Design and strategy for manufacturing kidney organoids
Design and strategy for manufacturing kidney organoids
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DOI：
10.1007/s42242-020-00060-0
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发表时间：
2020-03
影响因子：
7.9
通讯作者：
M. Nishikawa;Y. Sakai;N. Yanagawa
中科院分区：
文献类型：
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作者：
M. Nishikawa;Y. Sakai;N. Yanagawa
尽管患有慢性肾病的患者数量持续增加，但目前可用于这些患者的治疗，如透析和肾移植，是不完善的。肾脏也是易受各种新药毒性影响的关键靶器官，缺乏可靠的体外培养模型严重限制了药物发现。虽然诱导多能干细胞（iPSC）的发展彻底改变了生物医学领域的策略，但肾脏的复杂性对该技术在肾脏再生中的应用提出了额外的挑战。尽管如此，最近我们对肾脏祖细胞的发育起源及其相互诱导和自组织机制的理解取得了进展，促进了肾脏再生的研究。此后的研究表明，来源于iPSC的肾脏类器官可以作为药物发现和毒性筛选以及疾病建模的有用模型，特别是与基因编辑技术相结合。此外，在动物体内植入肾类器官的尝试表明它们作为肾移植替代来源的潜力。在这篇综述中，我们总结了肾脏类器官产生的最新进展，以及仍然存在的障碍。
Despite a continuing increase in the number of patients suffering from chronic kidney disease, currently available treatments for these patients, such as dialysis and kidney transplantation, are imperfect. The kidney is also a critical target organ vulnerable to the toxicity of various new drugs, and the lack of a reliable in vitro culture model imposes a severe limitation on drug discovery. Although the development of induced pluripotent stem cells (iPSCs) revolutionized strategies in biomedical fields, the complexity of the kidney imposed additional challenge to the application of this technology in kidney regeneration. Nonetheless, the recent advancement in our understanding on the developmental origin of kidney progenitor cells and the mechanisms of their reciprocal induction and self-organization has boosted research in kidney regeneration. Research since then has demonstrated that kidney organoids derived from iPSCs can serve as a useful model for drug discovery and toxicity screening, as well as for disease modeling, especially in combination with gene editing techniques. Moreover, attempts at kidney organoid implantation in animals have suggested their potential as an alternative source of kidney transplantation. In this review, we summarize recent progress on the generation of kidney organoids, as well as the obstacles that remain.