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A Hepatocellular Cancer Patient-derived Organoid Xenograft Model to Investigate Impact of Liver Regeneration on Tumor Growth.
Haak, Fabian; Hess, Gabriel Fridolin; Sedlaczek, Philipp; Soysal, Savas Deniz; Vosbeck, Jürg; Piscuoglio, Salvatore; Coto-Llerena, Mairene; Kollmar, Otto.
Afiliación
  • Haak F; Clarunis, Department of Visceral Surgery, University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital Basel.
  • Hess GF; Clarunis, Department of Visceral Surgery, University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital Basel.
  • Sedlaczek P; Clarunis, Department of Visceral Surgery, University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital Basel.
  • Soysal SD; Faculty of Medicine, University of Basel.
  • Vosbeck J; Institute of Medical Genetics and Pathology, University Hospital Basel.
  • Piscuoglio S; Visceral Surgery and Precision Medicine Research Laboratory, Department of Biomedicine, University of Basel; IRCCS Humanitas Research Hospital.
  • Coto-Llerena M; Visceral Surgery and Precision Medicine Research Laboratory, Department of Biomedicine, University of Basel.
  • Kollmar O; Clarunis, Department of Visceral Surgery, University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital Basel; otto.kollmar@clarunis.ch.
J Vis Exp ; (204)2024 Feb 02.
Article en En | MEDLINE | ID: mdl-38372340
ABSTRACT
Recurrence poses a notable challenge after hepatocellular carcinoma (HCC) treatment, impacting more than 70% of patients who undergo surgical resection. Recurrence stems from undetected micro-metastasis or de novo cancer, potentially triggered by postsurgical liver regeneration. Prior research employed HCC cell lines in orthotopic models to study the impact of liver regeneration, but their limited validity prompted the need for a more representative model. Here, we introduce a novel approach utilizing patient-derived HCC organoids to investigate the influence of liver regeneration on HCC. Patient tumor tissues are processed to create tumor organoids, embedded in a three-dimensional basement membrane matrix, and cultured in a liver-specific medium. One million organoids are injected into the right superior lobe (RSL) of immunodeficient mice, confirming macroscopic tumor growth through sonography. The intervention group undergoes resection of the left lateral lobe (LLL) (30% of total liver volume) or additionally, the middle lobe (ML) (65% of total liver volume) to induce liver regeneration within the tumor site. The control group experiences re-laparotomy without liver tissue resection. After 2 weeks, both groups undergo tumor and normal tissue explantation. In conclusion, this patient-derived HCC organoid model offers a robust platform to investigate the impact of liver regeneration post-cancer resection. Its multi-cellular composition, genetic diversity, and prolonged culture capabilities make it an invaluable tool for studying HCC recurrence mechanisms and potential interventions.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Límite: Animals / Humans Idioma: En Revista: J Vis Exp Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Límite: Animals / Humans Idioma: En Revista: J Vis Exp Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos