小肾细胞器遗传疾病模型

“The study provides a proof-of-concept that we can use a genetic approach to make kidney disease in a dish,” said Joseph Bonventre, MD, PhD, HSCI Principal Faculty, Chief of the Renal Division at Brigham and Women’s Hospital at Harvard and the study’s senior author. “We were interested in creating disease models using these kidney organoids," he added。

Just last week, Bonventre and a team of HSCI/BWH investigators published research involving the creation of human kidney organoids, three-dimensional mini-organs grown in a lab dish, to model human kidney development and to test for drug toxicity. Now, using gene-editing tools, researchers can engineer these mini-kidneys with specific genetic diseases。

Using CRISPR technology, Bonventre and colleagues introduced into healthy human pluripotent stem cells either the gene mutations associated with polycystic kidney disease or those associated with glomerulonephritis。

The scientists then coaxed the stem cells to differentiate into mature kidney cells that self-assembled into functional organoids with the physical complications related to their genetic mutations; for example, organoids with polycystic kidney disease formed cysts, while organoids with changes in a protein that is implicated in glomerulonephritis displayed altered cell to cell interactions, which could ultimately lead to leaky filters in the mature kidney。

“Mutation of a single gene results in changes in kidney structures associated with human disease, allowing better understanding of the disease and serving as models to develop therapeutic agents to treat these diseases,” Bonventre said。

Kidney disease costs the United States 40 billion dollars per year and affects 700 million people worldwide. Twelve million patients have polycystic kidney disease and two million people have complete kidney failure. Dialysis and kidney transplantation, the only options for kidney failure patients, can cause harmful side effects and poor quality-of-life。

“这些转基因迷你肾脏已经告诉我们，人类的疾病归结为简单的组件，可以在培养皿中创造出来的，” 这项研究的第一作者，本杰明Freedman博士，曾与塞萨尔鲍文垂BWH已经为在大学的助理教授职位 华盛顿。“这为我们提供了更快、更好的方法来检测可能在人类工作的药物和治疗方法。”

源哈佛干细胞研究所；由汉娜L.罗宾斯写，HSCI传讯经理

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