This PhD thesis by Ulgu Arslan titled as “hiPSC-derived 3D cardiac microphysiological systems that can integrate immune and vascular components” explores culture conditions and their effects to... Show moreThis PhD thesis by Ulgu Arslan titled as “hiPSC-derived 3D cardiac microphysiological systems that can integrate immune and vascular components” explores culture conditions and their effects to incorporate human induced pluripotent stem cell derived macrophages in 3D cardiac microtissues; and endothelial cells to form vascularized and perfusable 3D cardiac microtissues on chips. It discusses and compares current state-of-the-art 3D microphysiological models with respect to their applications, readouts, limitations and possible implementation for their future use. Then, it establishes static microtissue or perfused organ-on-chip models with an emphasis on their potential to study microenvironmental cues, cellular crosstalk, disease modelling and drug testing in cardiovascular research. Show less
Heart and kidney communicate with one another in an interdependent relationship and they influence each other's behavior reciprocally, as pathological changes in one organ can damage the other.... Show moreHeart and kidney communicate with one another in an interdependent relationship and they influence each other's behavior reciprocally, as pathological changes in one organ can damage the other. Although independent human in vitro models for heart and kidney exist, they do not capture their dynamic crosstalk. We have developed a microfluidic system which can be used to study heart and kidney interaction in vitro. Cardiac microtissues (cMTs) and kidney organoids (kOs) derived from human induced pluripotent stem cells (hiPSCs) were generated and loaded into two separated communicating chambers of a perfusion chip. Static culture conditions were compared with dynamic culture under unidirectional flow. Tissue viability was maintained for minimally 72 h under both conditions, as indicated by the presence of sarcomeric structures coupled with beating activity in cMTs and the presence of nephron structures and albumin uptake in kOs. We concluded that this system enables the study of human cardiac and kidney organoid interaction in vitro while controlling parameters like fluidic flow speed and direction. Together, this "cardiorenal-unit" provides a new in vitro model to study the cardiorenal axis and it may be further developed to investigate diseases involving both two organs and their potential treatments. Show less
