Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis
Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis
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DOI：
10.1016/j.celrep.2019.01.068
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发表时间：
2019-02-12
期刊：
影响因子：
8.8
通讯作者：
van der Ent, Cornelis K.
中科院分区：
文献类型：
--
作者：
Berkers, Gitte;van Mourik, Peter;van der Ent, Cornelis K.
使用患者来源的干细胞培养进行的体外药物测试提供了单独选择有效治疗方法的机会。在这里，我们提供了一项研究，证明囊性纤维化(CF)患者直肠器官的体外药物反应与体内两个治疗终点的变化相关。我们使用基于Forsklin诱导的肿胀的直肠衍生有机化合物的功能测试来测量个体的体外有效性，并研究其与体内效应的相关性。体外器官反应与肺反应的变化和汗液氯化物浓度的变化有关。受试者的工作特性曲线表明，以有机物为基础的测试定义临床反应的准确性很好到很好。这项研究表明，使用干细胞培养的体外试验可以前瞻性地为患者选择有效的治疗方法，并表明生物库干细胞资源可以用于以经济高效和对患者友好的方式定制个性化的治疗方法。
In vitro drug tests using patient-derived stem cell cultures offer opportunities to individually select efficacious treatments. Here, we provide a study that demonstrates that in vitro drug responses in rectal organoids from individual patients with cystic fibrosis (CF) correlate with changes in two in vivo therapeutic endpoints. We measured individual in vitro efficaciousness using a functional assay in rectum-derived organoids based on forskolin-induced swelling and studied the correlation with in vivo effects. The in vitro organoid responses correlated with both change in pulmonary response and change in sweat chloride concentration. Receiver operating characteristic curves indicated good-to-excellent accuracy of the organoid-based test for defining clinical responses. This study indicates that an in vitro assay using stem cell cultures can prospectively select efficacious treatments for patients and suggests that biobanked stem cell resources can be used to tailor individual treatments in a cost-effective and patient-friendly manner.