Evolution of Cell Phenotype and Extracellular Matrix in Tissue-Engineered Heart Valves during In-Vitro Maturation and In-Vivo Remodeling
Elena Rabkin MD, Simon P. Hoerstrup MD, Masanori Aikawa MD, John E. Mayer, Jr. MD, Frederick J. Schoen MD

Contemporary tissue valves are non-viable, and unable to grow, repair or remodel. It was postulated that tissue-engineered heart valves (TEHV) yield a dynamic progression of cell phenotype and ECM, in vitro and in vivo, and ultimately recapitulate native valve. ECM composition and collagen architecture was examined by special histological staining, and cell phenotype by immunohistochemistry using TEHV prepared in vitro and implanted in vivo. Activated myofibroblasts were prominent in in-vitro constructs. Cells from in-vivo explants at 16-20 weeks were fibroblast-like (similar to native valve). ECM remodeling was evident in vitro at 14 days. Moreover, ECM architecture of 16- to 20-week TEHV resembled those of native valves. In conclusion, cell phenotype and ECM in TEHV are dynamic and reflect the ability of a vital tissue to remodel and, potentially, to grow.