Stead Family Department of Pediatrics, USA.
Department of Internal Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
J Cyst Fibros. 2024 Jan;23(1):169-171. doi: 10.1016/j.jcf.2023.08.003. Epub 2023 Aug 24.
Pancreatic secretions become viscous and acidic in Cystic fibrosis (CF), highlighting the role of CFTR in pancreatic fluid and bicarbonate secretion. Forskolin-induced swelling (FIS) assay developed in intestinal organoids measures residual CFTR function. It is not known whether FIS reflects bicarbonate secretion in pancreas, an organ that secretes near-isotonic NaHCO levels. To investigate this, we generated pancreatic duct organoids from CF and non-CF pigs. Epithelial and ductal origin was confirmed with epithelial markers, ion transporters and lack of acinar, islet cell markers. CF organoids were small with no identifiable lumen; CFTR was expressed only in non-CF organoids. Utilizing FIS, organoid size increased only in response to chloride, not bicarbonate. This report highlights pancreatic duct organoids isolated for the first time from CF pigs and evidence for chloride and not bicarbonate driving pancreatic organoid swelling. These organoids would be useful to test chloride permeability of CFTR mutations that cause CF pancreatic disease.
囊性纤维化（CF）中胰腺分泌物变得粘稠且呈酸性，这突出了 CFTR 在胰腺液和碳酸氢盐分泌中的作用。在肠类器官中开发的福司可林诱导肿胀（FIS）测定法可衡量残余 CFTR 功能。尚不清楚 FIS 是否反映了分泌近等渗 NaHCO 水平的胰腺中的碳酸氢盐分泌。为了研究这一点，我们从 CF 和非 CF 猪中生成了胰腺导管类器官。上皮和导管起源通过上皮标志物、离子转运体以及缺乏腺泡和胰岛细胞标志物得到确认。CF 类器官较小，没有可识别的腔；仅在非 CF 类器官中表达 CFTR。利用 FIS，只有在响应氯离子而非碳酸氢盐时，类器官的大小才会增加。本报告首次强调了从 CF 猪中分离的胰腺导管类器官，并证明氯离子而不是碳酸氢盐驱动胰腺类器官肿胀。这些类器官将有助于测试导致 CF 胰腺疾病的 CFTR 突变的氯离子通透性。
