Autologous Valve Replacement—CD133+Stem Cell-Plus-Fibrin Composite-Based Sprayed Cell Seeding for Intraoperative Heart Valve Tissue Engineering

Objective:The development of biological valve prostheses with lifetime native-like performance and optimal host engraftment is an ultimate goal of heart valve tissue engineering. We describe a new concept for autologous graft coating based on a CD133+-stem-cells-plus-fibrin (SC+F) complex processed from bone marrow and peripheral blood of a single patient.Methods:CD133+-SC (1 × 106cells/mL) from human bone marrow and autologous fibrin (20 mg/mL) were administered simultaneously via spray administration using the novel Vivostat Co-Delivery System. During static cultivation, SC+F performance was monitored for 20 days after delivery and compared with controls. For dynamic testing SC+F-composite was sprayed on a decellularized porcine pulmonary valve and transferred to a bioreactor under pulsatile flow conditions for 7 days.Results:Static cultivation of SC+F-composite induced significant improvements in stem cell proliferation as compared with controls. For dynamic testing, microscopic analyses on a smooth engineered heart valve surface detected homogenous distribution of stem cells. Ultrasonic analysis revealed native-like valve performance. Applied CD133+stem cells differentiated into endothelial-like cells positive for CD31 and vascular endothelial growth factor receptor 2 and engrafted the valve. However, occasional delamination was observed.Conclusion:SC+F serves as an excellent autologous matrix for intraoperative tissue engineering of valve prostheses promising optimal in vivointegration. However, stability remains an issue.