Cellular Immunotherapy for Septic Shock. A Phase I Clinical Trial

TLDR

Mesenchymal stem cells modulate inflammation, enhance tissue repair and pathogen clearance, and reduce mortality in septic animal models. The study aimed to evaluate the safety and tolerability of MSCs in septic shock through a phase I dose‑escalation trial. The trial enrolled nine septic shock patients in a dose‑escalation design (0.3, 1.0, 3.0 × 10⁶ cells/kg) with a preceding observational cohort of 21 patients to characterize expected adverse events, monitoring safety and cytokine profiles at predefined time points. No infusion‑related or serious adverse events were observed, and cytokine profiles did not differ between MSC‑treated and observational groups, indicating that allogenic MSCs up to 3 million cells/kg are safe in septic shock. Clinical trial registered at ClinicalTrials.gov (NCT02421484).

Abstract

In septic animal models mesenchymal stem (stromal) cells (MSCs) modulate inflammation, enhance tissue repair and pathogen clearance, and reduce death.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.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.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.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).