Induction of steady-state glomeruloid sphere by self-assembly from human embryonic kidney cells
Induction of steady-state glomeruloid sphere by self-assembly from human embryonic kidney cells
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通过人胚胎肾细胞自组装诱导稳态肾小球球
DOI：
10.1016/j.bbrc.2018.11.160
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发表时间：
2019
影响因子：
3.1
通讯作者：
Ochi Arisa
中科院分区：
文献类型：
--
作者：
Abe Hideharu;Sakurai Akiko;Ochi Arisa
肾小球是一种称为簇状毛细血管的网络，位于肾脏中肾单位的起点。在这里，我们描述了一种新的方法来诱导一个宏观上可见的三维球状肾小球(GLS)。此过程不需要任何额外的细胞因子，在24 h内完成球体的形成。形成完成后，GLS保持稳定状态至少5天，没有增殖，活性也没有下降。因此，此程序可在较长时间内辅助各种化验。总体而言，我们的方案允许非常简单地混合来自不同来源的细胞，以获得细粒度和高度分散的GLSS。肾滤过屏障是一种独特的结构，以足细胞和内皮细胞的复杂三维结构为特征。GLS表现出与成人肾脏相似的许多足细胞特异性基因谱的诱导，表明球体的形成过程对足细胞的成熟是重要的。局灶节段性肾小球硬化(FSGS)是激素抵抗型肾病综合征的主要病因之一，患者血清FSGS中的某些循环通透性因子参与了该病的发病机制。FSGS患者血清诱导GLS塌陷，类似于患者肾小球硬化的表现。总之，GLS的研究和使用可能为阐明成人肾脏类似情况下肾小球复杂和不明原因事件的分子机制提供一种新的方法。
The glomerulus is a network of capillaries known as a tuft, located at the beginning of a nephron in the kidney. Here we describe a novel method for the induction of a macroscopically visible three-dimensional glomerulus-like sphere (GLS). This procedure did not require any additional cytokines and completed the formation of spheres within 24 h. After the formation was complete, GLS maintained a steady state for at least five days without proliferation and without a decrease in viability. Therefore, this procedure assists various assays for a prolong period of time. Overall, our protocol allows for a very simple mixing of cells from different sources to obtain fine-grained and highly dispersed GLSs. The kidney filtration barrier is a unique structure characterized by a complex three-dimensional framework of podocytes and endothelial cells. GLS exhibited the induction of many podocyte-specific gene profiles similar to those in adult human kidneys, suggesting that the sphere formation process is important for the maturation of podocytes. Focal segmental glomerulosclerosis (FSGS) is one of the major causes of steroid-resistant nephrotic syndrome, and some circulating permeability factors in the patient's serum FSGS have been implicated in the pathogenesis of the disease. Serum from patients with FSGS induced the collapse of GLS, which imitates the appearance of glomerulosclerosis in patients. In conclusion, the investigation and use of GLS may provide a novel method to elucidate the molecular mechanisms underlying complicated and unexplained events in glomeruli in a similar condition in adult kidneys.