Your browser doesn't support javascript.
loading
Ex vivo culture of intact human patient derived pancreatic tumour tissue.
Kokkinos, John; Sharbeen, George; Haghighi, Koroush S; Ignacio, Rosa Mistica C; Kopecky, Chantal; Gonzales-Aloy, Estrella; Youkhana, Janet; Timpson, Paul; Pereira, Brooke A; Ritchie, Shona; Pandzic, Elvis; Boyer, Cyrille; Davis, Thomas P; Butler, Lisa M; Goldstein, David; McCarroll, Joshua A; Phillips, Phoebe A.
Afiliação
  • Kokkinos J; Pancreatic Cancer Translational Research Group, School of Medical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
  • Sharbeen G; Australian Centre for Nanomedicine, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, UNSW Sydney, Sydney, NSW, Australia.
  • Haghighi KS; Pancreatic Cancer Translational Research Group, School of Medical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
  • Ignacio RMC; Prince of Wales Hospital, Prince of Wales Clinical School, UNSW Sydney, Sydney, NSW, Australia.
  • Kopecky C; Pancreatic Cancer Translational Research Group, School of Medical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
  • Gonzales-Aloy E; Pancreatic Cancer Translational Research Group, School of Medical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
  • Youkhana J; Pancreatic Cancer Translational Research Group, School of Medical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
  • Timpson P; Pancreatic Cancer Translational Research Group, School of Medical Sciences, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
  • Pereira BA; Cancer Theme, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW, Australia.
  • Ritchie S; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia.
  • Pandzic E; Cancer Theme, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW, Australia.
  • Boyer C; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia.
  • Davis TP; Cancer Theme, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW, Australia.
  • Butler LM; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia.
  • Goldstein D; Biomedical Imaging Facility, Mark Wainwright Analytical Centre, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
  • McCarroll JA; Australian Centre for Nanomedicine, UNSW Sydney, Sydney, NSW, Australia.
  • Phillips PA; Centre for Advanced Macromolecular Design, School of Chemical Engineering, UNSW Sydney, Sydney, NSW, Australia.
Sci Rep ; 11(1): 1944, 2021 01 21.
Article em En | MEDLINE | ID: mdl-33479301
ABSTRACT
The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is attributed to the highly fibrotic stroma and complex multi-cellular microenvironment that is difficult to fully recapitulate in pre-clinical models. To fast-track translation of therapies and to inform personalised medicine, we aimed to develop a whole-tissue ex vivo explant model that maintains viability, 3D multicellular architecture, and microenvironmental cues of human pancreatic tumours. Patient-derived surgically-resected PDAC tissue was cut into 1-2 mm explants and cultured on gelatin sponges for 12 days. Immunohistochemistry revealed that human PDAC explants were viable for 12 days and maintained their original tumour, stromal and extracellular matrix architecture. As proof-of-principle, human PDAC explants were treated with Abraxane and we observed different levels of response between patients. PDAC explants were also transfected with polymeric nanoparticles + Cy5-siRNA and we observed abundant cytoplasmic distribution of Cy5-siRNA throughout the PDAC explants. Overall, our novel model retains the 3D architecture of human PDAC and has advantages over standard organoids presence of functional multi-cellular stroma and fibrosis, and no tissue manipulation, digestion, or artificial propagation of organoids. This provides unprecedented opportunity to study PDAC biology including tumour-stromal interactions and rapidly assess therapeutic response to drive personalised treatment.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adenocarcinoma / Organoides / Técnicas de Cultura de Células / Carcinoma Ductal Pancreático Limite: Humans Idioma: En Revista: Sci Rep Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Austrália
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adenocarcinoma / Organoides / Técnicas de Cultura de Células / Carcinoma Ductal Pancreático Limite: Humans Idioma: En Revista: Sci Rep Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Austrália