Engineering of Pulsatile Conduits from Human Pluripotent Stem Cell-Derived Cardiomyocytes
Abstract
The Fiscal Year 2015 Peer Reviewed Medical Research Program Topic Area under which the application is submitted is "Congenital Heart Disease." Congenital heart defects are problems with the heart s structure that are present at birth and are the most common type of birth defect. Each year, more than 35,000 babies in the United States are born with congenital heart defects. Single ventricle anomalies are one of the congenital heart defects, affecting approximately 1 in 1000 live births. A child with a single ventricle defect is born with a heart with only one ventricle that pumps the blood to both pulmonary and systemic circulations, leading to the mixture of oxygenated and deoxygenated blood and ventricular volume overload. Children born with these defects have a 70% mortality rate if there is no appropriate surgical intervention. The medical interventions require series of operations; the typical one is the modified-Fontan procedure. This operation often needs to use a synthetic vascular conduit or a tissue engineered vascular conduit. Although this surgical procedure has markedly increased patient survival, synthetic or engineered vascular conduits employed lack pumping ability and thereby result in insufficient blood flow to tissues, heart failure, and pulmonary vascular diseases in these patients. Thus, there is an urgent need of a pulsatile tissue engineered conduit that can generate enough pressure to pump blood into lung. The discovery of human induced pluripotent stem cells (hiPSCs) has revolutionized stem cell research. hiPSCs resemble human embryonic stem cells (hESCs) and have potential therapeutic uses, while avoiding the ethical controversies of using human embryo. In addition, hiPSC can also be directed into any cell type of the body. As they are derived from a person s own somatic cells, such as skin fibroblasts, they do not illicit immunogenic response and can be used to generate autologous tissue engineered grafts. The current project proposes is to use cardiomyocytes (cardiac cells in the heart) derived from hiPSCs to construct tissue-engineered pulsatile conduits (TEPCs). The hiPSC-derived cardiomyocytes have the potential to generate patient specific autologous TEPCs. The TEPCs initially will be implanted as inferior vena cava interposition grafts in nude rats to test their feasibility. This would be a pilot study to generate important data for future clinical application of hiPSC-derived TEPC. There are many stem cell scientists throughout the United States who pursue tissue engineered grafts or seek for the therapeutic strategy of single ventricle cardiac defect, and the Principal Investigator will be happy to share the discoveries with them in order to facilitate their research.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610101
Entities
People
- Yibing Qyang
Organizations
- United States Army
- Yale University