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Bioengineering the ameloblastoma tumour to study its effect on bone nodule formation.
Bakkalci, Deniz; Jay, Amrita; Rezaei, Azadeh; Howard, Christopher A; Haugen, Håvard Jostein; Pape, Judith; Kishida, Shosei; Kishida, Michiko; Jell, Gavin; Arnett, Timothy R; Fedele, Stefano; Cheema, Umber.
Afiliación
  • Bakkalci D; UCL Centre of 3D Models Health and Disease, Division of Surgery and Interventional Sciences, University College London, Charles Bell House, London, UK.
  • Jay A; University College London Hospitals, London, UK.
  • Rezaei A; Division of Surgery and Interventional Sciences, University College London, Royal Free Campus, London, UK.
  • Howard CA; Deparment of Physics & Astronomy, University College London, London, UK.
  • Haugen HJ; Department of Biomaterial Institute for Clinical Dentistry, University of Oslo, Oslo, Norway.
  • Pape J; UCL Centre of 3D Models Health and Disease, Division of Surgery and Interventional Sciences, University College London, Charles Bell House, London, UK.
  • Kishida S; Department of Biochemistry and Genetics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
  • Kishida M; Department of Biochemistry and Genetics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
  • Jell G; Division of Surgery and Interventional Sciences, University College London, Royal Free Campus, London, UK.
  • Arnett TR; Department of Cell and & Developmental Biology, University College London, London, UK.
  • Fedele S; Eastman Dental Institute, University College London, London, UK.
  • Cheema U; UCL Centre of 3D Models Health and Disease, Division of Surgery and Interventional Sciences, University College London, Charles Bell House, London, UK. u.cheema@ucl.ac.uk.
Sci Rep ; 11(1): 24088, 2021 12 16.
Article en En | MEDLINE | ID: mdl-34916549
ABSTRACT
Ameloblastoma is a benign, epithelial cancer of the jawbone, which causes bone resorption and disfigurement to patients affected. The interaction of ameloblastoma with its tumour stroma drives invasion and progression. We used stiff collagen matrices to engineer active bone forming stroma, to probe the interaction of ameloblastoma with its native tumour bone microenvironment. This bone-stroma was assessed by nano-CT, transmission electron microscopy (TEM), Raman spectroscopy and gene analysis. Furthermore, we investigated gene correlation between bone forming 3D bone stroma and ameloblastoma introduced 3D bone stroma. Ameloblastoma cells increased expression of MMP-2 and -9 and RANK temporally in 3D compared to 2D. Our 3D biomimetic model formed bone nodules of an average surface area of 0.1 mm2 and average height of 92.37 [Formula see text] 7.96 µm over 21 days. We demonstrate a woven bone phenotype with distinct mineral and matrix components and increased expression of bone formation genes in our engineered bone. Introducing ameloblastoma to the bone stroma, completely inhibited bone formation, in a spatially specific manner. Multivariate gene analysis showed that ameloblastoma cells downregulate bone formation genes such as RUNX2. Through the development of a comprehensive bone stroma, we show that an ameloblastoma tumour mass prevents osteoblasts from forming new bone nodules and severely restricted the growth of existing bone nodules. We have identified potential pathways for this inhibition. More critically, we present novel findings on the interaction of stromal osteoblasts with ameloblastoma.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Osteogénesis / Ameloblastoma / Neoplasias Maxilomandibulares / Células del Estroma / Ingeniería de Tejidos Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article País de afiliación: Reino Unido

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Osteogénesis / Ameloblastoma / Neoplasias Maxilomandibulares / Células del Estroma / Ingeniería de Tejidos Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2021 Tipo del documento: Article País de afiliación: Reino Unido