Abstract
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.
Highlights
Kidney organoids are emerged in recent years in a pre-clinical, post-approval stage of the pharmaceutical development [1]
We developed a kidney organoid-on-achip system to demonstrate the effect of extracellular matrix (ECM) and fluidic shear stress on in vitro development of human pluripotent stem cells (hPSCs)-derived human kidney organoids
4 Conclusions We developed a kidney organoid-on-a-chip to enable the control of the blood vessel differentiation of a kidney organoid
Summary
Kidney organoids are emerged in recent years in a pre-clinical, post-approval stage of the pharmaceutical development [1]. The human pluripotent stem cells (hPSCs)-derived human kidney organoid is a novel method of a three-dimensional (3D) culture in vitro model for drug screening applications. Under appropriate induction (e.g., growth factor treatment), the stem cells could differentiate into the specific kidney cell lineages. The stem cell-induced kidney organoids have the Despite the great potential of the human kidney organoids, the kidney organoids are functionally immature and anatomically different from in vivo human tissues at a current stage. The major concerns about the generation of kidney organoids from hPSCs are the lack of the vascularization which still limits the growth and maturation of the organoids [6]. Most cells cannot survive when located more than 200 μm away from a blood vessel due to the limited
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