3D bone models to study the complex physical and cellular interactions between tumor and the bone microenvironment

Vanderburgh, Joseph P.; Guelcher, Scott A.; Sterling, Julie A.

doi:10.1002/jcb.26774

Cited by 17 publications

(11 citation statements)

References 57 publications

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“…Furthermore, more sophisticated in vitro techniques are being developed that more accurately model the bone. For example, 3D bone mimicking scaffolds have been synthesized based on human bone structure from microCT scans and these scaffolds can be seeded with tumor cells and bone‐resident cells, such as mesenchymal stem cells, to study their interactions; the scaffolds recapitulate the rigidity and structural nuances of trabecular bone and thus have advantages over 2D co‐culture models . These scaffold cultures can be used for many applications and can even be sectioned for histological analysis.…”

Section: Introductionmentioning

confidence: 99%

Tumor dormancy in bone

Mayhew¹,

Omokehinde²,

Johnson

2019

Cancer Reports

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Background Bone marrow is a common site of metastasis for a number of tumor types, including breast, prostate, and lung cancer, but the mechanisms controlling tumor dormancy in bone are poorly understood. In breast cancer, while advances in drug development, screening practices, and surgical techniques have dramatically improved survival rates in recent decades, metastatic recurrence in the bone remains common and can develop years or decades after elimination of the primary tumor. Recent Findings It is now understood that tumor cells disseminate to distant metastatic sites at early stages of tumor progression, leaving cancer survivors at a high risk of recurrence. This review will discuss mechanisms of bone lesion development and current theories of how dormant cancer cells behave in bone, as well as a number of processes suspected to be involved in the maintenance of and exit from dormancy in the bone microenvironment. Conclusions The bone is a complex microenvironment with a multitude of cell types and processes. Many of these factors, including angiogenesis, immune surveillance, and hypoxia, are thought to regulate tumor cell entry and exit from dormancy in different bone marrow niches.

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Section: Introductionmentioning

confidence: 99%

Tumor dormancy in bone

Mayhew¹,

Omokehinde²,

Johnson

2019

Cancer Reports

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“…The resulting scaffold demonstrates a mineral content comparable to that of human bone, within which human bone marrow-derived stem cells attach, proliferate, and differentiate into active mineralizing osteoblasts and survive in coculture with seeded cancer cells. (27,28) Recently, novel approaches to material design have created diverse structures upon and within which a cellular niche, including a cancer-bone cell niche, might be created. The development of 3D-microfiber scaffolds using melt electrowriting technology (MEW) is one approach capable of mimicking both the structural and chemical environment.…”

Section: Culture Model Systemsmentioning

confidence: 99%

“…The bonelike construct is formed through the 3D printing of the polyurethane–hydroxyapatite material using defined patterns based upon μCT scanning of human trabecular bone. The resulting scaffold demonstrates a mineral content comparable to that of human bone, within which human bone marrow‐derived stem cells attach, proliferate, and differentiate into active mineralizing osteoblasts and survive in coculture with seeded cancer cells …”

Section: Introductionmentioning

confidence: 99%

Modeling the Human Bone–Tumor Niche: Reducing and Replacing the Need for Animal Data

Rao

Edwards

2020

JBMR Plus

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Bone is the most common site for cancer metastasis. Understanding the interactions within the complex, heterogeneous bone–tumor microenvironment is essential for the development of new therapeutics. Various animal models of tumor‐induced bone disease are routinely used to provide valuable information on the relationship between cancer cells and the skeleton. However, new model systems exist that offer an alternative approach to the use of animals and might more accurately reveal the cellular interactions occurring within the human bone–tumor niche. This review highlights replacement models that mimic the bone microenvironment and where cancer metastases and tumor growth might be assessed alongside bone turnover. Such culture models include the use of calcified regions of animal tissue and scaffolds made from bone mineral hydroxyapatite, synthetic polymers that can be manipulated during manufacture to create structures resembling trabecular bone surfaces, gel composites that can be modified for stiffness and porosity to resemble conditions in the tumor–bone microenvironment. Possibly the most accurate model system involves the use of fresh human bone samples, which can be cultured ex vivo in the presence of human tumor cells and demonstrate similar cancer cell–bone cell interactions as described in vivo. In addition, the use of mathematical modeling and computational biology approaches provide an alternative to preliminary animal testing. The use of such models offers the capacity to mimic significant elements of the human bone–tumor environment, and complement, refine, or replace the use of preclinical models. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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“…Investigations of bone mechanics are necessary to fully understand how the mechanical properties of the bone microenvironment (BMev) influence the biological functions such as bone turnover, and have been well developed in recent decades. In-vitro models mimicking the BMev are commonly used to study the role of mechanical properties in bone function and related diseases, such as cancer-induced bone metastasis (9, 10). However, these in vitro models do not fully recapitulate the complexity of the in vivo BMev and hence lack fundamental components of the underlying biology (10).…”

Section: Introductionmentioning

confidence: 99%

“…In-vitro models mimicking the BMev are commonly used to study the role of mechanical properties in bone function and related diseases, such as cancer-induced bone metastasis (9, 10). However, these in vitro models do not fully recapitulate the complexity of the in vivo BMev and hence lack fundamental components of the underlying biology (10).…”

Section: Introductionmentioning

confidence: 99%

Mechanical Heterogeneity in the Bone Microenvironment as Characterised by Atomic Force Microscopy

Hobbs

Chen

Mullin

et al. 2020

Preprint

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Bones are structurally heterogeneous organs with diverse functions that undergo mechanical stimuli across multiple length scales. Mechanical characterisation of the bone microenvironment is important for understanding how bones function in health and disease. Here we describe the mechanical architecture of cortical bone, the growth plate, metaphysis and marrow in fresh murine bones, probed using atomic force microscopy in physiological buffer. Both elastic and viscoelastic properties are found to be highly heterogeneous with moduli ranging over 3 to 5 orders of magnitude, both within and across regions. All regions include extremely soft areas, with moduli of a few Pascal and viscosities as low as tens Pa⋅s. Aging impacts the viscoelasticity of the bone marrow strongly but has limited effect on the other regions studied. Our approach provides the opportunity to explore the mechanical properties of complex tissues at the length scale relevant to cellular processes and how these impact on aging and disease.SIGNIFICANCEThe mechanical properties of biological materials at cellular scale are involved in guiding cell fate. However, there is a critical gap in our knowledge of such properties in complex tissues. The physiochemical environment surrounding the cells in in-vitro studies differs significantly from that found in vivo. Existing mechanical characterisation of real tissues are largely limited to properties at larger scales, structurally simple (e.g. epithelial monolayers) or non-intact (e.g. through fixation) tissues. In this paper, we address this critical gap and present the micro-mechanical properties of the relatively intact bone microenvironment. The measured Young’s moduli and viscosity provide a sound guidance in bioengineering designs. The striking heterogeneity at supracellular scale reveals the potential contribution of the mechanical properties in guiding cell behaviour.

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3D bone models to study the complex physical and cellular interactions between tumor and the bone microenvironment

Cited by 17 publications

References 57 publications

Tumor dormancy in bone

Tumor dormancy in bone

Modeling the Human Bone–Tumor Niche: Reducing and Replacing the Need for Animal Data

Mechanical Heterogeneity in the Bone Microenvironment as Characterised by Atomic Force Microscopy

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