Nephrotoxicity Assessment with Human Kidney Tubuloids using Spherical Nucleic Acid-Based mRNA Nanoflares.
Nephrotoxicity Assessment with Human Kidney Tubuloids using Spherical Nucleic Acid-Based mRNA Nanoflares.
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DOI：
10.1021/acs.nanolett.1c01840
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发表时间：
2021-07-14
期刊：
影响因子：
10.8
通讯作者：
Bonventre, Joseph, V
中科院分区：
文献类型：
--
作者：
Wiraja, Christian;Mori, Yutaro;Ichimura, Takaharu;Hwang, Jangsun;Xu, Chenjie;Bonventre, Joseph, V
关键词：
药物诱导的肾毒性是急性肾损伤的重要原因，与患者发病率和死亡率相关，并且通常是在大量资源分配后终止药物开发的原因。我们已经开发了一种人肾小管样系统，其在3D培养中表型模仿肾近端小管，这是大多数肾毒物的主要损伤部位。传统的终点测定通常在已经失去其分化表型的细胞的2D培养物上进行。在此，我们将微管系统与Nanoflare（NF）mRNA纳米传感器配对，以实现药物肾毒性的简便，实时评估。使用肾损伤分子-1（KIM-1）mRNA作为模型损伤生物标志物，我们验证了NF在工程和腺病毒转染细胞中的特异性，并证实了它们报告马兜铃酸和顺铂引起的肾小管细胞损伤的功效。该系统还有助于肾毒性筛选，如10个代表性抗癌部分所示。5-氟尿嘧啶和紫杉醇诱导急性肾小管损伤，如NF信号增加所反映。
Drug-induced nephrotoxicity represents an important cause of acute kidney injury with associated patient morbidity and mortality and is often responsible for termination of drug development, after extensive resource allocation. We have developed a human kidney tubuloid system that phenocopies, in 3D culture, kidney proximal tubules, a primary injury site of most nephrotoxicants. Traditional end point assays are often performed on 2D cultures of cells that have lost their differentiated phenotype. Herein, we pair a tubuloid system with Nanoflare (NF) mRNA nanosensors to achieve a facile, real-time assessment of drug nephrotoxicity. Using kidney injury molecule-1 (KIM-1) mRNA as a model injury biomarker, we verify NF specificity in engineered and adenovirus-transfected cells and confirm their efficacy to report tubular cell injury by aristolochic acid and cisplatin. The system also facilitates nephrotoxicity screening as demonstrated with 10 representative anticancer moieties. 5-Fluorouracil and paclitaxel induce acute tubular injury, as reflected by an NF signal increase.
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DOI：
10.1186/s13054-016-1352-z
发表时间：
2016-07-04
期刊：
Critical care (London, England)
影响因子：
--
作者：
O'Neal JB;Shaw AD;Billings FT 4th
通讯作者：
Billings FT 4th
PD-1和PD-L1检查点信号传导抑制癌症免疫疗法：机制，组合和临床结果。
影响因子：
5.6
作者：
Alsaab HO;Sau S;Alzhrani R;Tatiparti K;Bhise K;Kashaw SK;Iyer AK
通讯作者：
Iyer AK
影响因子：
41.5
作者：
Ferenbach, David A.;Bonventre, Joseph V.
通讯作者：
Bonventre, Joseph V.
影响因子：
6.7
作者：
Chappell, Jill C.;Turner, P. Kellie;Bonventre, Joseph, V
通讯作者：
Bonventre, Joseph, V
DOI：
10.2147/dddt.s137783
发表时间：
2018
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Corona SP;Generali D
通讯作者：
Generali D