The in vitro construction of a tissue engineered bioprosthetic heart valve

Abstract

PROBLEM: Heart valve replacement with either a nonliving xenograft or amechanical prosthesis is an effective therapy for valvular heart disease.Both of these approaches have limitations, including their inability togrow, repair, and remodel. In addition, a mechanical prosthesis requireslong-term anticoagulation therapy. METHODS: This study demonstrates the invitro creation of tissue engineered heart valve tissue using cardiovascularcells on degradable polymer matrices, 40 heart valve leaflets were createdusing this technique from two sources. Xenograft leaflets were createdusing human dermal fibroblasts and bovine aortic endothelial cells (n = 20)or allograft valve leaflets were created using sheep myofibroblasts andsheep endothelial cells (n = 20). A mixed sheep cell population wasobtained consisting of endothelial cells and myofibroblasts. Endothelialcells were labelled with acethylated low density lipoprotein (Ac-Dil-LDL)and cells were separated into two groups using an activated cell sorter:LDL positive cells comprised of a pure endothelial cell population and LDLnegative cells comprised of mixed cell population containing myofibroblastsand smooth muscle cells. The LDL negative cells were seeded on a syntheticpolyglycolic acid (PGA) mesh and grown in vitro to form a tissue-likefibroblast-mesh core. Endothelial cells were then seeded onto the surfaceof the fibroblast-mesh core, forming a single monolayer. RESULTS:Histological evaluation of these constructs revealed an inner core of LDLnegative cells and outer endothelial-like cells which were factor VIIIpositive. There was no evidence of capillary formation from endothelialcells invading the myofibroblasts and smooth muscle matrix and theendothelial lining appeared complete. CONCLUSIONS: It is feasible toconstruct allogenic heart valve tissue which could be used to make avalve.