Abstract

Superior Proangiogenic Characteristics of Human Neonatal Thymus Mesenchymal Stem Cells

Ming-Sing Si, Assistant Professor, University of Michigan

Newborns with congenital heart disease who undergo cardiac surgery already have or are at risk of developing conditions related to inadequate myocardial perfusion. We have recently discovered that MSCs isolated from discarded thymus tissue from neonates undergoing cardiac surgery are proangiogenic. The objective here was to assess the therapeutic potential of thymus MSCs (tMSCs) by comparing their proangiogenic characteristics to those of bone derived MSCs. In an initial comparison to adult bone marrow MSCs, we found that tMSCs were superior in promoting EC migration and spheroid sprouting. We then demonstrated that tMSCs were superior in promoting the formation of human neovessels in a subcutaneous implant model in immunodeficient mice. To account for age, we performed a patient-matched in vitro comparison using sternal bone derived MSCs. We found that tMSCs were superior to matched bone MSCs in promoting angiogenesis in vitro. A genome-wide, patient-matched comparison demonstrated a significant increase in SLIT3 expression in tMSCs. The proangiogenic properties of tMSCs were blocked in vitro by soluble ROBO4 and SLIT3 siRNA. These data indicate that discarded thymus tissue is a relevant source of proangiogenic SLIT3 expressing MSCs. Evaluation of tMSCs in cardiovascular disease models is ongoing. We have discovered that MSCs isolated from discarded thymus tissue obtained during neonatal open heart surgery possess potent therapeutic properties, thus making them a candidate for use as cell therapy in these young patients with limited treatment options.