Organoid models are used to study kidney physiology,such as the assessment of nephrotoxicity and underlying disease processes.Personalized human pluripotent stem cell-derived kidney organoids are ideal models for comp...Organoid models are used to study kidney physiology,such as the assessment of nephrotoxicity and underlying disease processes.Personalized human pluripotent stem cell-derived kidney organoids are ideal models for compound toxicity studies,but there is a need to accelerate basic and translational research in the field.Here,we developed an automated continuous imaging setup with the“read-on-ski”law of control to maximize temporal resolution with minimum culture plate vibration.High-accuracy performance was achieved:organoid screening and imaging were performed at a spatial resolution of 1.1µm for the entire multi-well plate under 3 min.We used the in-house developed multi-well spinning device and cisplatin-induced nephrotoxicity model to evaluate the toxicity in kidney organoids using this system.The acquired images were processed via machine learning-based classification and segmentation algorithms,and the toxicity in kidney organoids was determined with 95%accuracy.The results obtained by the automated“read-on-ski”imaging device,combined with label-free and non-invasive algorithms for detection,were verified using conventional biological procedures.Taking advantage of the close-to-in vivo-kidney organoid model,this new development opens the door for further application of scaled-up screening using organoids in basic research and drug discovery.展开更多
基金This research was funded by the Scientific Instrumentation Development Program of Chinese Academy of Sciences(No.ZDZBGCH2018005)the Key Research and Development Program of Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory)(No.2019GZR1104060)the Research Instrument and Equipment Development Project of Chinese Academy of Sciences(No.ZDKYYQ20210006),China.
文摘Organoid models are used to study kidney physiology,such as the assessment of nephrotoxicity and underlying disease processes.Personalized human pluripotent stem cell-derived kidney organoids are ideal models for compound toxicity studies,but there is a need to accelerate basic and translational research in the field.Here,we developed an automated continuous imaging setup with the“read-on-ski”law of control to maximize temporal resolution with minimum culture plate vibration.High-accuracy performance was achieved:organoid screening and imaging were performed at a spatial resolution of 1.1µm for the entire multi-well plate under 3 min.We used the in-house developed multi-well spinning device and cisplatin-induced nephrotoxicity model to evaluate the toxicity in kidney organoids using this system.The acquired images were processed via machine learning-based classification and segmentation algorithms,and the toxicity in kidney organoids was determined with 95%accuracy.The results obtained by the automated“read-on-ski”imaging device,combined with label-free and non-invasive algorithms for detection,were verified using conventional biological procedures.Taking advantage of the close-to-in vivo-kidney organoid model,this new development opens the door for further application of scaled-up screening using organoids in basic research and drug discovery.
