Engineered Heart Slices
While cardiomyocytes derived from stem cells represent a promising tool for studies of human cardiac biology, their immature structure and function does not reflect post-natal cardiac tissue. Because of this, new strategies are needed to advance cardiomyocyte maturation and build tissue-like systems for study. To this end, we created an engineered cardiac preparation by repopulating sections of decellularized myocardium with human stem cell-derived cardiomyocytes. This resulted in tissue-like platform with aligned, mature cardiomyocytes that could be cultured for hundreds of days, exhibited anisotropic conduction of action potentials, and responded physiologically to cardiac channel blockers. This work contributes to the development of mature cardiac tissues from stem cell sources that can be used in patient-specific cardiac studies and drug screens.
Microvascular Networks with Flow
The function of blood vessels in the body is tightly regulated by hemodynamic forces generated by blood flow. In order to study the mechanisms by which these forces regulate vascular biology, vascular models must incorporate physiological flows. To build such a model, we formed microvascular networks within a microfluidic device from endothelial cells containing a cellular flow sensor. Using an on-chip pump, these networks were subjected to laminar flow to induce fluorescence driven by the expression of KLF2, a flow-regulated transcription factor. We found that application of flow increased vessel diameter and decreased vascular resistance, branching, and morphological variability. Additionally, flow decreased vascular permeability and decreased blood clot formation in the vessels. This microfluidic system can be used to study physiological mechanisms in microvasculature that are regulated by flow.
Vascularized Heart-on-a-Chip
Organ-on-a-chip technology has been utilized to model a variety of physiological systems and represents a promising platform for pre-clinical studies. However, vascularizing organoids has been a major technical challenge in the field. We are developing a method for forming a vascularized heart-on-a-chip by integrating cardiac organoids with surrounding microvasculature within a microfluidic device. Our approach yields a fully perfusable system that can be used to study the crosstalk between cardiomyocytes and vasculature, especially in the context of changes in fluid flow and contraction.