Basic Medical Sciences Department, College of Medicine, Qatar University, Doha, Qatar.
Diabetes Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Education City, Qatar Foundation, Doha, Qatar.
PLoS One. 2022 Aug 9;17(8):e0272091. doi: 10.1371/journal.pone.0272091. eCollection 2022.
Cystic fibrosis (CF) is a hereditary autosomal recessive disorder caused by a range of mutations in the CF Transmembrane Conductance Regulator (CFTR) gene. This gene encodes the CFTR protein, which acts as a chloride channel activated by cyclic AMP (cAMP). This meta-analysis aimed to compare the responsiveness of induced pluripotent stem cells (iPSCs) to cAMP analogues to that of commonly used animal models.
Databases searched included PubMed, Scopus, and Medline from inception to January 2020. A total of 8 and 3 studies, respectively, for animal models and iPSCs, were analyzed. Studies were extracted for investigating cAMP-stimulated anion transport by measuring the short circuit current (Isc) of chloride channels in different animal models and iPSC systems We utilized an inverse variance heterogeneity model for synthesis.
Our analysis showed considerable heterogeneity in the mean Isc value in both animal models and iPSCs studies (compared to their WT counterparts), and both suffer from variable responsiveness based on the nature of the underlying model. There was no clear advantage of one over the other.
Studies on both animal and iPSCs models generated considerable heterogeneity. Given the potential of iPSC-derived models to study different diseases, we recommend paying more attention to developing reproducible models of iPSC as it has potential if adequately developed.
囊性纤维化（CF）是一种常染色体隐性遗传疾病，由 CF 跨膜电导调节因子（CFTR）基因的一系列突变引起。该基因编码 CFTR 蛋白，作为一种受环磷酸腺苷（cAMP）激活的氯离子通道。本荟萃分析旨在比较诱导多能干细胞（iPSC）对 cAMP 类似物的反应与常用动物模型的反应。
检索的数据库包括 PubMed、Scopus 和 Medline，从开始到 2020 年 1 月。分别对动物模型和 iPSC 进行了 8 项和 3 项研究的分析。这些研究分别提取出来，用于研究不同动物模型和 iPSC 系统中 cAMP 刺激的阴离子转运，通过测量氯离子通道的短路电流（Isc）。我们利用逆方差异质性模型进行综合。
我们的分析表明，在动物模型和 iPSC 研究中（与 WT 相比），平均 Isc 值存在相当大的异质性，并且两者都根据潜在模型的性质而存在可变的反应性。一种模型并不比另一种模型具有明显的优势。
动物和 iPSC 模型的研究都产生了相当大的异质性。鉴于 iPSC 衍生模型在研究不同疾病方面的潜力，如果得到充分开发，我们建议更多地关注开发可重复的 iPSC 模型，因为它具有潜力。
