Towards Bioengineered Liver Stem Cell Transplantation Studies in a Preclinical Dog Model for Inherited Copper Toxicosis
| Autor: | Louis C. Penning, Hille Fieten, Hedwig S. Kruitwagen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Pathology
medicine.medical_specialty Cirrhosis 040301 veterinary sciences Wilson Disease Liver Stem Cell Bioengineering Disease Review lcsh:Technology stem cell transplantation preclinical large animal model Liver disorder 0403 veterinary science 03 medical and health sciences Liver disease medicine lcsh:QH301-705.5 030304 developmental biology 0303 health sciences lcsh:T business.industry 04 agricultural and veterinary sciences medicine.disease Transplantation lcsh:Biology (General) copper toxicosis Age of onset Stem cell business |
| Zdroj: | Bioengineering Bioengineering, Vol 6, Iss 4, p 88 (2019) |
| ISSN: | 2306-5354 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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