Efficacy of Mesenchymal Stromal Cell Therapy for Acute Lung Injury in Preclinical Animal Models: A Systematic Review

<div><p>The Acute Respiratory Distress Syndrome (ARDS) is a devastating clinical condition that is associated with a 30–40% risk of death, and significant long term morbidity for those who survive. Mesenchymal stromal cells (MSC) have emerged as a potential novel treatment as in pre-clinical models they have been shown to modulate inflammation (a major pathophysiological hallmark of ARDS) while enhancing bacterial clearance and reducing organ injury and death. A systematic search of MEDLINE, EMBASE, BIOSIS and Web of Science was performed to identify pre-clinical studies that examined the efficacy MSCs as compared to diseased controls for the treatment of Acute Lung Injury (ALI) (the pre-clinical correlate of human ARDS) on mortality, a clinically relevant outcome. We assessed study quality and pooled results using random effect meta-analysis. A total of 54 publications met our inclusion criteria of which 17 (21 experiments) reported mortality and were included in the meta-analysis. Treatment with MSCs, as compared to controls, significantly decreased the overall odds of death in animals with ALI (Odds Ratio 0.24, 95% Confidence Interval 0.18–0.34, I² 8%). Efficacy was maintained across different types of animal models and means of ALI induction; MSC origin, source, route of administration and preparation; and the clinical relevance of the model (timing of MSC administration, administration of fluids and or antibiotics). Reporting of standard MSC characterization for experiments that used human MSCs and risks of bias was generally poor, and although not statistically significant, a funnel plot analysis for overall mortality suggested the presence of publication bias. The results from our meta-analysis support that MSCs substantially reduce the odds of death in animal models of ALI but important reporting elements were sub optimal and limit the strength of our conclusions.</p></div

Tracking of autologous VSOP-labeled mesenchymal stem cells in the sheep brain using 3.0 T MRI

Assessment of biodistribution and monitoring of cell migration processes in vivo are essential for the safety of novel cell-based therapies for ischemic stroke and early-stage clinical trials, but are mainly lacking investigation in large animal models which are closer to the situation found in human patients. This chapter reports a series of experiments which establish a MRI-sensitive labeling procedure for autologous ovine mesenchymal stem cells (MSC) and the assessment of in vivo and in vitro detection limits of the cells at 3.0 T. Cell migration was monitored after intravenous transplantation following experimental stroke in sheep. Cell detection was feasible at 3.0 T with detection limits defined at 500 cells in vitro and 1,000 cells after local stereotaxic administration in vivo. No signs for MSC homing toward the ischemic lesion were observed after systemic cell delivery. Iron-containing cells were identified in the lung and skin wounds, but not in brain parenchyma after intravenous cell delivery. These findings are in contrast to results obtained in small animal models and may indicate significant differences of MSC behavior in large organisms. They also revealed the necessity for sensitivity-enhanced MRI sequences for improved cell detection in large animals