The critical role of mesenchymal stromal/stem cell therapy in COVID-19 patients: An updated review.
Ontology highlight
ABSTRACT:
SUBMITTER: Ebrahimi M
PROVIDER: S-EPMC8652792 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:One of the main causes of acute respiratory distress syndrome in coronavirus disease 2019 (COVID-19) is cytokine storm, although the exact cause is still unknown. Umbilical cord mesenchymal stromal cells (UC-MSCs) influence proinflammatory T-helper 2 (Th2 ) cells to shift to an anti-inflammatory agent. To investigate efficacy of UC-MSC administration as adjuvant therapy in critically ill patients with COVID-19, we conducted a double-blind, multicentered, randomized controlled trial at four COVID-19 referral hospitals in Jakarta, Indonesia. This study included 40 randomly allocated critically ill patients with COVID-19; 20 patients received an intravenous infusion of 1 × 106 /kg body weight UC-MSCs in 100 ml saline (0.9%) solution (SS) and 20 patients received 100 ml 0.9% SS as the control group. All patients received standard therapy. The primary outcome was measured by survival rate and/or length of ventilator usage. The secondary outcome was measured by clinical and laboratory improvement, with serious adverse events. Our study showed the survival rate in the UC-MSCs group was 2.5 times higher than that in the control group (P = .047), which is 10 patients and 4 patients in the UC-MSCs and control groups, respectively. In patients with comorbidities, UC-MSC administration increased the survival rate by 4.5 times compared with controls. The length of stay in the intensive care unit and ventilator usage were not statistically significant, and no adverse events were reported. The application of infusion UC-MSCs significantly decreased interleukin 6 in the recovered patients (P = .023). Therefore, application of intravenous UC-MSCs as adjuvant treatment for critically ill patients with COVID-19 increases the survival rate by modulating the immune system toward an anti-inflammatory state.
| S-EPMC8242692 | biostudies-literature
Project description:The coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) started in December 2019 and affected the whole world in a short time. The course of the disease depends on the person's immune system, physical properties, health status, etc. as it varies according to its characteristics while it is asymptomatic in some people, it causes fatal processes that start with flu-like symptoms such as cough, fever, respiratory distress in some people and progress to acute respiratory distress syndrome (ARDS), severe pneumonia and multi-organ dysfunction, and the basic mechanism underlying these effects known as a cytokine storm. There is no specific effective antiviral drug or vaccine in treatment yet. Supportive/alternative treatment methods are needed as both the desired effect cannot be achieved and undesirable side effects are seen with the current treatments used in the clinic. Mesenchymal stem cells (MSCs) are frequently preferred recently from basic studies to clinical studies and are effective and safe in immune-mediated inflammatory diseases such as Systemic Lupus Erythematosus, Graft-versus-Host disease. MSCs can secrete many types of cytokines through paracrine secretion or directly interact with immune cells leading to immunomodulation. According to the results of the completed studies; it has been stated that the cytokine storm caused by the overstimulation of the immune system decreases and even damage of the cytokine storm on organs decreases, respiratory distress is relieved and contributes to the healing process by repairing damaged tissues. In this review, clinical trials completed/ongoing on MSCs recommended for treating COVID-19, a global problem, are reviewed and the review is prepared to specify the existence of such a route to clinicians.
| S-EPMC8784829 | biostudies-literature
Project description:Stem cell transplantation is a potential therapeutic option to regenerate damaged myocardium and restore function after infarct. Current research is focused on the use of allogeneic mesenchymal stem cells (MSCs) due to their unique immunomodulatory characteristics and ability to be harvested from young and healthy donors. Both animal and human studies support the immunoprivileged state of MSCs and even demonstrate improvements in cardiac function after transplantation. This research continues to be a topic of interest, as advances will ultimately enable the clinical use of these universal cells for therapy after a myocardial infarction. Updated in vitro, in vivo, and clinical trial studies are discussed in detail in the following review.
| S-EPMC4709780 | biostudies-other
Project description:The COVID-19 disease is caused by a positive stranded RNA virus called SARS-CoV-2. The virus mainly targets the pulmonary epithelial cells as it's initial site of infection by letting its surface spike protein interact and bind to the host ACE2 receptor. The internalization and gradual replication of the virus results in an exaggerated immune response triggering release of many pro-inflammatory cytokines and chemokines. This immune storm is responsible for multiple health hazards in the host ultimately leading to multiple organ failure. Mesenchymal stem cell therapy offers a promising approach towards mitigating the delirious effects of the infection in the COVID-19 patients. This therapy has shown to reduce the expression of pro-inflammatory cytokines as well as repair of damaged tissues in COVID-19 patients. This review has been organized to put forward the positive aruments and implications in support of mesenchymal stem cell therapy as a necessary approach for treating COVID-19 patients.
| S-EPMC7224671 | biostudies-literature
Project description:The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has placed a global public burden on health authorities. Although the virological characteristics and pathogenesis of COVID-19 has been largely clarified, there is currently no specific therapeutic measure. In severe cases, acute SARS-CoV-2 infection leads to immune disorders and damage to both the adaptive and innate immune responses. Having roles in immune regulation and regeneration, mesenchymal stem cells (MSCs) serving as a therapeutic option may regulate the over-activated inflammatory response and promote recovery of lung damage. Since the outbreak of the COVID-19 pandemic, a series of MSC-therapy clinical trials has been conducted. The findings indicate that MSC treatment not only significantly reduces lung damage, but also improves patient recovery with safety and good immune tolerance. Herein, we summarize the recent progress in MSC therapy for COVID-19 and highlight the challenges in the field.
| S-EPMC8424619 | 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
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:The novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Mesenchymal stem cells (MSCs) are currently utilized in clinics for pulmonary inflammatory diseases, including acute respiratory distress syndrome and acute lung injury. Given that MSCs offer a promising treatment against COVID-19, they are being used against COVID-19 in more than 70 clinical trials with promising findings. Genetically engineered MSCs offer promising therapeutic options in pulmonary diseases. However, their potential has not been explored yet. In this review, we provide perspectives on the functionally modified MSCs that can be developed and harnessed for COVID-19 therapy. Options to manage the SARS-CoV-2 infection and its variants using various bioengineering tools to increase the therapeutic efficacy of MSCs are highlighted.
| S-EPMC8834073 | biostudies-literature
Project description:BackgroundMesenchymal stem/stromal cells (MSCs) and their secreted products are a promising therapy for COVID-19 given their immunomodulatory and tissue repair capabilities. Many small studies were launched at the onset of the pandemic, and repeated meta-analysis is critical to obtain timely and sufficient statistical power to determine efficacy.Methods and findingsAll English-language published studies identified in our systematic search (up to February 3, 2021) examining the use of MSC-derived products to treat patients with COVID-19 were identified. Risk of bias (RoB) was assessed for all studies. Nine studies were identified (189 patients), four of which were controlled (93 patients). Three of the controlled studies reported on mortality (primary analysis) and were pooled through random-effects meta-analysis. MSCs decreased the risk of death at study endpoint compared with controls (risk ratio, 0.18; 95% confidence interval [CI], 0.04 to 0.74; P = .02; I2 = 0%), although follow-up differed. Among secondary outcomes, interleukin-6 levels were most commonly reported and were decreased compared with controls (standardized mean difference, -0.69; 95% CI, -1.15 to -0.22; P = .004; I2 = 0%) (n = 3 studies). Other outcomes were not reported consistently, and pooled estimates of effect were not performed. Substantial heterogeneity was observed between studies in terms of study design. Adherence to published ISCT criteria for MSC characterization was low. In two of nine studies, RoB analysis revealed a low to moderate risk of bias in controlled studies, and uncontrolled case series were of good (3 studies) or fair (2 studies) quality.ConclusionUse of MSCs to treat COVID-19 appears promising; however, few studies were identified, and potential risk of bias was detected in all studies. More controlled studies that report uniform clinical outcomes and use MSC products that meet standard ISCT criteria should be performed. Future iterations of our systematic search should refine estimates of efficacy and clarify potential adverse effects.
| S-EPMC8802614 | biostudies-literature
Project description:The aim of this clinical trial was to control the cytokine storm by administering mesenchymal stem cells (MSCs) to critically-ill COVID-19 patients, to evaluate the healing effect, and to systematically investigate how the treatment works. Patients with moderate and critical COVID-19 clinical manifestations were separated as Group 1 (moderate cases, n = 10, treated conventionally), Group 2 (critical cases, n = 10, treated conventionally), and Group 3 (critical cases, n = 10, treated conventionally plus MSCs transplantation therapy of three consecutive doses on treatment days 0, 3, and 6, (as 3 × 106 cells/kg, intravenously). The treatment mechanism of action was investigated with evaluation markers of the cytokine storm, via biochemical parameters, levels of proinflammatory and anti-inflammatory cytokines, analyses of tissue regeneration via the levels of growth factors, apoptosis markers, chemokines, matrix metalloproteinases, and granzyme-B, and by the assessment of the immunomodulatory effects via total oxidant/antioxidant status markers and the levels of lymphocyte subsets. In the assessment of the overall mortality rates of all the cases, six patients in Group-2 and three patients in Group-3 died, and there was no loss in Group-1. Proinflammatory cytokines IFNγ, IL-6, IL-17A, IL-2, IL-12, anti-inflammatory cytokines IL-10, IL-13, IL-1ra, and growth factors TGF-β, VEGF, KGF, and NGF levels were found to be significant in Group-3. When Group-2 and Group-3 were compared, serum ferritin, fibrinogen and CRP levels in Group-3 had significantly decreased. CD45 +, CD3 +, CD4 +, CD8 +, CD19 +, HLA-DR +, and CD16 + / CD56 + levels were evaluated. In the statistical comparison of the groups, significance was only determined in respect of neutrophils. The results demonstrated the positive systematic and cellular effects of MSCs application on critically ill COVID-19 patients in a versatile way. This effect plays an important role in curing and reducing mortality in critically ill patients.
| S-EPMC8243094 | biostudies-literature