PROJECT SUMMARY
Ischemic heart disease is a leading cause of morbidity and mortality worldwide. The lost cardiomyocytes are
replaced with fibrous scar tissue, which leads to maladaptive remodeling, contractile dysfunction, and progresses
to congestive heart failure. Stem cell transplantation offers a great potential to repair and possibly regenerate
damaged myocardium, thus multiple adult stem/progenitors have been explored. However, the critical barriers
in stem cell therapy for cardiac regeneration are the lack of long-term survival, insufficient maturation, and
unsuccessful coupling and alignment of grafted cardiomyocytes to the host tissue. This project aims to address
these critical limitations through integration of genetically engineered stem cells and electrically conductive
nanoengineered hydrogel biomaterials. Specifically, we will develop human engineered heart tissues (EHTs)
and explore a new therapeutic approach which leverages the capacity of gold nanorods (GNRs) and hydrogel
micro-topographies to induce electrical conductivity, cell maturation and alignment within the EHTs. In addition,
we will take the advantage of our recently established techniques to induce proliferation and survival
cardiomyocytes within the EHTs. Furthermore, we will investigate whether co-culture of isogenic human induced
pluripotent stem cells (hiPSCs)-derived cardiomyocytes (hiPSCs-CMs), endothelial cells (hiPSCs-ECs), smooth
muscle cells (hiPSCs-SMCs), and cardiac fibroblasts (hiPSCs-CFs) within the engineered heart tissue promote
angiogenesis, engraftment and tissue contractility. Moreover, the efficacy and safety of these novel EHTs,
developed in this project, will be evaluated in the preclinical acute rat and chronic pig models of ischemic heart
disease, which could potentially aid in clinical trials in treating MI patients.
