Cellular Immunotherapy for Septic Shock A Phase I Clinical Trial

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 x 10(6) 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.