Administration of mesenchymal stem cells during ECMO results in a rapid decline in oxygenator performance

Millar, Jonathan; Bahr, Viktor von; Malfertheiner, Maximilian; Ki, Katrina K; Redd, Meredith A.; Bartnikowski, Nicole; Suen, Jacky Y.; McAuley, Daniel F.; Fraser, John F.

doi:10.1136/thoraxjnl-2017-211439

Cited by 27 publications

(27 citation statements)

References 10 publications

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“…1). The anti-inflammatory effects of MSCs have been mostly attributed to their release of paracrine factors, because of low engraftment of donorderived MSCs into at the host lung tissue after MSC therapy (Qin et al, 2012;Millar et al, 2019). In support of this, MSCconditioned media have been suggested to reduce pro-inflammatory mediator levels and inflammatory cell counts in ARDS models (Ionescu et al, 2012;Goolaerts et al, 2014;Chen et al, 2015;Su et al, 2019;Xu et al, 2019).…”

Section: Induction Of Anti-inflammatory Responsementioning

confidence: 99%

Mesenchymal stem cell therapy for acute respiratory distress syndrome: from basic to clinics

2020

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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.

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Section: Induction Of Anti-inflammatory Responsementioning

confidence: 99%

Mesenchymal stem cell therapy for acute respiratory distress syndrome: from basic to clinics

2020

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“…Importantly, ECMO has become an increasingly common therapeutic modality for patients with severe ARDS (Bellani et al 2016;Papazian et al 2019). In an ex vivo model, MSCs administered intravascularly were found to adhere to membrane oxygenator fibers during ECMO, resulting in a significant reduction of flow through the circuit (Millar et al 2019). Further investigations should be performed with alternative routes of administration, such as intrabronchial, to identify which would be a viable option for this clinical situation.…”

Section: Clinical Trials Of Msc Therapy In Patients With Ardsmentioning

confidence: 99%

Current understanding of the therapeutic benefits of mesenchymal stem cells in acute respiratory distress syndrome

et al. 2019

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The acute respiratory distress syndrome (ARDS) is a multifaceted lung disorder in which no specific therapeutic intervention is able to effectively improve clinical outcomes. Despite an improved understanding of molecular mechanisms and advances in supportive care strategies, ARDS remains associated with high mortality, and survivors usually face longterm morbidity. In recent years, preclinical studies have provided mounting evidence of the potential of mesenchymal stem cell (MSC)-based therapies in lung diseases and critical illnesses. In several models of ARDS, MSCs have been demonstrated to induce antiinflammatory and anti-apoptotic effects, improve epithelial and endothelial cell recovery, and enhance microbial and alveolar fluid clearance, thus resulting in improved lung and distal organ function and survival. Early-stage clinical trials have also demonstrated the safety of MSC administration in patients with ARDS, but further, large-scale investigations are required to assess the safety and efficacy profile of these therapies. In this review, we summarize the main mechanisms whereby MSCs have been shown to exert therapeutic effects in experimental ARDS. We also highlight questions that need to be further elucidated and barriers that must be overcome in order to efficiently translate MSC research into clinical practice.

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“…However, the application of MSC in patients treated with ECMO needs further thorough clinical investigation. Recently, Millar et al demonstrated a rapid decline in oxygenator performance in an ex-vivo model of ECMO [41]. Another group evaluated the viability and activity of MSC in ex vivo circulation conditions with and without an oxygenator [42].…”

Section: Discussionmentioning

confidence: 99%

Increased mobilization of mesenchymal stem cells in patients with acute respiratory distress syndrome undergoing extracorporeal membrane oxygenation

et al. 2020

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BackgroundThe acute respiratory distress syndrome (ARDS) is characterized by pulmonary epithelial and endothelial barrier dysfunction and injury. In severe forms of ARDS, extracorporeal membrane oxygenation (ECMO) is often the last option for life support. Endothelial progenitor (EPC) and mesenchymal stem cells (MSC) can regenerate damaged endothelium and thereby improve pulmonary endothelial dysfunction. However, we still lack sufficient knowledge about how ECMO might affect EPC-and MSC-mediated regenerative pathways in ARDS. Therefore, we investigated if ECMO impacts EPC and MSC numbers in ARDS patients. MethodsPeripheral blood mononuclear cells from ARDS patients undergoing ECMO (n = 16) and without ECMO support (n = 12) and from healthy volunteers (n = 16) were isolated. The number and presence of circulating EPC and MSC was detected by flow cytometry. Serum concentrations of vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2) were determined.

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Administration of mesenchymal stem cells during ECMO results in a rapid decline in oxygenator performance

Cited by 27 publications

References 10 publications

Mesenchymal stem cell therapy for acute respiratory distress syndrome: from basic to clinics

Mesenchymal stem cell therapy for acute respiratory distress syndrome: from basic to clinics

Current understanding of the therapeutic benefits of mesenchymal stem cells in acute respiratory distress syndrome

Increased mobilization of mesenchymal stem cells in patients with acute respiratory distress syndrome undergoing extracorporeal membrane oxygenation

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