Student Shanghai Institute of Biochemistry and Cell Biology (SIBCB), China
Abstract: Three-dimensional organoid technologies have revolutionized research in human organs and diseases. However, available liver organoid systems failed to construct a perfusable vasculature and in vivo liver lobule architecture. The lack of vascular networks restricts the size of organoid and limit the multicellular communications. Here we develop a millimeter-scale vascularized liver lobule-like tissue(vLB) with a perfusable capillary by taking advantage of microfluidic chip and cellular self-assembly. In vLB, hepatocytes interacted with non-parenchymal cells, forming structures analogous to the in vivo hepatic plate and space of Disse while maintaining the functionality of hepatocytes. Endothelial cells in vLB acquired certain molecular and structural characteristics of liver sinusoidal endothelium. Based on vLB, we also integrate innate immune cells into this tissue by perfusing monocyte-derived macrophages. Macrophages reside in the vessels, in prime position to respond to any pathogens entering the vLB via the vessels. The concept of extrinsically guiding the self-organization of multiple cell types into functional vascularized tissues is broadly applicable and holds promise for achieving more physiologically relevant tissue structures and functions.
