Bioengineering a humanized 3D tri-culture osteosarcoma model to assess tumor invasiveness and therapy response
authors Monteiro, CF; Custodio, CA; Mano, JF
nationality International
journal ACTA BIOMATERIALIA
author keywords 3D in vitro tumor model; Osteosarcoma; Human platelet lysates; Co-culture; Drug screening
keywords MESENCHYMAL STEM-CELLS; IN-VITRO; OSTEOCYTE DIFFERENTIATION; MATRIX STIFFNESS; DRUG-DELIVERY; DOXORUBICIN; SPHEROIDS; STROMA; NANOPARTICLES; RESISTANCE
abstract To date, anticancer therapies with evidenced efficacy in preclinical models fail during clinical trials. The shortage of robust drug screening platforms that accurately predict patient's response underlie these misleading results. To provide a reliable platform for tumor drug discovery, we herein propose a rel-evant humanized 3D osteosarcoma (OS) model exploring the potential of methacryloyl platelet lysates (PLMA)-based hydrogels to sustain spheroid growth and invasion. The architecture and synergistic cell-microenvironment interaction of an invading tumor was recapitulated encapsulating spheroids in PLMA hydrogels, alone or co-cultured with osteoblasts and mesenchymal stem cells. The stem cells alignment toward OS spheroid suggested that tumor cells chemotactically attracted the surrounding stromal cells, which supported tumor growth and invasion into the hydrogels. The exposure of established models to doxorubicin revealed an improved drug resistance of PLMA-based models, comparing with scaffold-free spheroids. The proposed OS models highlighted the feasibility of PLMA hydrogels to support tumor in-vasion and recapitulate tumor-stromal cell crosstalk, demonstrating the potential of this 3D platform for complex tumor modelling. Statement of significance Cell invasion mechanisms involved in tumor progression have been recapitulated in the field of 3D in vitro modeling, leveraging the great advance in biomimetic materials. In line with the growing interest in human-derived biomaterials, the aim of this study is to explore for the first time the potential of methacryloyl platelet lysates (PLMA)-based hydrogels to develop a humanized 3D osteosarcoma model to assess tumor invasiveness and drug sensitivity. By co-culturing tumor spheroids with human osteoblasts and human mesenchymal stem cells, this study demonstrated the importance of the synergistic tumor cell-microenvironment interaction in tumor growth, invasion and drug resistance. The established 3D os-teosarcoma model highlighted the feasibility of PLMA hydrogels as a relevant 3D platform for complex tumor modelling. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
publisher ELSEVIER SCI LTD
issn 1742-7061
isbn 1878-7568
year published 2021
volume 134
beginning page 204
ending page 214
digital object identifier (doi) 10.1016/j.actbio.2021.07.034
web of science category 11
subject category Engineering, Biomedical; Materials Science, Biomaterials
unique article identifier WOS:000709956300004
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journal analysis (jcr 2019):
journal impact factor 7.242
5 year journal impact factor 7.502
category normalized journal impact factor percentile 89.769
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