Year 2

Cardiovascular disease is the leading cause of morbidity and mortality in the United States. As humans lack the ability to regenerate myocardial tissue lost afte a heart attcak, there has been great focus on cardiovascualr regenerative therapies with the use of human embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC). There has been increased attention towards developing tissue engineering as a method to standardize methods to differentiate human ESCs and iPSCs into cardiovascular progenitor cells (CPC) expand these progenitor cells in a standardized manor. We have focused on developing techniques to allow expansion of these CPCs into clinically relevany numbers by determining: 1. Conditions to optimize their derivation into clinically numbers using clinical grade techniques.
2. Defininy and optimizing the extracellular matrxi to be used to maintain these CPCs in an undifferentiated state to allow their expansion to clinically required numbers. We studied the endogenous environment that these CPCs exist in fetal development and focused on the extracellular matrix proteins that help support these CPCs during development. By studying the array of proteins endogenously in developing heart we now will shift our focus on re-engineering this environment in-vitro to be able to mimic this growth to use this as a mean to grow and expand these progenitors for use clinically in the future. Currently we are deriving these CPCs from human ESC and iPSC and expanding them on different combinations of proteins as determined in the staining of the endogenous fetal environment. We hope to by the end of this porject determine the ideal conditions for derivation of these CPCs from iPSCs and the environmental cues needed for culturing these cells to allow for maximal yield for potential use in clinical regenerative therapies in the future.