Effect of biochemical and biomechanical factors on vascularization of kidney organoid-on-a-chip

Kidney organoids derived from the human pluripotent stem cells (hPSCs) recapitulating human kidney are the attractive tool for kidney regeneration, disease modeling, and drug screening. However, the kidney organoids cultured by static conditions have the limited vascular networks and immature nephron-like structures unlike human kidney. Here, we developed a kidney organoid-on-a-chip system providing fluidic flow mimicking shear stress with optimized extracellular matrix (ECM) conditions. We demonstrated that the kidney organoids cultured in our microfluidic system showed more matured podocytes and vascular structures as compared to the static culture condition. Additionally, the kidney organoids cultured in microfluidic systems showed higher sensitivity to nephrotoxic drugs as compared with those cultured in static conditions. We also demonstrated that the physiological flow played an important role in maintaining a number of physiological functions of kidney organoids. Therefore, our kidney organoid-on-a-chip system could provide an organoid culture platform for in vitro vascularization in formation of functional three-dimensional (3D) tissues.

Automated summary

By mimicking shear stress fluid flow and optimizing extracellular matrix conditions, our kidney organoid-on-a-chip system showed more mature podocytes and vascular structures compared to static culture, with increased sensitivity to nephrotoxic drugs. Physiological flow was demonstrated to play a crucial role in maintaining various physiological functions of kidney organoids.