Cellular Immunotherapy for Septic Shock. A Phase I Clinical Trial
Abstract Rationale In septic animal models mesenchymal stem (stromal) cells (MSCs) modulate inflammation, enhance tissue repair and pathogen clearance, and reduce death. Objectives To conduct a phase I dose escalation trial of MSCs in septic shock with the primary objective of examining the safety and tolerability of MSCs. Methods We enrolled nine participants within 24 hours of admission to the ICU. A control cohort of 21 participants was enrolled before starting the MSC interventional cohort to characterize expected adverse events (AEs) and to serve as a comparator for the intervention cohort. Three separate MSC dose cohorts, with three participants per cohort, received a single intravenous dose of 0.3, 1.0, and 3.0 × 106 cells/kg. A prespecified safety plan monitored participants for the occurrence of AEs; cytokines were collected at prespecified time points. Measurements and Main Results Ages of participants in the interventional versus observational cohorts were median of 71 (range, 38–91) and 61 (range, 23–95). Acute Physiology and Chronic Health Evaluation scores were median of 25 (range, 11–28) and 26 (range, 17–32). MSC doses ranged from 19 to 250 million cells. There were no prespecified MSC infusion–associated or serious unexpected AEs, nor any safety or efficacy signals for the expected AEs or the measured cytokines between the interventional and observational cohorts. Conclusions The infusion of freshly cultured allogenic bone marrow–derived MSCs, up to a dose of 3 million cells/kg (250 million cells), into participants with septic shock seems safe. Clinical trial registered with www.clinicaltrials.gov (NCT02421484).