Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids
The recent development of 3D-liver stem cell cultures (hepatic organoids) opens up new avenues for gene and/or stem cell therapy to treat liver disease. To test safety and efficacy, a relevant large animal model is essential but not yet established. Because of its shared pathologies and disease path...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-11-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671115002647 |
| _version_ | 1818299847591067648 |
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| author | Sathidpak Nantasanti Bart Spee Hedwig S. Kruitwagen Chen Chen Niels Geijsen Loes A. Oosterhoff Monique E. van Wolferen Nicolas Pelaez Hille Fieten Richard W. Wubbolts Guy C. Grinwis Jefferson Chan Meritxell Huch Robert R.G. Vries Hans Clevers Alain de Bruin Jan Rothuizen Louis C. Penning Baukje A. Schotanus |
| author_facet | Sathidpak Nantasanti Bart Spee Hedwig S. Kruitwagen Chen Chen Niels Geijsen Loes A. Oosterhoff Monique E. van Wolferen Nicolas Pelaez Hille Fieten Richard W. Wubbolts Guy C. Grinwis Jefferson Chan Meritxell Huch Robert R.G. Vries Hans Clevers Alain de Bruin Jan Rothuizen Louis C. Penning Baukje A. Schotanus |
| author_sort | Sathidpak Nantasanti |
| collection | DOAJ |
| description | The recent development of 3D-liver stem cell cultures (hepatic organoids) opens up new avenues for gene and/or stem cell therapy to treat liver disease. To test safety and efficacy, a relevant large animal model is essential but not yet established. Because of its shared pathologies and disease pathways, the dog is considered the best model for human liver disease. Here we report the establishment of a long-term canine hepatic organoid culture allowing undifferentiated expansion of progenitor cells that can be differentiated toward functional hepatocytes. We show that cultures can be initiated from fresh and frozen liver tissues using Tru-Cut or fine-needle biopsies. The use of Wnt agonists proved important for canine organoid proliferation and inhibition of differentiation. Finally, we demonstrate that successful gene supplementation in hepatic organoids of COMMD1-deficient dogs restores function and can be an effective means to cure copper storage disease. |
| first_indexed | 2024-12-13T04:57:44Z |
| format | Article |
| id | doaj.art-1abf448ce02c4f37b5e21cdc6b0ded40 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-13T04:57:44Z |
| publishDate | 2015-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-1abf448ce02c4f37b5e21cdc6b0ded402022-12-21T23:58:52ZengElsevierStem Cell Reports2213-67112015-11-015589590710.1016/j.stemcr.2015.09.002Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic OrganoidsSathidpak Nantasanti0Bart Spee1Hedwig S. Kruitwagen2Chen Chen3Niels Geijsen4Loes A. Oosterhoff5Monique E. van Wolferen6Nicolas Pelaez7Hille Fieten8Richard W. Wubbolts9Guy C. Grinwis10Jefferson Chan11Meritxell Huch12Robert R.G. Vries13Hans Clevers14Alain de Bruin15Jan Rothuizen16Louis C. Penning17Baukje A. Schotanus18Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the NetherlandsDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the NetherlandsDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the NetherlandsDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the NetherlandsDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the NetherlandsDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the NetherlandsDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the NetherlandsDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the NetherlandsDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the NetherlandsCentre for Cellular Imaging (CCI), Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CL, the NetherlandsDepartment of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CL, the NetherlandsDepartment of Chemistry, University of California, Berkeley, Berkeley, CA 94720-1460, USAHubrecht Institute and University Medical Centre, Utrecht, 3584 CT, the NetherlandsHubrecht Institute and University Medical Centre, Utrecht, 3584 CT, the NetherlandsHubrecht Institute and University Medical Centre, Utrecht, 3584 CT, the NetherlandsDepartment of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CL, the NetherlandsDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the NetherlandsDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the NetherlandsDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CM, the NetherlandsThe recent development of 3D-liver stem cell cultures (hepatic organoids) opens up new avenues for gene and/or stem cell therapy to treat liver disease. To test safety and efficacy, a relevant large animal model is essential but not yet established. Because of its shared pathologies and disease pathways, the dog is considered the best model for human liver disease. Here we report the establishment of a long-term canine hepatic organoid culture allowing undifferentiated expansion of progenitor cells that can be differentiated toward functional hepatocytes. We show that cultures can be initiated from fresh and frozen liver tissues using Tru-Cut or fine-needle biopsies. The use of Wnt agonists proved important for canine organoid proliferation and inhibition of differentiation. Finally, we demonstrate that successful gene supplementation in hepatic organoids of COMMD1-deficient dogs restores function and can be an effective means to cure copper storage disease.http://www.sciencedirect.com/science/article/pii/S2213671115002647 |
| spellingShingle | Sathidpak Nantasanti Bart Spee Hedwig S. Kruitwagen Chen Chen Niels Geijsen Loes A. Oosterhoff Monique E. van Wolferen Nicolas Pelaez Hille Fieten Richard W. Wubbolts Guy C. Grinwis Jefferson Chan Meritxell Huch Robert R.G. Vries Hans Clevers Alain de Bruin Jan Rothuizen Louis C. Penning Baukje A. Schotanus Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids Stem Cell Reports |
| title | Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids |
| title_full | Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids |
| title_fullStr | Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids |
| title_full_unstemmed | Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids |
| title_short | Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids |
| title_sort | disease modeling and gene therapy of copper storage disease in canine hepatic organoids |
| url | http://www.sciencedirect.com/science/article/pii/S2213671115002647 |
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