Clinical Application of Tissue Engineered Human Heart Valves Using Autologous Progenitor Cells

Abstract

Background-Tissue engineering (TE) of heart valves reseeded with autologous cells has been successfully performed in vitro. Here, we report our first clinical implantation of pulmonary heart valves (PV) engineered with autologous endothelial progenitor cells (EPCs) and the results of 3.5 years of follow-up. Methods and Results-Human PV allografts were decellularized (Trypsin/EDTA) and resulting scaffolds reseeded with peripheral mononuclear cells isolated from human blood. Positive stain for von Willebrand factor, CD31, and Flk-1 was observed in monolayers of cells cultivated and differentiated on the luminal surface of the scaffolds in a dynamic bioreactor system for up to 21 days, indicating endothelial nature. PV reseeded with autologous cells were implanted into 2 pediatric patients (age 13 and 11) with congenital PV failure. Postoperatively, a mild pulmonary regurgitation was documented in both children. Based on regular echocardiographic investigations, hemodynamic parameters and cardiac morphology changed in 3.5 years as follows: increase of the PV annulus diameter (18 to 22.5 mm and 22 to 26 mm, respectively), decrease of valve regurgitation (trivial/mild and trivial, respectively), decrease (16 to 9 mm Hg) or a increase (8 to 9.5 mm Hg) of mean transvalvular gradient, remained 26 mm or decreased (32 to 28 mm) right-ventricular end-diastolic diameter. The body surface area increased (1.07 to 1.42 m 2 and 1.07 to 1.46 m 2 , respectively). No signs of valve degeneration were observed in both patients. Conclusions-TE of human heart valves using autologous EPC is a feasible and safe method for pulmonary valve replacement. TE valves have the potential to remodel and grow accordingly to the somatic growth of the child.

Avaliação do comportamento biológico de homoenxertos valvares pulmonares descelularizados: estudo experimental em ovinos

“…As in our study, the authors show that the decellularized heterografts showed a significant increase in their diameter valves, unlike conventional cryopreserved homografts, which have maintained their original diameter. Cebotari et al [36] reconstructed the RVOT of children with homografts decellularized with trypsin-EDTA and seeded in vitro with autologous endothelial cells, and also showed an increase in the diameter of these grafts after three years of follow-up with the maintenance of low gradients and valve competence, suggesting the remodeling and growth.…”

Emprego e avaliação em médio prazo da cúspide de homoenxerto decelularizado na correção da tetralogia de Fallot

“…Apart from the current methodology, the aim is to obtain an acellular tissue without damaging the components of the extracellular matrix, such as collagen and elastic fibers, as well as to keep macromolecules proportions intact. Thus, the purpose is to obtain an immunologically inert matrix with preserved biomechanical properties that is noncytotoxic and totally biocompatible [20][21].…”

Passive and active contributions to generated force and retraction in heart valve tissue engineering

“…Implantation of a decellularized valve would represent a different approach, as it would require seeding of new non-contractile cells or the attraction of endogenous cells in vivo to ensure a viable implant. It is, however, a promising approach as decellularized valves have already shown functionality in vivo (Simon et al 2003;Cebotari et al 2006;Erdbrugger et al 2006;Hopkins et al 2009) and it is currently under investigation for tissue engineered constructs as well (Dahl et al 2011).…”