Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips

被引:496
作者
Homan, Kimberly A. [1 ,2 ]
Kolesky, David B. [1 ]
Skylar-Scott, Mark A. [1 ]
Herrmann, Jessica [1 ]
Obuobi, Humphrey [1 ]
Moisan, Annie [2 ]
Lewis, Jennifer A. [1 ]
机构
[1] Harvard Univ, Wyss Inst Biol Inspired Engn, Sch Engn & Appl Sci, Cambridge, MA 02138 USA
[2] Roche Innovat Ctr, Roche Pharma Res & Early Dev, Pharmaceut Sci, Basel, Switzerland
基金
美国国家科学基金会;
关键词
IN-VITRO; EXTRACELLULAR-MATRIX; EPITHELIAL-CELLS; KIDNEY ORGANOIDS; ALBUMIN; MODEL; PERFORMANCE; TRANSPORT; DISEASE; IMPACT;
D O I
10.1038/srep34845
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Three-dimensional models of kidney tissue that recapitulate human responses are needed for drug screening, disease modeling, and, ultimately, kidney organ engineering. Here, we report a bioprinting method for creating 3D human renal proximal tubules in vitro that are fully embedded within an extracellular matrix and housed in perfusable tissue chips, allowing them to be maintained for greater than two months. Their convoluted tubular architecture is circumscribed by proximal tubule epithelial cells and actively perfused through the open lumen. These engineered 3D proximal tubules on chip exhibit significantly enhanced epithelial morphology and functional properties relative to the same cells grown on 2D controls with or without perfusion. Upon introducing the nephrotoxin, Cyclosporine A, the epithelial barrier is disrupted in a dose-dependent manner. Our bioprinting method provides a new route for programmably fabricating advanced human kidney tissue models on demand.
引用
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页数:13
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