Concise Review: Mesenchymal Stromal Cell-Based Approaches for the Treatment of Acute Respiratory Distress and Sepsis Syndromes

Abstract

Despite extensive research on candidate pharmacological treatments and a significant and increasing prevalence, sepsis syndrome, and acute respiratory distress syndrome (ARDS) remain areas of unmet clinical need. Preclinical studies examining mesenchymal stromal cell (MSCs) based‐therapies have provided compelling evidence of potential benefit; however, the precise mechanism by which MSCs exert a therapeutic influence, and whether MSC application is efficacious in humans, remains unknown. Detailed evaluation of the limited number of human trials so far completed is further hampered as a result of variations in trial design and biomarker selection. This review provides a concise summary of current preclinical and clinical knowledge of MSCs as a cell therapy for sepsis syndrome and ARDS. The challenges of modeling such heterogeneous and rapidly progressive disease states are considered and we discuss how lessons from previous studies of pharmacological treatments for sepsis syndrome and ARDS might be used to inform and refine the design of the next generation of MSC clinical trials. Stem Cells Translational Medicine 2017;6:1141–1151

Intravenous Infusion of Human Adipose Mesenchymal Stem Cells Modifies the Host Response to Lipopolysaccharide in Humans: A Randomized, Single-Blind, Parallel Group, Placebo Controlled Trial

“…Ample preclinical evidence indicates that MSCs can be an effective adjunctive therapy in patients with sepsis or noninfectious critical illness . A recent meta‐analysis including 20 controlled experiments in preclinical sepsis models reported that treatment with MSCs reduced the odds of mortality of experimental sepsis by approximately 73% over a range of investigational conditions .…”

“…At a high dose (4 × 10 6 cells/kg), ASCs had clear signs of biological activity, exerting a variety of proinflammatory, anti‐inflammatory, and procoagulant effects during human endotoxemia. Notably, while many previous studies examined the effect of MSCs in inflammation and sepsis models in animals , this investigation is the first to study the effect of MSCs on inflammatory responses in humans.…”

“…MSCs are now tested as a potential adjunctive therapy in inflammatory diseases including sepsis and acute respiratory distress syndrome (http://clinicaltrials.gov identifiers NCT02883803) . While the immune modulatory effects of MSCs have been studied in a variety of animal models of inflammation and infection , the current investigation is the first to report on the effects of MSCs in humans, using a well‐established model of systemic inflammation induced by intravenous injection of LPS. Our results indicate that in this transient condition of mild inflammation intravenous infusion of allogeneic ASCs was safe and exerted a variety of time‐dependent proinflammatory and anti‐inflammatory effects, as well as procoagulant features.…”

“…As such, there is a need for newer therapeutic approaches. Adult mesenchymal stem cells (MSCs) could potentially have clinical relevance in this context .…”

Mesenchymal stem/stromal cells: the therapeutic effects in animal models of acute pulmonary diseases

“…Johnson et al stated that cell therapy was commonly performed before or at the time of infection in the designed models to evaluate the effect of stem/stromal cells on damage and this is not suitable for most septic patients [75]. The results also show that the experimental model of the acute pulmonary inflammation peaks after infusion of infectious agents at 24-48 h. Accordingly, in a study by Mokhber Dezfouli et al, transplantation of stem/stromal cell was performed 24 h after inflammation with maximal inflammatory symptoms, in contrast to most of the studies that have performed stem/stromal cell transplantation between 30 min and 4 h after inflammation.…”