@文章{Sette2100908，作者={塞特，乔瓦尼和罗西塞罗，斯蒂凡尼亚和布拉孔{\ ' a}，乔瓦娜和皮埃安德烈，西尔维亚和布鲁诺，萨宾娜·玛丽亚和萨尔瓦蒂，瓦伦蒂娜和卡斯特利，日耳曼娜和法尔奇，马里奥和法布里齐，贝内德塔和西米诺，朱塞佩和德玛丽亚，鲁杰罗和比弗尼，毛罗和埃拉莫，阿德里亚娜和卢卡雷利，马可}，标题={在患者来源的鼻上皮有条件重编程干细胞体外培养和类器官模型中出现的异型性囊性纤维化}，定位-id ={2100908}，年份= {2021}，doi ={10.1183/13993003.00908-2021}，发行商={欧洲呼吸学会}，摘要={问题囊性纤维化(CF)是由于囊性纤维化跨膜传导调节基因(CFTR)的致病变异。188bet官网地址最近的改进使药理学治疗能够恢复突变的CFTR表达和功能。CFTR调制器已经彻底改变了CF治疗领域，特别是最近批准的Trikafta。该药物组合被FDA和最近的EMA指定为携带至少一个CFTR拷贝的F508del致病变体的基因型。然而，一些基因型还不适合Trikafta治疗。材料/患者和方法我们利用一种创新的细胞方法，通过条件重编程(CRC)从CF患者的鼻刷中高效地体外扩增气道上皮干细胞(AESC)。这种方法，加上aesc衍生的个性化疾病模型的开发，如类器官和气液界面(ALI)培养，显示非常适合CFTR药物测试。结果和问题的答案我们充分验证了实验模型，并实现了CFTR功能测定和CFTR蛋白生化表征，这允许评估临床可用的调节剂在恢复CFTR成熟和每个患者衍生的{\textquotedblleft}化身(异型)功能方面的功效。F508del纯合基因型作为对照，证实Trikafta与旧的调节剂相比具有更高的临床活性。 Trikafta showed its efficacy also on three rare genotypes previously not eligible for modulators-treatment, opening the way to clinical translation. Finally, encouraging results for innovative drug combinations were also obtained.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Giovanni Sette has nothing to disclose.Conflict of interest: Stefania Lo Cicero has nothing to disclose.Conflict of interest: Giovanna Blacon{\`a} has nothing to disclose.CConflict of interest: Silvia Pierandrei has nothing to disclose.Conflict of interest: Sabina Maria Bruno has nothing to disclose.Conflict of interest: Valentina Salvati has nothing to disclose.Conflict of interest: Germana Castelli has nothing to disclose.Conflict of interest: Mario Falchi has nothing to disclose.Conflict of interest: Benedetta Fabrizzi has nothing to disclose.Conflict of interest: Giuseppe Cimino has nothing to disclose.Conflict of interest: Ruggero De Maria has nothing to disclose.Conflict of interest: Mauro Biffoni has nothing to disclose.Conflict of interest: Adriana Eramo has nothing to disclose.Conflict of interest: Marco Lucarelli has nothing to disclose.}, issn = {0903-1936}, URL = {//www.qdcxjkg.com/content/early/2021/07/29/13993003.00908-2021}, eprint = {//www.qdcxjkg.com/content/early/2021/07/29/13993003.00908-2021.full.pdf}, journal = {European Respiratory Journal} }