Heart and kidney organoids maintain organ-specific function in a microfluidic system

被引:17
作者
Gabbin, Beatrice [1 ]
Meraviglia, Viviana [1 ]
Angenent, Maricke L. [1 ]
Ward-van Oostwaard, Dorien [1 ]
Sol, Wendy [2 ,4 ]
Mummery, Christine L. [1 ,3 ]
Rabelink, Ton J. [2 ,4 ]
van Meer, Berend J. [1 ]
van den Berg, Cathelijne W. [2 ,4 ]
Bellin, Milena [1 ,5 ,6 ]
机构
[1] Leiden Univ, Med Ctr, Dept Anat & Embryol, Leiden, Netherlands
[2] Leiden Univ, Einthoven Lab Vasc & Regenerat Med, Med Ctr, Leiden, Netherlands
[3] Univ Twente, Dept Appl Stem Cell Technol, Enschede, Netherlands
[4] Leiden Univ, Med Ctr, Dept Internal Med Nephrol, Leiden, Netherlands
[5] Univ Padua, Dept Biol, Padua, Italy
[6] Veneto Inst Mol Med, Padua, Italy
基金
欧洲研究理事会;
关键词
Cardiac microtissues; Kidney organoids; Microfluidics; Organ-on-a-chip; Cardiorenal disease; Multi-organ in vitro system; CARDIOMYOCYTE; MATURATION; REVEAL;
D O I
10.1016/j.mtbio.2023.100818
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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. 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.
引用
收藏
页数:9
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