PT -期刊文章AU -塞特，乔瓦尼AU -洛西塞罗，斯特凡尼亚AU - Blaconà，乔瓦娜AU -皮埃安德烈，西尔维娅AU -布鲁诺，萨宾娜玛丽亚AU -萨尔瓦蒂，瓦伦蒂娜AU -卡斯特利，日耳曼AU -法尔奇，马里奥AU -法布里齐，贝内德塔AU -西米诺，朱塞佩AU -德玛丽亚，鲁杰罗AU -比弗尼，毛罗AU -埃拉莫，阿德瑞娜AU -卢卡雷利，马可TI - Theratyping囊胞性纤维症体外< em > < / em >在ALI-culture和瀑样模型产生patient-derived鼻上皮有条件地重组干细胞援助- 10.1183/13993003.00908 -2021 DP - 2021年1月01 TA -欧洲呼吸杂志PG - 2100908 4099 - //www.qdcxjkg.com/content/early/2021/07/29/13993003.00908 - 2021. -短4100 - //www.qdcxjkg.com/content/early/2021/07/29/13993003.00908 - 2021. -完整的AB -囊性纤维化(CF)的问题是由于致病variants in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Recent improvement enabled pharmacologic therapy aiming at restoring mutated CFTR expression and function. CFTR “modulators” have revolutionised the CF therapeutic landscape, particularly the last approved Trikafta. This drug-combination is indicated by FDA and very recently by EMA for genotypes carrying at least one copy of CFTR with F508del pathogenic variant. However, several genotypes, are not eligible for Trikafta treatment, yet.Materials/patients and methods We exploited an innovative cellular approach allowing highly efficient in vitro-expansion of airway epithelial stem cells (AESC) through conditional reprogramming (CRC) from nasal brushing of CF patients. This approach, coupled to development of AESC-derived personalised disease models, as organoids and air liquid interface (ALI) cultures, revealed highly suitable for CFTR pharmacological-testing.Results and answer to the question We fully validated the experimental models and implemented the CFTR functional assays and biochemical CFTR protein characterisation, that allowed to evaluate the efficacy of clinically available modulators in restoring CFTR maturation and function of each patient-derived “avatar” (theratyping). F508del homozygous genotypes, used as controls, confirmed the higher clinical activity of Trikafta in comparison with older modulators. 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 Blaconà 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.