Engineered kidneys: principles, progress, and prospects

J. Davies, C-Hong Chang, Melanie L. Lawrence, Christopher G Mills, J. Mullins
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引用次数: 8

Abstract

There is an urgent need for new ways to treat end-stage renal disease: by promoting regeneration in situ, by repopulating decellularized donor organs with a patient's own stem cells, or by making entirely new kidneys. There are two broad strategies for making new kidneys: precision engineering by positioning everything exactly – for example, by 3D printing – or supporting cells’ self-organizing ability. We describe the latter approach, which begins with a suspension of renogenic stem cells and produces a small kidney with nephrons, a collecting duct system, active transport, and an ability to integrate with host vasculature. Many problems have to be solved before these kidneys are directly clinically useful, including size, maturation, provision of a ureter, and production from human-induced pluripotent stem cells. Even the existing engineered kidneys, if they can be made from human rather than animal cells, may be useful for assays for adverse drug reactions that will be free of the problems of extrapolating from animal tests to predicted human responses.
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工程肾脏:原理、进展与展望
迫切需要治疗终末期肾病的新方法:通过促进原位再生,用患者自己的干细胞重新填充去细胞化的供体器官,或制造全新的肾脏。制造新肾脏有两种广泛的策略:通过精确定位所有东西的精密工程——例如,通过3D打印——或者支持细胞的自组织能力。我们描述了后一种方法,它从肾原干细胞的悬浮开始,产生一个具有肾单位、收集管系统、主动运输和与宿主脉管系统整合能力的小肾脏。在这些肾脏直接用于临床之前,有许多问题需要解决,包括大小、成熟、输尿管的提供以及人类诱导的多能干细胞的产生。即使是现有的工程肾脏,如果它们可以由人类而不是动物细胞制成,也可能对药物不良反应的分析有用,从而避免从动物试验中推断出预测人类反应的问题。
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