Direct orthotopic implantation of hepatic organoids
| Autor: | Vivian X. Zhou, Tammy T. Chang, Macarena Lolas |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Homologous
0301 basic medicine Male medicine.medical_treatment Chronic Liver Disease and Cirrhosis Clinical Sciences Liver transplantation Biology Inbred C57BL Oral and gastrointestinal Article 03 medical and health sciences Liver disease Mice 0302 clinical medicine Organ Culture Techniques Tissue engineering Organoid medicine Animals Hepatectomy Transplantation Homologous Transplantation 5.2 Cellular and gene therapies Tissue Engineering Liver Disease medicine.disease Three-dimensional culture Liver Transplantation Mice Inbred C57BL Organoids Good Health and Well Being 030104 developmental biology medicine.anatomical_structure Hepatocyte Immunology Cancer research Hepatic stellate cell 030211 gastroenterology & hepatology Surgery Female Development of treatments and therapeutic interventions Digestive Diseases Biotechnology Liver organoids |
| Zdroj: | Zhou, VX; Lolas, M; & Chang, TT. (2017). Direct orthotopic implantation of hepatic organoids. JOURNAL OF SURGICAL RESEARCH, 211, 251-260. doi: 10.1016/j.jss.2016.12.028. UC San Francisco: Retrieved from: http://www.escholarship.org/uc/item/6kp0g96r |
| ISSN: | 1095-8673 |
| Popis: | Background Liver organoids show potential for development as a tissue replacement therapy for patients with end-stage liver disease, but efficient methods for introducing organoids into host livers have not been established. In this study, we aimed to develop a surgical technique to implant hepatic organoids into the liver and assess their engraftment. Methods Donor hepatocytes were isolated from ROSA26 C57BL/6 mice, so that engrafted cells, when implanted into wild-type mice, could be easily identified by X-gal staining. Hepatic organoids were generated by three-dimensional culture in rotating wall vessel bioreactors. We qualitatively and quantitatively compared organoid engraftment to that of single-cell hepatocyte transplants. In addition, we determined the effect of adding stellate cells to hepatocytes to form co-aggregated organoids and the effect of partial hepatectomy of the host liver on organoid engraftment. Results Direct orthotopic implantation of hepatic organoids within a hepatotomy site resulted in local engraftment of exogenous hepatocytes with limited durability. Hepatocyte-stellate cell organoids produced more extracellular matrix but did not significantly improve engraftment compared with hepatocyte-alone organoids. Partial hepatectomy of the host liver led to significantly decreased engraftment of organoids. Survival of organoids was limited by the presence of apoptotic hepatocytes within organoids as early as 1 h after implantation. Organoids eventually became necrotic and elicited a chronic inflammatory giant cell reaction similar to a foreign body response. Conclusions With additional organoid and host factor optimization, direct orthotopic implantation of hepatic organoids may be an approach to introduce large numbers of exogenous hepatocytes into recipient livers. |
| Databáze: | OpenAIRE |
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