Affiliation:
1. School of Biomedical Sciences Faculty of Health, and Translational Research Institute (TRI) Queensland University of Technology (QUT) Brisbane QLD 4102 Australia
2. Australian Prostate Cancer Research Centre ‐ Queensland (APCRC‐Q) QUT Brisbane QLD 4102 Australia
3. Centre for Biomedical Technologies QUT Brisbane QLD 4000 Australia
4. Max Planck Queensland Centre Brisbane QLD 4059 Australia
5. Centre for Genomics and Personalised Health QUT Brisbane QLD 4102 Australia
6. School of Mechanical Medical and Process Engineering Engineering Faculty QUT Brisbane QLD 4000 Australia
Abstract
AbstractIncreasing evidence shows bone marrow (BM)‐adipocytes as a potentially important contributor in prostate cancer (PCa) bone metastases. However, a lack of relevant models has prevented the full understanding of the effects of human BM‐adipocytes in this microenvironment. It is hypothesized that the combination of tunable gelatin methacrylamide (GelMA)‐based hydrogels with the biomimetic culture of human cells would offer a versatile 3D platform to engineer human bone tumor microenvironments containing BM‐adipocytes. Human osteoprogenitors, adipocytes, and PCa cells are individually cultured in vitro in GelMA hydrogels, leading to mineralized, adipose, and PCa tumor 3D microtissues, respectively. Osteoblast mineralization and tumor spheroid formation are tailored by hydrogel stiffness with lower stiffnesses correlating with increased mineralization and tumor spheroid size. Upon coculture with tumor cells, BM‐adipocytes undergo morphological changes and delipidation, suggesting reciprocal interactions between the cell types. When brought in vivo, the mineralized and adipose microtissues successfully form a humanized fatty bone microenvironment, presenting, for the first time, with human adipocytes. Using this model, an increase in tumor burden is observed when human adipocytes are present, suggesting that adipocytes support early bone tumor growth. The advanced platform presented here combines natural aspects of the microenvironment with tunable properties useful for bone tumor research.
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials
Cited by
6 articles.
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