Generation of Humanized Liver Mouse Model by Transplant of Patient-Derived Fresh Human Hepatocytes
| Autor: | Jung Hun Lee, Myoung-Gyun Kim, S.-Y. Joo, Hyungdong Lee, S.J. Lee, Kyo Won Lee, S. K. Lee, S.J. Kim, Jae Berm Park, Byung-Ok Choi |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Ganciclovir
Time Factors medicine.medical_treatment Intraperitoneal injection Mice Transgenic Serum Albumin Human Mice SCID Biology Thymidine Kinase Immunocompromised Host Mice Immune system Species Specificity Mice Inbred NOD medicine Animals Humans Simplexvirus Serum Albumin Cell Proliferation Immunodeficient Mouse Transplantation Chimera Transplantation Keratin-18 Keratin-8 Liver regeneration Liver Regeneration Liver Transplantation Liver Thymidine kinase Models Animal Immunology Humanized mouse Hepatocytes Surgery Biomarkers Drug metabolism medicine.drug |
| Zdroj: | Transplantation Proceedings. 46:1186-1190 |
| ISSN: | 0041-1345 |
| Popis: | Some research groups have produced immunodeficient mice with human liver tissue as a model system for the analysis of drug metabolism and liver regeneration. Mouse models are important for research and development of drugs and vaccines for viral infections. Recent progress in developing humanized mouse models permits studies of adaptive immune responses, innate host responses, and therapeutic approaches for several liver diseases of viral etiology. In this study, we generated a humanized liver mouse model by transplant with fresh patient-derived hepatocytes (1 × 106 cells/mouse, intrasplenic injection) into preconditioned (50 mg/kg ganciclovir, intraperitoneal injection) mice (herpes simplex virus type 1 thymidine kinase [TK] transgene expressed within the liver of a highly immunodeficient mouse strain [NOG]). Successful reconstitution of human hepatocytes in TK-NOG mouse liver tissues was observed with a strong proliferation of human cells in a time-dependent manner, using cytokeratin 8/18 stain. Similarly, we detected significantly increased human albumin levels in TK-NOG mouse liver tissue and blood sera on immune staining and enzyme-linked immunosorbent assay. Therefore, this humanized liver mouse model provides a biomedical tool for studying human liver physiology, drug metabolism, and liver pathogenesis of viral etiology or liver regeneration. |
| Databáze: | OpenAIRE |
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