Mesenchymal stem cell therapy for acute respiratory distress syndrome: a light at the end of the tunnel?
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ABSTRACT:
SUBMITTER: Lee JW
PROVIDER: S-EPMC4301977 | biostudies-literature | 2015 Feb
REPOSITORIES: biostudies-literature
Publications
Mesenchymal stem cell therapy for acute respiratory distress syndrome: a light at the end of the tunnel?
Lee Jae-Woo JW Rocco Patricia R M PR Pelosi Paolo P
Anesthesiology 20150201 2
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Project description:Acute respiratory distress syndrome (ARDS) is a devastating hypoxemic respiratory failure, characterized by disruption of the alveolar-capillary membrane barrier. Current management for ARDS remains supportive, including lung-protective ventilation and a conservative fluid strategy. Mesenchymal stem cells (MSCs) have emerged as a potentially attractive candidate for the management of ARDS through facilitating lung tissue regeneration and repair by releasing paracrine soluble factors. Over the last decade, a variety of strategies have emerged to optimize MSC-based therapy. Among these, the strategy using genetically modified MSCs has received increased attention recently due to its distinct advantage, in conferring incremental migratory capacity and, enhancing the anti-inflammatory, immunomodulatory, angiogenic, and antifibrotic effects of these cells in numerous preclinical ARDS models, which may in turn provide additional benefits in the management of ARDS. Here, we provide an overview of recent studies testing the efficacy of genetically modified MSCs using preclinical models of ARDS.
| S-EPMC6915956 | biostudies-literature
Project description:The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.
| S-EPMC7282699 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), is growing at an exponential rate worldwide. Manifestations of this disease are heterogeneous; however, advanced cases often exhibit various acute respiratory distress syndrome-like symptoms, systemic inflammatory reactions, coagulopathy, and organ involvements. A common theme in advanced COVID-19 is unrestrained immune activation, classically referred to as a "cytokine storm", as well as deficiencies in immune regulatory mechanisms such as T regulatory cells. While mesenchymal stem cells (MSCs) themselves are objects of cytokine regulation, they can secrete cytokines to modulate immune cells by inducing anti-inflammatory regulatory Treg cells, macrophages and neutrophils; and by reducing the activation of T and B cells, dendritic and nature killer cells. Consequently, they have therapeutic potential for treating severe cases of COVID-19. Here we discuss the unique ability of MSCs, to act as a "living anti-inflammatory", which can "rebalance" the cytokine/immune responses to restore equilibrium. We also discuss current MSC trials and present different concepts for optimization of MSC therapy in patients with COVID-19 acute respiratory distress syndrome.
| S-EPMC7596438 | biostudies-literature
Project description:Five COVID-19-related ARDS patients who consented to compassionate placenta-derived (pc)-MSC treatment were followed for clinical response and disease progression. Serum samples were collected before and after pc-MSC infusion for quantitative proteomics analysis.
2023-07-13 | PXD043740 | JPOST Repository
Project description: Not available
| S-EPMC3576439 | biostudies-literature
Project description:Acute respiratory distress syndrome (ARDS) is driven by a severe pro-inflammatory response resulting in lung damage, impaired gas exchange and severe respiratory failure. There is no specific treatment that effectively improves outcome in ARDS. However, in recent years, cell therapy has shown great promise in preclinical ARDS studies. A wide range of cells have been identified as potential candidates for use, among these are mesenchymal stromal cells (MSCs), which are adult multi-lineage cells that can modulate the immune response and enhance repair of damaged tissue. The therapeutic potential of MSC therapy for sepsis and ARDS has been demonstrated in multiple in vivo models. The therapeutic effect of these cells seems to be due to two different mechanisms; direct cellular interaction, and paracrine release of different soluble products such as extracellular vesicles (EVs)/exosomes. Different approaches have also been studied to enhance the therapeutic effect of these cells, such as the over-expression of anti-inflammatory or pro-reparative molecules. Several clinical trials (phase I and II) have already shown safety of MSCs in ARDS and other diseases. However, several translational issues still need to be addressed, such as the large-scale production of cells, and their potentiality and variability, before the therapeutic potential of stem cells therapies can be realized.
| S-EPMC6196176 | biostudies-literature
Project description:Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome that leads to acute respiratory failure and accounts for over 70,000 deaths per year in the United States alone, even prior to the COVID-19 pandemic. While its molecular details have been teased apart and its pathophysiology largely established over the past 30 years, relatively few pharmacological advances in treatment have been made based on this knowledge. Indeed, mortality remains very close to what it was 30 years ago. As an alternative to traditional pharmacological approaches, gene therapy offers a highly controlled and targeted strategy to treat the disease at the molecular level. Although there is no single gene or combination of genes responsible for ARDS, there are a number of genes that can be targeted for upregulation or downregulation that could alleviate many of the symptoms and address the underlying mechanisms of this syndrome. This review will focus on the pathophysiology of ARDS and how gene therapy has been used for prevention and treatment. Strategies for gene delivery to the lung, such as barriers encountered during gene transfer, specific classes of genes that have been targeted, and the outcomes of these approaches on ARDS pathogenesis and resolution will be discussed.
| S-EPMC8801611 | biostudies-literature
Project description:Acute respiratory distress syndrome (ARDS) is a serious and potentially fatal acute inflammatory lung condition which currently has no specific treatments targeting its pathophysiology. However, mesenchymal stem cells have been shown to have very promising therapeutic potential, and recently, it has been established that their effect is largely due to the transfer of extracellular vesicles (EVs). EVs have been shown to transfer a variety of substances such as mRNA, miRNA, and even organelles such as mitochondria in order to ameliorate ARDS in preclinical models. In addition, the fact that they have been proven to have the same effect as their parent cells combined with their numerous advantages over whole cell administration means that they are a promising candidate for clinical application that merits further research.
| S-EPMC6954712 | biostudies-literature
Project description:BackgroundMesenchymal stem cells (MSC) therapy for acute respiratory distress syndrome (ARDS) represents a burgeoning treatment approach, supported by numerous preclinical studies confirming its efficacy. Our study aims to provide a comprehensive evaluation of both the safety and effectiveness of MSC.MethodsWe conducted searches across three databases (PubMed, Embase, Cochrane) for randomized controlled studies up to June 23, 2024. A meta-analysis was performed on variables including adverse events, mortality, changes in the PaO2/FiO2 ratio, intensive care unit (ICU), length of stay, ventilation-free days, and changes in pro-inflammatory and anti-inflammatory cytokines. Relative risk (RR) values were employed for dichotomous variables, while mean difference (MD) and standard mean difference (SMD) were used for continuous variables. Risk bias was assessed using risk of bias 2 (ROB2).ResultsThe meta-analysis encompassed 17 experiments involving 796 patients, with 410 undergoing MSC treatment and 386 in the control group. Primary outcomes indicated that MSC treatment did not escalate adverse events [RR =1.04; 95% confidence interval (CI): 0.90, 1.19; P=0.59; I2=0%]. On the contrary, it significantly diminishes the mortality (RR =0.79; 95% CI: 0.64, 0.97; P=0.02; I2=0%). Regarding secondary outcomes, MSCs led to a significant improvement in the PaO2/FiO2 ratio for ARDS patients (SMD =0.53; 95% CI: 0.15, 0.92; P=0.007; I2=0%). However, there were no significant differences in ICU length of stay (MD =-1.77; 95% CI: -6.97, 3.43; P=0.50; I2=63%) and ventilation-free days (MD =-1.29; 95% CI: -4.09, 1.51; P=0.37; I2=0%). MSCs significantly lowered C-reactive protein (CRP) (SMD =-0.65; 95% CI: -1.18, -0.13; P=0.01; I2=56%) and interleukin-6 (IL-6) levels compared to the control group (SMD =-0.76; 95% CI: -1.34, -0.17; P=0.01; I2=74%). However, changes in interleukin-10 (AIL-10) (SMD =-0.46; 95% CI: -1.51, 0.58; P=0.38; I2=77%), and changes in tumor necrosis factor-alpha (ATNF-α) (SMD =-1.5; 95% CI: -3.39, 0.40; P=0.12; I2=92%) levels showed no significant changes.ConclusionsMSC therapy demonstrates reliable safety, with a significant impact on reducing mortality and improving certain clinical symptoms. Moreover, in certain aspects, it may alleviate the inflammatory response in ARDS. Nonetheless, these findings necessitate validation through additional high-quality randomized controlled trials.
| S-EPMC11494583 | biostudies-literature
Project description:Background aimsThe acute respiratory distress syndrome (ARDS) resulting from coronavirus disease 2019 (COVID-19) is associated with a massive release of inflammatory cytokines and high mortality. Mesenchymal stromal cells (MSCs) have anti-inflammatory properties and have shown activity in treating acute lung injury. Here the authors report a case series of 11 patients with COVID-19-associated ARDS (CARDS) requiring mechanical ventilation who were treated with remestemcel-L, an allogeneic MSC product, under individual patient emergency investigational new drug applications.MethodsPatients were eligible if they were mechanically ventilated for less than 72 h prior to the first infusion. Patients with pre-existing lung disease requiring supplemental oxygen or severe liver or kidney injury were excluded. Each patient received two infusions of remestemcel-L at a dose of 2 million cells/kg per infusion given 48-120 h apart.ResultsRemestemcel-L infusions were well tolerated in all 11 patients. At the end of the 28-day follow-up period, 10 (91%, 95% confidence interval [CI], 59-100%) patients were extubated, nine (82%, 95% CI, 48-97%) patients remained liberated from mechanical ventilation and were discharged from the intensive care unit and two (18%, 95 CI%, 2-52%) patients died. The median time to extubation was 10 days. Eight (73%, 95% CI, 34-100%) patients were discharged from the hospital. C-reactive protein levels significantly declined within 5 days of MSC infusion.ConclusionsThe authors demonstrate in this case series that remestemcel-L infusions to treat moderate to severe CARDS were safe and well tolerated and resulted in improved clinical outcomes.
| S-EPMC8995321 | biostudies-literature