类有机物
细胞生物学
体外
功能(生物学)
生物
球体
小岛
多细胞生物
计算生物学
化学
胰岛素
内分泌学
细胞
生物化学
作者
Smit N. Patel,Matthew Ishahak,Deborah Chaimov,Ashwin Velraj,Daniel J. LaShoto,D. Walker Hagan,Péter Buchwald,Edward A. Phelps,Ashutosh Agarwal,Cherie L. Stabler
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2021-02-12
卷期号:7 (7)
被引量:58
标识
DOI:10.1126/sciadv.aba5515
摘要
Three-dimensional (3D) multicellular organoids recapitulate the native complexities of human tissue better than traditional cellular monolayers. As organoids are insufficiently supported using standard static culture, microphysiological systems (MPSs) provide a key enabling technology to maintain organoid physiology in vitro. Here, a polydimethylsiloxane-free MPS that enables continuous dynamic culture and serial in situ multiparametric assessments was leveraged to culture organoids, specifically human and rodent pancreatic islets, within a 3D alginate hydrogel. Computational modeling predicted reduced hypoxic stress and improved insulin secretion compared to static culture. Experimental validation via serial, high-content, and noninvasive assessments quantitatively confirmed that the MPS platform retained organoid viability and functionality for at least 10 days, in stark contrast to the acute decline observed overnight under static conditions. Our findings demonstrate the importance of a dynamic in vitro microenvironment for the preservation of primary organoid function and the utility of this MPS for in situ multiparametric assessment.
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