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Characterisation and evaluation of cell phenotype and extracellular matrix in tissue engineering heart valves based on human cardio-vascular cells

English title Charakterisierung und Evaluation von Zellphenotyp and Extrazellulärer Matrix in Tissue Engineering Herzklappen basierend auf humanen kardiovaskulären Zellen
Applicant Hoerstrup Simon Philipp
Number 101116
Funding scheme NRP 46 Implants and Transplants
Research institution Klinik für Infektionskrankheiten und Spitalhygiene Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Biomedical Engineering
Start/End 01.06.2003 - 31.05.2005
Approved amount 254'948.00
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Lay Summary (English)

Lead
Lay summary
Characterization and Evaluation of Cell Phenotype and Extracellular Matrix in Tissue Engineered Heart Valves Based on Human Cardiovascular Cells

Background
Based on a novel "biomimetic" (pulse-duplicator) in vitro-environment we have been able to demonstrate the principal feasibility of tissue engineered living, completely autologous heart valves. These tissue engineered heart valves showed excellent functional in vivo-performance in long-term animal experiments. The tissue engineered heart valves were based on ovine vascular derived myofibroblasts and endothelial cells and gradually evolved to resemble native valves as to extracellular matrix and cell composition.

Objective
The aim of this study is to define "quality criteria" for a near future clinical application of tissue engineered heart valves as to human cellular and matrix characteristic to provide maximum safety for the cardiac surgery patients. Accordingly, the objective of this project is to investigate cell phenotype, immunology and matrix maturation processes in tissue engineered heart valves based on human cells and grown in biomimetic in vitro-conditions. A meticulous understanding of the developmental biology during the multi-step engineering procedure is a prerequisite to safe transferral of the tissue engineering concept to human applications. The following specific aims will be addressed:

Aim 1: Characterization of human myofibroblast cell phenotype during the in vitro-tissue evolution of human tissue engineered heart valves. Study of the influence of biomimetic in vitro-conditions and cell donor age.

Aim 2: Investigation of extracellular matrix composition, maturation, and biomechanical properties in tissue engineered heart valves based on human myofibroblasts with specific focus on the influence of physiological in vitro-conditions and cell donor age.

Aim 3: Determine the phenotype, immunological and functional potential of human endothelial cells used for tissue engineered heart valves evaluated in pulsatile and non-pulsatile in vitro-conditions.

Approach
Prior to clinical application it is crucial for researchers and clinicians to have reliable "quality criteria" of tissue engineered heart valves regarding adequate cell differentiation, sufficient extracellular matrix maturation, and the absence of detrimental immunogenic characteristics. "Benchmark" for the definition of these criteria is human native heart valve tissue. Therefore, the results of this research plan may represent a concrete step towards the first successful clinical application of a human autologous tissue engineered heart valve.<
Direct link to Lay Summary Last update: 21.02.2013

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