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生化和生物力学因素对芯片上肾类器官血管化的影响。

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

作者信息

Lee Han Na, Choi Yoon Young, Kim Jin Won, Lee Young Seo, Choi Ji Wook, Kang Taewook, Kim Yong Kyun, Chung Bong Guen

机构信息

Department of Biomedical Engineering, Sogang University, Seoul, South Korea.

Institute of Integrated Biotechnology, Sogang University, Seoul, South Korea.

出版信息

Nano Converg. 2021 Nov 8;8(1):35. doi: 10.1186/s40580-021-00285-4.

DOI:10.1186/s40580-021-00285-4
PMID:34748091
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8575721/
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.

摘要

源自人多能干细胞(hPSC)的类器官模拟人肾脏,是肾脏再生、疾病建模和药物筛选的有吸引力的工具。然而,与人类肾脏不同,在静态条件下培养的肾脏类器官具有有限的血管网络和不成熟的肾单位样结构。在此,我们开发了一种芯片上肾脏类器官系统,该系统提供模拟剪切应力的流体流动,并具有优化的细胞外基质(ECM)条件。我们证明,与静态培养条件相比,在我们的微流控系统中培养的肾脏类器官显示出更成熟的足细胞和血管结构。此外,与在静态条件下培养的肾脏类器官相比,在微流控系统中培养的肾脏类器官对肾毒性药物表现出更高的敏感性。我们还证明,生理流动在维持肾脏类器官的多种生理功能中起着重要作用。因此,我们的芯片上肾脏类器官系统可为功能性三维(3D)组织形成中的体外血管化提供类器官培养平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a668/8575721/ae4adae96f0e/40580_2021_285_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a668/8575721/a3e2e7c4b280/40580_2021_285_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a668/8575721/69948195d5f0/40580_2021_285_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a668/8575721/8c40398be973/40580_2021_285_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a668/8575721/8eea72fcd4d9/40580_2021_285_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a668/8575721/ae4adae96f0e/40580_2021_285_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a668/8575721/a3e2e7c4b280/40580_2021_285_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a668/8575721/69948195d5f0/40580_2021_285_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a668/8575721/8c40398be973/40580_2021_285_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a668/8575721/8eea72fcd4d9/40580_2021_285_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a668/8575721/ae4adae96f0e/40580_2021_285_Fig5_HTML.jpg

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