Intravenous administration of umbilical cord lining stem cells in left ventricular assist device recipients: Results of the uSTOP LVAD BLEED pilot study.

Background: Left ventricular assist device (LVAD) implantation improves survival in advanced heart failure. Despite this, angiodysplastic bleeding complications remain a significant driver of costs as well as morbidity. Mechanisms implicated in post-LVAD implant bleeding include the dysregulation of angiogenic factors seen in this population. The present pilot study evaluates the safety of umbilical cord lining stem cells (ULSCs) in LVAD recipients while exploring any early evidence of efficacy to improve bleeding. Methods: In a 3 + 3 design, 9 patients received an intravenous (IV) infusion of ULSCs at escalating doses. The primary endpoint was safety and tolerability, secondary exploratory outcomes included antibodies against hemoglobin to quantify the amount of blood in stool without the need for dietary restriction. Results: The primary safety and tolerability outcomes were met as no infusion-related adverse events or toxic responses were observed. There was no sensitization after administration of ULSCs as assessed by panel reactive antibody. An increase in angiopoietin-1 levels and a decrease in angiopoietin-2 levels from baseline to 30 days were observed in 4 patients. Quantitative Faecal Immunochemical Test suggested a decrease in the mean blood content of stool from baseline to 30 days. Conclusions: In this first-ever IV administration of ULSCs in LVAD patients, infusion was noted to be safe and tolerable and did not cause immune sensitization. Half of the patients were noted to have angiogenic stabilization, and there was a trend toward decreasing amounts of blood noted in the stool, suggesting an early signal of efficacy.