Systematic review and meta-analysis of mesenchymal stromal/stem cells as strategical means for the treatment of COVID-19
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ABSTRACT: Background:
In coronavirus disease 2019 (COVID-19) patients, elevated levels of
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PROVIDER: S-EPMC10140776 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:Mesenchymal 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. All 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. Use 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:ObjectivesA major challenge for COVID-19 therapy is dysregulated immune response associated with the disease. Umbilical cord mesenchymal stromal cells (UC-MSCs) may be a promising candidate for COVID-19 treatment owing to their immunomodulatory and anti-inflammatory functions. Therefore, this study aimed to evaluate the effectiveness of UC-MSCs inpatients with COVID-19.MethodMedline, Embase, PubMed, Cochrane Library, and Web of Science databases were searched to collect clinical trials concerning UC-MSCs for the treatment of COVID-19. After literature screening, quality assessment, and data extraction, a systematic review and meta-analysis of the included study were performed.ResultsThis systematic review and meta-analysis were prospectively registered on PROSPERO, and the registration number is CRD42022304061. After screening, 10 studies involving 293 patients with COVID-19 were eventually included. Our meta-analysis results showed that UC-MSCs can reduce mortality (relative risk [RR] =0.60, 95% confidence interval [CI]: [0.38, 0.95], P=0.03) in COVID-19 patients. No significant correlation was observed between adverse events and UC-MSC treatment (RR=0.85, 95% CI: [0.65, 1.10], P=0.22; RR=1.00, 95%CI: [0.64, 1.58], P=1.00). In addition, treatment with UC-MSCs was found to suppress inflammation and improve pulmonary symptoms.ConclusionsUC-MSCs hold promise as a safe and effective treatment for COVID-19.Systematic review registartionPROSPERO, identifier CRD42022304061.
| S-EPMC9467457 | biostudies-literature
Project description:BackgroundMesenchymal stromal cells (MSCs) have significant immunomodulatory and tissue repair capabilities, mediated partly by conditioned media or through secreted extracellular vesicles (MSC-EVs). Infection with SARS-CoV-2 can cause mild to life-threatening illness due to activated immune responses that may be dampened by MSCs or their secretome. Many clinical studies of MSCs have been launched since the beginning of the global pandemic, however, few have been completed and most lack power to assess efficacy. Repeated systematic searches and meta-analyses are needed to understand, in real time, the extent of potential benefit in different patient populations as the evidence emerges.MethodsThis living systematic review will be maintained to provide up-to-date information as the pandemic evolves. A systematic literature search of Embase, MEDLINE, and Cochrane Central Register of Controlled Trials databases will be performed. All clinical studies (e.g., randomized, pseudorandomized and non-randomized controlled trials, uncontrolled trials, and case series) employing MSCs or their secretome as a therapeutic intervention for COVID-19 will be included. Patients must have confirmed SARS-CoV-2 infection. Study screening and data extraction will be performed in duplicate. Information concerning interventions, patient populations, methods of MSC isolation and characterization, primary and secondary clinical and/or laboratory outcomes, and adverse events will be extracted. Key clinical outcomes will be pooled through random-effects meta-analysis to determine the efficacy of MSCs and their secreted products for COVID-19.DiscussionOur systematic review and subsequent updates will inform the scientific, medical, and health policy communities as the pandemic evolves to guide decisions on the appropriate use of MSC-related products to treat COVID-19.Systematic review registrationPROSPERO CRD 42021225431.
| S-EPMC8441251 | biostudies-literature
Project description:IntroductionTo date, no specific antivirus drugs or vaccines have been available to prevent or treat the COVID-19 pandemic. Mesenchymal stem cell (MSC) therapy may be a promising therapeutic approach that reduces the high mortality in critical cases. This protocol is proposed for a systematic review and meta-analysis that aims to evaluate the efficacy and safety of MSC therapy on patients with COVID-19.Methods and analysisTen databases including PubMed, EMBASE, Cochrane Library, CINAHL, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wanfang database, China Biomedical Literature Database (CBM) and Chinese Biomedical Literature Service System (SinoMed) will be searched from inception to 1 December 2020. All published randomised controlled trials, clinical controlled trials and case series that meet the prespecified eligibility criteria will be included. The primary outcomes include mortality, incidence and severity of adverse events, respiratory improvement, days from ventilator, duration of fever, progression rate from mild or moderate to severe, improvement of such serious symptoms as difficulty breathing or shortness of breath, chest pain or pressure, and loss of speech or movement, biomarkers of laboratory examination and changes in CT. The secondary outcomes include dexamethasone doses and quality of life. Two reviewers will independently perform study selection, data extraction and assessment of bias risk. Data synthesis will be conducted using RevMan software (V.5.3.5). If necessary, subgroup and sensitivity analysis will be performed. Grading of Recommendations Assessment, Development and Evaluation system will be used to assess the strength of evidence.Ethics and disseminationEthical approval is not necessary since no individual patient or privacy data have been collected. The results of this review will be disseminated in a peer-reviewed journal or an academic conference presentation.Prospero registration numberCRD42020190079.
| S-EPMC7750871 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a global pandemic since late 2019 that resulted in more than 360 million population infection. Among them, less than 7% of infected individuals develop severe or critical illness. Mass vaccination has been carried out, but reinfection and vaccine breakthrough cases still occur. Besides supportive and antiviral medications, much attention has been paid in immunotherapies that aim at reducing pathological changes in the lungs. Mesenchymal stem cells (MSCs) is used as an option because of their immunomodulatory, anti-inflammatory, and regenerative properties. As of January 16, 2022, when ClinicalTrials.gov was searched for "Mesenchymal stem cells and COVID-19," over 80 clinical trials were registered. MSC therapy was found to be safe and some effective in preclinical and clinical studies. Here, we summarize the major pathological characteristics of COVID-19 and provide scientific and rational evidence for the safety and possible effectiveness of MSCs in COVID-19 treatment.
| S-EPMC8907937 | biostudies-literature
Project description:New coronavirus disease 2019 (COVID-19), as a pandemic disaster, has drawn the attention of researchers in various fields to discover suitable therapeutic approaches for the management of COVID-19 patients. Currently, there are many worries about the rapid spread of COVID-19; there is no approved treatment for this infectious disease, despite many efforts to develop therapeutic procedures for COVID-19. Emerging evidence shows that mesenchymal stromal/stem cell (MSC) therapy can be a suitable option for the management of COVID-19. These cells have many biological features (including the potential of differentiation, high safety and effectiveness, secretion of trophic factors and immunoregulatory features) that make them suitable for the treatment of various diseases. However, some studies have questioned the positive role of MSC therapy in the treatment of COVID-19. Accordingly, in this paper, we will focus on the therapeutic impacts of MSCs and their critical role in cytokine storm of COVID-19 patients.
| S-EPMC8652792 | biostudies-literature
Project description:Stem cells are considered to be one of the greatest potential treatments to cure degenerative diseases. Stem cells injection for knee osteoarthritis (OA) is still a relatively new treatment and has not yet gained popularity. So, the effectiveness, safety and potential of mesenchymal stem cells (MSCs) for knee OA treatment is worthy to be explored. Explore the effectiveness and safety of mesenchymal stem cells (MSCs) in the treatment of knee osteoarthritis. We collected clinical trials using MSCs as treatment for knee OA (before April 2019), including randomized controlled trials (RCTs), retrospective studies and cohort studies. We searched PubMed, EMBASE, Cochrane Library, Web of Science and the ClinicalTrials.gov with keywords (Mesenchymal stem cells [MSCs], Knee osteoarthritis, Effectiveness and Safety), and then performed a systematic review and cumulative metaanalysis of all RCTs and retrospective comparative studies. To evaluate the effectiveness and safety of MSC in knee OA treatment, we applied visual analog scale score, Western Ontario and McMaster Universities Osteo-arthritis Index and adverse events. We included 15 RCTs, two retrospective studies and two cohort studies including a total of 584 knee OA patients in this study. We demonstrated that MSC treatment could significantly decrease visual analog scale in a 12-month follow-up study compared with controls (p < 0.001). MSC therapy also showed significant decreases in Western Ontario and McMaster Universities Osteoarthritis Index scores after the 6-month follow-up (p < 0.001). MSC therapy showed no difference compared with controls (p > 0.05) in adverse events. We suggest that MSC therapy could serve as an effective and safe therapy for clinical application in OA treatment.The translational potential of this articleThis study provided the best available evidence and a wider perspective to MSCs application in the management of knee OA. MSCs therapy will have great translational potential in the clinical treatment of various degenerative diseases once optimum formula and explicit target population are identified.
| S-EPMC7452318 | biostudies-literature
Project description:BackgroundThe present study aims to better understand the efficacy and safety of mesenchymal stromal cells (MSCs) in treating severe/critical patients with COVID-19.MethodsPubMed, the Cochrane Library, and the Chinese electronic database CNKI were searched from inception up to Dec 19, 2021. Original comparative studies for MSC treatment + standard treatment for severe/critical patients with COVID-19, with placebo or standard treatment as the control group, were included. The primary outcomes were in-hospital mortality and adverse events (AEs). A meta-analysis was performed to compare the mortality rates between the two groups. Then, a subgroup analysis was performed according to the category of the disease (severe or critical) and MSC dose. Afterwards, a descriptive analysis was performed for AEs and secondary outcomes. The funnel plot and Egger's test were used for the publication bias assessment.FindingsCompared to placebo or standard care, MSCs provide significant benefit in the treatment of patients with severe/critical COVID-19, in terms of in-hospital mortality rate (odds ratio: 0.52, 95% CI 0.32-0.84), with very low heterogeneity (P=0.998 [Q test], I 2=0.0%) and less AEs. No significant difference was found in mortality rate due to the different disease categories or MSC doses. Furthermore, no publication bias was found.InterpretationThe present study demonstrates that MSCs are highly likely to reduce mortality and are safe to use for patients with severe or critical COVID-19, regardless of whether 1-3 doses are applied. However, due to the small sample size of the included studies, further high-quality, large-scale trials are needed to confirm this statement in the future.FundingThe National Key Research and Development Program of China (No. 2020YFC0860900), the Science and Technology Project of Wuhan (No. 2020020602012112), the Tianjin Science and Technology Research Program (18PTSYJC00070 and 16PTWYHZ00030), Haihe Laboratory of Cell Ecosystem Innovation Fund (HH22KYZX0046), and the Tianjin Free Trade Zone Innovation Development Project (ZMCY-03-2021002-01) funded the study. We are also grateful for the support from the 3551 Talent Plan of China Optics Valley.
| S-EPMC9270852 | 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:Since the emergence of the coronavirus disease 2019 (COVID-19) pandemic, many lives have been tragically lost to severe infections. The COVID-19 impact extends beyond the respiratory system, affecting various organs and functions. In severe cases, it can progress to acute respiratory distress syndrome (ARDS) and multi-organ failure, often fueled by an excessive immune response known as a cytokine storm. Mesenchymal stem cells (MSCs) have considerable potential because they can mitigate inflammation, modulate immune responses, and promote tissue regeneration. Accumulating evidence underscores the efficacy and safety of MSCs in treating severe COVID-19 and ARDS. Nonetheless, critical aspects, such as optimal routes of MSC administration, appropriate dosage, treatment intervals, management of extrapulmonary complications, and potential pediatric applications, warrant further exploration. These research avenues hold promise for enriching our understanding and refining the application of MSCs in confronting the multifaceted challenges posed by COVID-19.
| S-EPMC10573267 | biostudies-literature