Towards Bioengineered Liver Stem Cell Transplantation Studies in a Preclinical Dog Model for Inherited Copper Toxicosis
Wilson Disease is a rare autosomal recessive liver disorder in humans. Although its clinical presentation and age of onset are highly variable, hallmarks include signs of liver disease, neurological features and so-called Kayser-Fleischer rings in the eyes of the patient. Hepatic copper accumulation...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-09-01
|
| Series: | Bioengineering |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2306-5354/6/4/88 |
| _version_ | 1797726157091635200 |
|---|---|
| author | Hedwig S. Kruitwagen Hille Fieten Louis C. Penning |
| author_facet | Hedwig S. Kruitwagen Hille Fieten Louis C. Penning |
| author_sort | Hedwig S. Kruitwagen |
| collection | DOAJ |
| description | Wilson Disease is a rare autosomal recessive liver disorder in humans. Although its clinical presentation and age of onset are highly variable, hallmarks include signs of liver disease, neurological features and so-called Kayser-Fleischer rings in the eyes of the patient. Hepatic copper accumulation leads to liver disease and eventually to liver cirrhosis. Treatment options include life-long copper chelation therapy and/or decrease in copper intake. Eventually liver transplantations are indicated. Although clinical outcome of liver transplantations is favorable, the lack of suitable donor livers hampers large numbers of transplantations. As an alternative, cell therapies with hepatocytes or liver stem cells are currently under investigation. Stem cell biology in relation to pets is in its infancy. Due to the specific population structure of dogs, canine copper toxicosis is frequently encountered in various dog breeds. Since the histology and clinical presentation resemble Wilson Disease, we combined genetics, gene-editing, and matrices-based stem cell cultures to develop a translational preclinical transplantation model for inherited copper toxicosis in dogs. Here we describe the roadmap followed, starting from the discovery of a causative copper toxicosis mutation in a specific dog breed and culminating in transplantation of genetically-engineered autologous liver stem cells. |
| first_indexed | 2024-03-12T10:41:43Z |
| format | Article |
| id | doaj.art-71a073111be542428387ceec410fb1aa |
| institution | Directory Open Access Journal |
| issn | 2306-5354 |
| language | English |
| last_indexed | 2024-03-12T10:41:43Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Bioengineering |
| spelling | doaj.art-71a073111be542428387ceec410fb1aa2023-09-02T08:06:55ZengMDPI AGBioengineering2306-53542019-09-01648810.3390/bioengineering6040088bioengineering6040088Towards Bioengineered Liver Stem Cell Transplantation Studies in a Preclinical Dog Model for Inherited Copper ToxicosisHedwig S. Kruitwagen0Hille Fieten1Louis C. Penning2Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584CM Utrecht, The NetherlandsDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584CM Utrecht, The NetherlandsDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584CM Utrecht, The NetherlandsWilson Disease is a rare autosomal recessive liver disorder in humans. Although its clinical presentation and age of onset are highly variable, hallmarks include signs of liver disease, neurological features and so-called Kayser-Fleischer rings in the eyes of the patient. Hepatic copper accumulation leads to liver disease and eventually to liver cirrhosis. Treatment options include life-long copper chelation therapy and/or decrease in copper intake. Eventually liver transplantations are indicated. Although clinical outcome of liver transplantations is favorable, the lack of suitable donor livers hampers large numbers of transplantations. As an alternative, cell therapies with hepatocytes or liver stem cells are currently under investigation. Stem cell biology in relation to pets is in its infancy. Due to the specific population structure of dogs, canine copper toxicosis is frequently encountered in various dog breeds. Since the histology and clinical presentation resemble Wilson Disease, we combined genetics, gene-editing, and matrices-based stem cell cultures to develop a translational preclinical transplantation model for inherited copper toxicosis in dogs. Here we describe the roadmap followed, starting from the discovery of a causative copper toxicosis mutation in a specific dog breed and culminating in transplantation of genetically-engineered autologous liver stem cells.https://www.mdpi.com/2306-5354/6/4/88copper toxicosisstem cell transplantationwilson diseasepreclinical large animal model |
| spellingShingle | Hedwig S. Kruitwagen Hille Fieten Louis C. Penning Towards Bioengineered Liver Stem Cell Transplantation Studies in a Preclinical Dog Model for Inherited Copper Toxicosis Bioengineering copper toxicosis stem cell transplantation wilson disease preclinical large animal model |
| title | Towards Bioengineered Liver Stem Cell Transplantation Studies in a Preclinical Dog Model for Inherited Copper Toxicosis |
| title_full | Towards Bioengineered Liver Stem Cell Transplantation Studies in a Preclinical Dog Model for Inherited Copper Toxicosis |
| title_fullStr | Towards Bioengineered Liver Stem Cell Transplantation Studies in a Preclinical Dog Model for Inherited Copper Toxicosis |
| title_full_unstemmed | Towards Bioengineered Liver Stem Cell Transplantation Studies in a Preclinical Dog Model for Inherited Copper Toxicosis |
| title_short | Towards Bioengineered Liver Stem Cell Transplantation Studies in a Preclinical Dog Model for Inherited Copper Toxicosis |
| title_sort | towards bioengineered liver stem cell transplantation studies in a preclinical dog model for inherited copper toxicosis |
| topic | copper toxicosis stem cell transplantation wilson disease preclinical large animal model |
| url | https://www.mdpi.com/2306-5354/6/4/88 |
| work_keys_str_mv | AT hedwigskruitwagen towardsbioengineeredliverstemcelltransplantationstudiesinapreclinicaldogmodelforinheritedcoppertoxicosis AT hillefieten towardsbioengineeredliverstemcelltransplantationstudiesinapreclinicaldogmodelforinheritedcoppertoxicosis AT louiscpenning towardsbioengineeredliverstemcelltransplantationstudiesinapreclinicaldogmodelforinheritedcoppertoxicosis |