CIRM Intern: Tony Tam
Stem Cell Internship Lab: Mark Skylar-Scott Lab, Stanford Medicine
Project Title: Fusion of Cardiac Organoids under the Presence of Growth Factors
Abstract: There is a critical shortage of available donor organs for transplantation. For example, in the United States alone, it is estimated that only 40% of patients on the heart transplant waitlist receive a donor heart in any given year. 3D bioprinting is a promising solution to alleviate the shortage of donor organs. However, there are several roadblocks to engineering solid tissue organs, one of which is ensuring that printed tissues are morphologically and functionally similar to the organ it is intended to replace. For cardiac tissue, to generate long-range contraction, cardiomyocytes must align, and form intercalated discs for mechanical integrity and gap junctions for electrical signaling. However, bioprinted tissues are often composed of distinct cells or organoids (aggregates of differentiated cells), that lack the cell-cell connections required for long-range function, which is a major impediment to engineering functional tissues. Here, we explore biochemical methods to enhance the fusion rate of cardiac organoids by screening a panel of several compounds, including vascular endothelial growth factor (VEGF-A), epithelial growth factor (EGF), platelet-derived growth factor-beta (PDGF-B), and neuregulin-1 (NRG-1). We find the addition of EGF, and PDGF-B caused significant reduction in the area of the merged product within 3 days, while VEGF-A and NRG-1 promoted a slight reduction within the same timeframe. Using the GCaMP fluorescent reporter line, we also found that there was synchronous cardiac conduction within 3 days for EGF and PDGF growth factors, but VEGF and NRG-1 were still asynchronous. Taken together, our results suggest that EGF and PDGF-B addition can be used to enhance fusion of printed tissues consisting of cardiac organoids.
