A humanised rat model of osteosarcoma reveals ultrastructural differences between bone and mineralised tumour tissue

Christoph A Lahr; Marietta Landgraf; Ferdinand Wagner; Amaia Cipitria; Inés Moreno-Jiménez; Onur Bas; Beat Schmutz; Christoph Meinert; Amanda Dos Santos Cavalcanti; Tomoji Mashimo; Yoshiki Miyasaka; Boris M Holzapfel; Abbas Shafiee; Jacqui A McGovern; Dietmar W Hutmacher

doi:10.1016/j.bone.2021.116018

A humanised rat model of osteosarcoma reveals ultrastructural differences between bone and mineralised tumour tissue

Bone. 2022 May:158:116018. doi: 10.1016/j.bone.2021.116018. Epub 2021 May 20.

Authors

Affiliations

¹ Centre in Transformative Biomimetics in Bioengineering, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Brisbane, QLD 4059, Australia; Musculoskeletal University Centre Munich, Department of Orthopedics and Trauma Surgery, University Hospital Munich, LMU, Marchioninistraße 15, 81377 Munich, Germany.
² Centre in Transformative Biomimetics in Bioengineering, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Brisbane, QLD 4059, Australia.
³ Musculoskeletal University Centre Munich, Department of Orthopedics and Trauma Surgery, University Hospital Munich, LMU, Marchioninistraße 15, 81377 Munich, Germany; Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Lindwurmstrasse 4, 80337 Munich, Germany.
⁴ Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1 OT Golm, 14476 Potsdam, Germany.
⁵ Centre in Transformative Biomimetics in Bioengineering, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Brisbane, QLD 4059, Australia; ARC Training Centre in Additive Biomanufacturing, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia.
⁶ Centre in Transformative Biomimetics in Bioengineering, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Brisbane, QLD 4059, Australia; Jamieson Trauma Institute, Royal Brisbane and Women's Hospital, Metro North Hospital and Health Service, Herston, QLD 4029, Australia.
⁷ Centre in Transformative Biomimetics in Bioengineering, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Brisbane, QLD 4059, Australia; School of Mechanical, Medical and Process Engineering, 2 George Street, Brisbane, QLD 4001, Australia.
⁸ Division of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
⁹ Laboratory of Reproductive Engineering, Institute of Experimental Animal Sciences, Osaka University Medical School, Osaka, Japan.
¹⁰ Musculoskeletal University Centre Munich, Department of Orthopedics and Trauma Surgery, University Hospital Munich, LMU, Marchioninistraße 15, 81377 Munich, Germany.
¹¹ Centre in Transformative Biomimetics in Bioengineering, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Brisbane, QLD 4059, Australia; Herston Biofabrication Institute, Metro North Hospital and Health Service, Brisbane, QLD 4029, Australia. Electronic address: [email protected].
¹² Centre in Transformative Biomimetics in Bioengineering, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Brisbane, QLD 4059, Australia; School of Mechanical, Medical and Process Engineering, 2 George Street, Brisbane, QLD 4001, Australia. Electronic address: [email protected].
¹³ Centre in Transformative Biomimetics in Bioengineering, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Brisbane, QLD 4059, Australia; ARC Training Centre in Additive Biomanufacturing, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia; School of Mechanical, Medical and Process Engineering, 2 George Street, Brisbane, QLD 4001, Australia. Electronic address: [email protected].

PMID: 34023543
DOI: 10.1016/j.bone.2021.116018

Abstract

Current xenograft animal models fail to accurately replicate the complexity of human bone disease. To gain translatable and clinically valuable data from animal models, new in vivo models need to be developed that mimic pivotal aspects of human bone physiology as well as its diseased state. Above all, an advanced bone disease model should promote the development of new treatment strategies and facilitate the conduction of common clinical interventional procedures. Here we describe the development and characterisation of an orthotopic humanised tissue-engineered osteosarcoma (OS) model in a recently genetically engineered x-linked severe combined immunodeficient (X-SCID) rat. For the first time in a genetically modified rat, our results show the successful implementation of an orthotopic humanised tissue-engineered bone niche supporting the growth of a human OS cell line including its metastatic spread to the lung. Moreover, we studied the inter- and intraspecies differences in ultrastructural composition of bone and calcified tissue produced by the tumour, pointing to the crucial role of humanised animal models.

Keywords: Animal model; Bone; Collagen; Humanised animal model; Orthotopic bone model; Osteosarcoma; Rat model; Tissue humanisation; Tumour; Ultrastructure.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Neoplasms* / secondary
Bone and Bones / pathology
Cell Line
Cell Line, Tumor
Humans
Osteosarcoma* / drug therapy
Rats
Tissue Engineering