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Bartholomeus T van den Berge^1,2, Martijn van den Broek^2,3, Gianluca Di Giovanni¹

¹Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboudumc, Nijmegen, The Netherlands.

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概括

这项研究开发了一种针对焦点细分性淋巴结核硬化症 (FSGS) 复发的个性化模型,使用诱导的多能干细胞衍生的细胞. 捐赠体细胞对循环因子的敏感性可能预测移植后FSGS复发.

科学领域:

腎臟病學 (nephrology) 是一種醫學專業.
干细胞生物学干细胞生物学
遗传学是一个遗传学.

背景情况:

主要的焦点细分质硬化 (FSGS) 涉及细胞损伤和耐治疗性性综合征.
接受脏移植的人面临10-50%的FSGS复发风险 (rFSGS),可能是由于循环透性因子 (CPF).
捐赠体细胞对CPF的敏感性是rFSGS病变发生的一个潜在的,但尚未被探索的因素.

研究的目的:

开发一个个性化的体外模型来评估FSGS和rFSGS.
调查捐赠体受体对rFSGS中循环因子敏感性的作用.
评估诱导多能干细胞 (iPSC) 衍生的 podocytes 在建模患者特异性疾病反应中的实用性.

主要方法:

从五个个体 (有三个rFSGS,两个没有) 产生了患者和脏捐赠者衍生的iPSC podocytes.
从相应患者的血/血清中暴露iPSC衍生型细胞,以评估细胞损伤.
使用F-actin再分配 (FAR) 测定,以及ROS形成和颗粒度,以量化 podocyte 损伤.

主要成果:

F-actin再分配 (FAR) 试验有效地区分了患者和健康的捐赠体受体细胞反应.
患者的血诱导了相应患者的iPSC-podocytes中显著的FAR (除了NPHS2突变的一例).
暴露于rFSGS患者血的捐赠者iPSC-podocytes显示出显著的FAR,与暴露于无rFSGS患者血的患者不同.

结论:

使用iPSC衍生的供体细胞的体外测定显示出个性化rFSGS风险评估的前景.
这种个性化的模型可以帮助预测移植后FSGS复发的可能性.
需要更大的队列研究来验证这些初步发现的临床应用.

关键词:

循环透性因子的循环透性因子葡萄细胞 (podocytes) 是一个细胞.蛋白质尿症是一种蛋白质尿症.复发性焦点细分性淋巴结核硬化 (FSGS)移植移植移植移植

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