Delayed MSC therapy enhances resolution of organized pneumonia induced by antibiotic resistant infection.

Introduction: Mesenchymal stromal cells (MSC) are a promising therapeutic for pneumonia-induced sepsis. Here we sought to determine the efficacy of delayed administration of naïve and activated bone marrow (BM), adipose (AD), and umbilical cord (UC) derived MSCs in organized antibiotic resistant pneumosepsis.

Methods: Human BM-, AD-, and UC-MSCs were isolated and expanded and used either in the naïve state or following cytokine pre-activation.

Nebulised mesenchymal stem cell derived extracellular vesicles ameliorate E. coli induced pneumonia in a rodent model.

Background: Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) have been proposed as an alternative to cell therapy, creating new possible delivery modalities such as nebulisation. We wished to investigate the therapeutic potential of directly nebulised MSC-EVs in the mitigation of Escherichia coli-induced pneumonia.

Methods: EV size, surface markers and miRNA content were assessed pre- and post-nebulisation.

Differential Effects of Cytokine Versus Hypoxic Preconditioning of Human Mesenchymal Stromal Cells in Pulmonary Sepsis Induced by Antimicrobial-Resistant .

: Pulmonary sepsis is a leading cause of hospital mortality, and sepses arising from antimicrobial-resistant (AMR) bacterial strains are particularly difficult to treat. Here we investigated the potential of mesenchymal stromal cells (MSCs) to combat established pneumosepsis and further evaluated MSC preconditioning and pre-activation methods. : The potential for naïve and preconditioned MSCs to enhance wound healing, reduce inflammation, preserve metabolic activity, and enhance bacterial killing was assessed in vitro.

Multiple Dosing and Preactivation of Mesenchymal Stromal Cells Enhance Efficacy in Established Pneumonia Induced by Antimicrobial-Resistant in Rodents.

Antimicrobial-resistant (AMR) bacteria, such as species, are an increasingly common cause of hospital-acquired pneumonia, resulting in high mortality and morbidity. Harnessing the host immune response to AMR bacterial infection using mesenchymal stem cells (MSCs) is a promising approach to bypass bacterial AMR mechanisms. The administration of single doses of naïve MSCs to ARDS clinical trial patient cohorts has been shown to be safe, although efficacy is unclear.

Aerosolized Pulmonary Delivery of mRNA Constructs Attenuates Severity of Pneumonia in the Rat.

Acute respiratory distress syndrome (ARDS), a rapid onset inflammatory lung disease with no effective specific therapy, typically has pathogenic etiology termed pneumonia. In previous studies nuclear factor-κB (NF-κB) inhibitor α super-repressor (IκBα-SR) and extracellular superoxide dismutase 3 (SOD3) reduced pneumonia severity when prophylactically delivered by viral vector. In this study, mRNA coding for green fluorescent protein, IκBα-SR, or SOD3 was complexed with cationic lipid, passed through a vibrating mesh nebulizer, and delivered to cell culture or directly to rats undergoing pneumonia.

Enhancement strategies for mesenchymal stem cells and related therapies.

Cell therapy, particularly mesenchymal stem/stromal (MSC) therapy, has been investigated for a wide variety of disease indications, particularly those with inflammatory pathologies. However, recently it has become evident that the MSC is far from a panacea. In this review we will look at current and future strategies that might overcome limitations in efficacy.

Hypercapnia in the critically ill: insights from the bench to the bedside.

Carbon dioxide (CO) has long been considered, at best, a waste by-product of metabolism, and at worst, a toxic molecule with serious health consequences if physiological concentration is dysregulated. However, clinical observations have revealed that 'permissive' hypercapnia, the deliberate allowance of respiratory produced CO to remain in the patient, can have anti-inflammatory effects that may be beneficial in certain circumstances. In parallel, studies at the cell level have demonstrated the profound effect of CO on multiple diverse signalling pathways, be it the effect from CO itself specifically or from the associated acidosis it generates.

Mesenchymal Stem/Stromal Cells Therapy for Sepsis and Acute Respiratory Distress Syndrome.

Sepsis and acute respiratory distress syndrome (ARDS) constitute devastating conditions with high morbidity and mortality. Sepsis results from abnormal host immune response, with evidence for both pro- and anti-inflammatory activation present from the earliest phases. The "proinflammatory" response predominates initially causing host injury, with later-phase sepsis characterized by immune cell hypofunction and opportunistic superinfection.