Functional Kidney Bioengineering with Pluripotent Stem-Cell-Derived Renal Progenitor Cells and Decellularized Kidney Scaffolds
Functional Kidney Bioengineering with Pluripotent Stem-Cell-Derived Renal Progenitor Cells and Decellularized Kidney Scaffolds
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DOI：
10.1002/adhm.201600120
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发表时间：
2016-08-24
影响因子：
10
通讯作者：
Wan, Andrew C. A.
中科院分区：
文献类型：
--
作者：
Du, Chan;Narayanan, Karthikeyan;Wan, Andrew C. A.
发育生物学和干细胞技术的最新进展导致了在培养皿中进行功能器官的工程化。然而，这些类器官的有限大小和缺乏大型循环系统对其临床转化构成了限制。为了克服这些问题，使用人诱导多能干细胞衍生的肾祖细胞和内皮细胞，将具有天然微结构和细胞外基质（ECM）的脱细胞全肾支架用于肾脏生物工程。为了证明ECM引导的细胞组装，目前的工作集中在产生肾脏的功能单位，肾小球。在再生器官中，内皮细胞的存在广泛上调了与肾脏发育相关的基因的表达水平。当将细胞化的天然支架植入SCID小鼠中时，可以通过肾祖细胞和内皮细胞的共培养来实现肾小球组装。这些单独的肾小球单位被证明是功能性的，在整个器官的背景下，使用模拟的生物反应器设置与尿素和肌酐排泄和白蛋白重吸收。我们的研究结果表明，使用临床相关的，可扩展的患者特异性肾祖细胞和内皮细胞的脱细胞天然肾的再增殖可能是一种可行的方法，用于产生功能完整的肾脏。
Recent advances in developmental biology and stem cell technology have led to the engineering of functional organs in a dish. However, the limited size of these organoids and absence of a large circulatory system poses limits to its clinical translation. To overcome these issues, decellularized whole kidney scaffolds with native microstructure and extracellular matrix (ECM) are employed for kidney bioengineering, using human-induced pluripotent-stem-cell-derived renal progenitor cells and endothelial cells. To demonstrate ECM-guided cellular assembly, the present work is focused on generating the functional unit of the kidney, the glomerulus. In the repopulated organ, the presence of endothelial cells broadly upregulates the expression level of genes related to renal development. When the cellularized native scaffolds are implanted in SCID mice, glomeruli assembly can be achieved by co-culture of the renal progenitors and endothelial cells. These individual glomerular units are shown to be functional in the context of the whole organ using a simulated bio-reactor set-up with urea and creatinine excretion and albumin reabsorption. Our results indicate that the repopulation of decellularized native kidney using clinically relevant, expandable patient-specific renal progenitors and endothelial cells may be a viable approach for the generation of a functional whole kidney.