Testing organ-specific responses to therapies in tissues differentiated from Cystic Fibrosis patient derived iPSCs
Cystic Fibrosis (CF) is a life-shortening disease that is caused by mutations in the CFTR gene, a gene that is expressed in multiple organs. There are several primary tissue models of CF disease, including nasal epithelial cultures and rectal organoids, that are effective in reporting the potential...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Stem Cell Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1873506125000030 |
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| author | Abdelkader Daoud Sunny Xia Onofrio Laselva Janet Jiang Christine E. Bear |
| author_facet | Abdelkader Daoud Sunny Xia Onofrio Laselva Janet Jiang Christine E. Bear |
| author_sort | Abdelkader Daoud |
| collection | DOAJ |
| description | Cystic Fibrosis (CF) is a life-shortening disease that is caused by mutations in the CFTR gene, a gene that is expressed in multiple organs. There are several primary tissue models of CF disease, including nasal epithelial cultures and rectal organoids, that are effective in reporting the potential efficacy of mutation-targeted therapies called CFTR modulators. However, there is the well-documented variation in tissue dependent, therapeutic response amongst CF patients, even those with the same CF-causing mutation. Hence, there is an interest in developing strategies for comparing therapeutic efficacy in different organs relative to isogenic controls. In this study, we evaluated the CFTR chloride channel response to the highly effective CFTR modulator: Trikafta, in CF patient specific, iPSC-derived colonic and airway cultures relative to mutation-corrected (non-CF) tissues from that same individual. We measured pharmacological rescue in both tissues. This proof-of-concept study provides a roadmap for future comparisons of patient-specific CF therapeutic responses in both pulmonary and extra-pulmonary systems. |
| format | Article |
| id | doaj-art-2ee8b19e2f834cd5b68f8974c8a15f06 |
| institution | DOAJ |
| issn | 1873-5061 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Research |
| spelling | doaj-art-2ee8b19e2f834cd5b68f8974c8a15f062025-08-20T02:43:20ZengElsevierStem Cell Research1873-50612025-03-018310365310.1016/j.scr.2025.103653Testing organ-specific responses to therapies in tissues differentiated from Cystic Fibrosis patient derived iPSCsAbdelkader Daoud0Sunny Xia1Onofrio Laselva2Janet Jiang3Christine E. Bear4Programme in Molecular Medicine, Research Institute for SickKids Hospital, Toronto, CanadaProgramme in Molecular Medicine, Research Institute for SickKids Hospital, Toronto, Canada; Department of Physiology, University of Toronto, ON, CanadaProgramme in Molecular Medicine, Research Institute for SickKids Hospital, Toronto, Canada; Department of Clinical and Experimental Medicine, University of Foggia, ItalyProgramme in Molecular Medicine, Research Institute for SickKids Hospital, Toronto, CanadaProgramme in Molecular Medicine, Research Institute for SickKids Hospital, Toronto, Canada; Department of Clinical and Experimental Medicine, University of Foggia, Italy; Corresponding author.Cystic Fibrosis (CF) is a life-shortening disease that is caused by mutations in the CFTR gene, a gene that is expressed in multiple organs. There are several primary tissue models of CF disease, including nasal epithelial cultures and rectal organoids, that are effective in reporting the potential efficacy of mutation-targeted therapies called CFTR modulators. However, there is the well-documented variation in tissue dependent, therapeutic response amongst CF patients, even those with the same CF-causing mutation. Hence, there is an interest in developing strategies for comparing therapeutic efficacy in different organs relative to isogenic controls. In this study, we evaluated the CFTR chloride channel response to the highly effective CFTR modulator: Trikafta, in CF patient specific, iPSC-derived colonic and airway cultures relative to mutation-corrected (non-CF) tissues from that same individual. We measured pharmacological rescue in both tissues. This proof-of-concept study provides a roadmap for future comparisons of patient-specific CF therapeutic responses in both pulmonary and extra-pulmonary systems.http://www.sciencedirect.com/science/article/pii/S1873506125000030Cystic fibrosisiPSC-derived colonic organoidsTRIKAFTA |
| spellingShingle | Abdelkader Daoud Sunny Xia Onofrio Laselva Janet Jiang Christine E. Bear Testing organ-specific responses to therapies in tissues differentiated from Cystic Fibrosis patient derived iPSCs Stem Cell Research Cystic fibrosis iPSC-derived colonic organoids TRIKAFTA |
| title | Testing organ-specific responses to therapies in tissues differentiated from Cystic Fibrosis patient derived iPSCs |
| title_full | Testing organ-specific responses to therapies in tissues differentiated from Cystic Fibrosis patient derived iPSCs |
| title_fullStr | Testing organ-specific responses to therapies in tissues differentiated from Cystic Fibrosis patient derived iPSCs |
| title_full_unstemmed | Testing organ-specific responses to therapies in tissues differentiated from Cystic Fibrosis patient derived iPSCs |
| title_short | Testing organ-specific responses to therapies in tissues differentiated from Cystic Fibrosis patient derived iPSCs |
| title_sort | testing organ specific responses to therapies in tissues differentiated from cystic fibrosis patient derived ipscs |
| topic | Cystic fibrosis iPSC-derived colonic organoids TRIKAFTA |
| url | http://www.sciencedirect.com/science/article/pii/S1873506125000030 |
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