Enabling Ex Vivo Heart Studies on Stem Cell Differentiation, Integration, and Repair
Abstract
Cardiovascular diseases remain the leading causes of death, affecting one in three adults
worldwide. The most common form of cardiovascular disease is the coronary heart disease
(CHD)[1], which can lead to a myocardial infarction (MI), or heart attack. The heart does not
contain a significant pool of endogenous stem cells for intrinsic regeneration and is, therefore,
incapable of repairing itself. Stem cell therapy can potentially improve heart function after MI;
however, it is difficult to conduct controlled studies on cell and tissue integration of in vivo MI
models. Therefore, there is a need for an ex vivo model that can help assess the survival,
differentiation, and integration of injected cells. Here, I first generate induced pluripotent stem cells
(iPSC) from a non-invasive cell source by first establishing a stable cell culture system for these
cells. I then developed a tissue-stretching device that is able to secure fragile heart tissue slices and
provide uniaxial cyclic mechanical stimulation to cardiac tissue slices that will preserve their native
physiology for up to 3 months. Tissue slices supported with device for 10 days show over 50%
improvement in cxn43 expression and display higher alignment compared with slices that are
unloaded. Lastly, I differentiated PSCs into cardiomyocyte cells and have verified that laminin and
fibronectin matrix direct high number of cardiac cells containing distinct ITGB4 and ITGB5 cell
populations. The ex vivo tissue model developed will enable longer-term studies of cell and tissue
grafting onto the heart.