lung tissue as a prominent etiological factor. The immunomodulatory effect of mesenchymal stem cells (MSCs) as the alternative therapy for the treatment of inflammatory and autoimmune diseases is well known. Several studies have also revealed that similar therapeutic impacts of parent MSCs are also exhibited by MSCs-derived extracellular vesicles (EVs) including exosomes. In this review, we explored the therapeutic potential of both MSCs and exosomes in mitigating the COVID-19 induced cytokine storm as well as promoting the regeneration of alveolar tissue, attributed to the intrinsic cytokines and growth factor present in the secretome. The preliminary studies have demonstrated the safety and efficacy of MSCs and exosomes in mitigating symptoms associated with COVID-19. Thus, they can be used on compassionate basis, owing to their ability to endogenously repair and decrease the inflammatory reactions involved in the morbidity and mortality of COVID-19. However, more preclinical and clinical studies are warranted to understand their mechanism of action and further establish their safety and efficacy.
| S-EPMC7418088 | biostudies-literature
Project description:BackgroundThe novel coronavirus first emerged in Wuhan, China, and quickly spread across the globe, spanning various countries and resulting in a worldwide pandemic by the end of December 2019. Given the current advances in treatments available for COVID-19, mesenchymal stem cell (MSC) therapy seems to be a prospective option for management of ARDS observed in COVID-19 patients. This present study is aimed at exploring the therapeutic potential and safety of using MSC obtained by isolation from health cord tissues in the treatment of patients with COVID-19.MethodsA systematic search was done based on the guidelines of the PRISMA 2020 statement. A literature search was executed using controlled vocabulary and indexing of trials to evaluate all the relevant studies involving the use of medical subject headings (MeSH) in electronic databases like PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov up to 31 December 2021. The protocol was registered in the PROSPERO register with ID CRD42022301666. Findings. After screening finally, 22 remaining articles were included in this systematic review. The studies revealed that MSC exosomes are found to be superior to MSC alone in terms of safety owing to being smaller with a lesser immunological response which leads to free movement in blood capillaries without clumping and also cannot further divide, thus reducing the oncogenic potential of MSC-derived exosomes as compared to MSC only. The studies demonstrated that the lungs healed with the use of exosomes compared to how they presented initially at the hospital. MSCs are found to increase the angiogenesis process and alveolar reepithelization, reducing markers like TNF alpha, TGF beta, and COL I and III, reducing the growth of myofibroblasts and increasing survivability of endothelium leading to attenuated pulmonary fibrosis and even reversing them. Interpretation. We can conclude that the use of mesenchymal stem cells or their derived exosomes is safe and well-tolerated in patients with COVID-19. It improves different parameters of oxygenation and helps in the healing of the lungs. The viral load along with different inflammatory cells and biomarkers of inflammation tend to decrease. Chest X-ray, CT scan, and different radiological tools are used to show improvement and reduced ongoing destructive processes.
| S-EPMC9242780 | biostudies-literature
Project description:BackgroundNo effective pharmacotherapy for acute respiratory distress syndrome (ARDS) exists, and mortality remains high. Preclinical studies support the efficacy of mesenchymal stem (stromal) cells (MSCs) in the treatment of lung injury. We aimed to test the safety of a single dose of allogeneic bone marrow-derived MSCs in patients with moderate-to-severe ARDS.MethodsThe STem cells for ARDS Treatment (START) trial was a multicentre, open-label, dose-escalation, phase 1 clinical trial. Patients were enrolled in the intensive care units at University of California, San Francisco, CA, USA, Stanford University, Stanford, CA, USA, and Massachusetts General Hospital, Boston, MA, USA, between July 8, 2013, and Jan 13, 2014. Patients were included if they had moderate-to-severe ARDS as defined by the acute onset of the need for positive pressure ventilation by an endotracheal or tracheal tube, a PaO2:FiO2 less than 200 mm Hg with at least 8 cm H2O positive end-expiratory airway pressure (PEEP), and bilateral infiltrates consistent with pulmonary oedema on frontal chest radiograph. The first three patients were treated with low dose MSCs (1 million cells/kg predicted bodyweight [PBW]), the next three patients received intermediate dose MSCs (5 million cells/kg PBW), and the final three patients received high dose MSCs (10 million cells/kg PBW). Primary outcomes included the incidence of prespecified infusion-associated events and serious adverse events. The trial is registered with ClinicalTrials.gov, number NCT01775774.FindingsNo prespecified infusion-associated events or treatment-related adverse events were reported in any of the nine patients. Serious adverse events were subsequently noted in three patients during the weeks after the infusion: one patient died on study day 9, one patient died on study day 31, and one patient was discovered to have multiple embolic infarcts of the spleen, kidneys, and brain that were age-indeterminate, but thought to have occurred before the MSC infusion based on MRI results. None of these severe adverse events were thought to be MSC-related.InterpretationA single intravenous infusion of allogeneic, bone marrow-derived human MSCs was well tolerated in nine patients with moderate to severe ARDS. Based on this phase 1 experience, we have proceeded to phase 2 testing of MSCs for moderate to severe ARDS with a primary focus on safety and secondary outcomes including respiratory, systemic, and biological endpoints.FundingThe National Heart, Lung, and Blood Institute.
| S-EPMC4297579 | biostudies-literature
Project description:The COVID-19 pandemic has evoked the scientific community to combine all efforts needed to find a cure for the disease. With the limited therapeutic effects of pharmacological therapies, attention has been drawn to alternative ones such as stem-cell based therapy particularly with mesenchymal stem cells (MSCs). Recently, a large number of clinical trials are ongoing to evaluate the safety and efficacy of MSCs in patients with COVID-19; however, only very few data are released. Thereby, we anxiously await the results of FDA-approved trials to provide more definitive data on the use of MSCs in COVID-19 patients, especially the critically ill. Herein, we shed light on the therapeutic agents that have been tested and used for the treatment of COVID-19 and provide an insight into MSC-based approaches for COVID-19 at both preclinical and clinical levels.
| S-EPMC8661146 | biostudies-literature
Project description:BackgroundAcute respiratory distress syndrome (ARDS) is a fatal complication of coronavirus disease 2019 (COVID-19). There are a few reports of allogeneic human mesenchymal stem cells (MSCs) as a potential treatment for ARDS. In this phase 1 clinical trial, we present the safety, feasibility, and tolerability of the multiple infusions of high dose MSCs, which originated from the placenta and umbilical cord, in critically ill COVID-19-induced ARDS patients.MethodsA total of 11 patients diagnosed with COVID-19-induced ARDS who were admitted to the intensive care units (ICUs) of two hospitals enrolled in this study. The patients were critically ill with severe hypoxemia and required mechanical ventilation. The patients received three intravenous infusions (200 × 106 cells) every other day for a total of 600 × 106 human umbilical cord MSCs (UC-MSCs; 6 cases) or placental MSCs (PL-MSCs; 5 cases).FindingsThere were eight men and three women who were 42 to 66 years of age. Of these, six (55%) patients had comorbidities of diabetes, hypertension, chronic lymphocytic leukemia (CLL), and cardiomyopathy (CMP). There were no serious adverse events reported 24-48 h after the cell infusions. We observed reduced dyspnea and increased SpO2 within 48-96 h after the first infusion in seven patients. Of these seven patients, five were discharged from the ICU within 2-7 days (average: 4 days), one patient who had signs of acute renal and hepatic failure was discharged from the ICU on day 18, and the last patient suddenly developed cardiac arrest on day 7 of the cell infusion. Significant reductions in serum levels of tumor necrosis factor-alpha (TNF-α; P < 0.01), IL-8 (P < 0.05), and C-reactive protein (CRP) (P < 0.01) were seen in all six survivors. IL-6 levels decreased in five (P = 0.06) patients and interferon gamma (IFN-γ) levels decreased in four (P = 0.14) patients. Four patients who had signs of multi-organ failure or sepsis died in 5-19 days (average: 10 days) after the first MSC infusion. A low percentage of lymphocytes (< 10%) and leukocytosis were associated with poor outcome (P = 0.02). All six survivors were well with no complaints of dyspnea on day 60 post-infusion. Radiological parameters of the lung computed tomography (CT) scans showed remarkable signs of recovery.InterpretationWe suggest that multiple infusions of high dose allogeneic prenatal MSCs are safe and can rapidly improve respiratory distress and reduce inflammatory biomarkers in some critically ill COVID-19-induced ARDS cases. Patients that develop sepsis or multi-organ failure may not be good candidates for stem cell therapy. Large randomized multicenter clinical trials are needed to discern the exact therapeutic potentials of MSC in COVID-19-induced ARDS.
| S-EPMC7844804 | biostudies-literature
Project description:The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread into more than 200 countries and infected approximately 203 million people globally. COVID-19 is associated with high mortality and morbidity in some patients, and this disease still does not have effective treatments with reproducibly appreciable outcomes. One of the leading complications associated with COVID-19 is acute respiratory distress syndrome (ARDS); this is an anti-viral host inflammatory response, and it is usually caused by a cytokine storm syndrome which may lead to multi-organ failure and death. Currently, COVID-19 patients are treated with approaches that mostly fall into two major categories: immunomodulators, which promote the body's fight against viruses efficiently, and antivirals, which slow or stop viruses from multiplying. These treatments include a variety of novel therapies that are currently being tested in clinical trials, including serum, IL-6 antibody, and remdesivir; however, the outcomes of these therapies are not consistently appreciable and remain a subject of debate. Mesenchymal stem/stromal cells (MSCs), the multipotent stem cells that have previously been used to treat viral infections and various respiratory diseases such as ARDS exhibit immunomodulatory properties and can ameliorate tissue damage. Given that SARS-CoV-2 targets the immune system and causes tissue damage, it is presumable that MSCs are being explored to treat COVID-19 patients. This review summarizes the potential mechanisms of action of MSC therapy, progress of MSC, and its related products in clinical trials for COVID-19 therapy based on the outcomes of these clinical studies.
| S-EPMC8942612 | biostudies-literature