Safety of Intracoronary Human Cord Blood Stem?Cells in a Lamb Model of Infant Cardiopulmonary Bypass

摘要

CBMNC DosageAnimals and Surgical ProcedureExperimental ProtocolStatistical AnalysisResultsCBMNC-Cardioplegia Cell ViabilityHemodynamics and Cardiac FunctionDetection of Circulating Human CD45+ CellsVascular Patency and Tissue Distribution of Human CD45+ CellsCommentSupplementary DataReferencesOne potential approach for advancing univentricular heart surgical palliation outcomes is by stem cell therapy to augment right ventricular function and muscle mass. Whether the stem cell–inclusive cord blood mononuclear cells (CBMNCs) are safe to perfuse into the coronary vasculature during neonatal cardiopulmonary bypass (CPB) is unknown. We evaluated the acute safety, functional effects, and fate of human CBMNCs in a novel model of coronary vasculature delivery in a lamb model of infant CPB.MethodsNeonatal lambs were randomized in blinded fashion to receive control (n?= 5) or human CD45+ CBMNCs (8?× 106 cells/kg body weight, n?= 7) treatments during CPB. Aortic cross-clamp time was 40 minutes, with maintenance blood cardioplegia delivered every 10 minutes. Pressure-volume indices were used to measure left ventricular function before CPB and 60 minutes after CPB. CBMNCs were assessed by flow cytometry and immunohistochemistry.ResultsCBMNC-treated lambs were hemodynamically stable after CPB, with a decline in left ventricular pressure-volume indices similar to controls. The coronary vasculature was patent on microscopy, without evidence of cell aggregates or clots. Human CD45+ cells were distributed in high abundance within all cardiac regions, predominantly the right atrium and ventricles, and trafficked beyond endothelial cell layers and between myocytes. CD45+ cells localized at low incidence in the spleen, liver, lungs, and kidneys, but rarely remained in the circulation (<0.1% of infused cells).ConclusionsCoronary delivery of human CBMNCs during blood-cardioplegic arrest in a lamb model of CPB results in highly abundant myocardial distribution of cells without acute adverse effects on vascular patency and post-CPB cardiac function.The AppendicesAppendices can be viewed in the online version of this article [http://dx.doi.org/10.1016/j.athoracsur.2015.04.130] on http://www.annalsthoracicsurgery.com.Although the surgical innovation of recent decades has enabled a remarkable increase in survival outcomes after surgical palliation of univentricular conditions such as hypoplastic left heart syndrome (HLHS) [