Human ex vivo 3D bone model recapitulates osteocyte response to metastatic prostate cancer

Choudhary, Saba; Ramasundaram, Poornema; Dziopa, Eugenia; Mannion, Ciaran; Kissin, Yair; Tricoli, Lucas; Albanese, Christopher; Lee, Woo; Zilberberg, Jenny

doi:10.1038/s41598-018-36424-x

Cited by 37 publications

(32 citation statements)

References 59 publications

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“…However, these cultures are also used to investigate bone and cartilage metabolism or bone defect healing. When co-cultured with cancer cells this model was used to investigate bone metastases [88][89][90][91][92]. Similarly, a co-culture of this model with immune cells was used to investigate inflammatory bone diseases [93].…”

Section: Ex Vivo Bone Culturesmentioning

confidence: 99%

Feasibility of Cell Lines for In Vitro Co-Cultures Models for Bone Metabolism

et al. 2020

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Today, over 70 diseases and health conditions are known that negatively affect the bone quality directly or indirectly by their medical treatment, establishing the term metabolic bone disease. Already every third hospitalized patient in Europe suffers from musculoskeletal injuries or diseases. Facing an ageing society and a more and more sedentary lifestyle the number of chronic diseases and consequently metabolic bone diseases are expected to continuously increase. In order to investigate the various disease constellations and/or develop new treatment strategies suitable models representing bone metabolism are required. Many in vivo, ex vivo and in vitro models have been described, which have their advantages and limits. We here summarize the advantages and challenges of frequently used models to investigate bone metabolism, focusing on in vitro co-cultures of bone forming osteoblasts and osteoclasts. Comparing own data with published models, we further elaborate the feasibility of commonly used cells lines for such in vitro co-culture models, in order to provide an easy, constantly available, and up-scalable model system for screening alterations in bone metabolism.

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Section: Ex Vivo Bone Culturesmentioning

confidence: 99%

Feasibility of Cell Lines for In Vitro Co-Cultures Models for Bone Metabolism

et al. 2020

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“…Choudhary and colleagues used a 3D network of primary human osteocytes to create an engineered bone tissue model to study the interaction of PCa cells with bone. Unlike 2D cultures, this 3D model showed an increase in expression of fibroblast growth factor 23 and alkaline phosphatase, accurately depicting the bone niche observed clinically in metastatic PCa . The use of polymer‐nanoclay‐based 3D scaffolds for the growth and study of PCa cells in coculture with MSCs yielded the formation of tumoroids with tight cellular junctions and hypoxic cores.…”

Section: Bone Cancer Applications Of 3d Bone Modelsmentioning

confidence: 79%

“…Unlike 2D cultures, this 3D model showed an increase in expression of fibroblast growth factor 23 and alkaline phosphatase, accurately depicting the bone niche observed clinically in metastatic PCa. (106) The use of polymer-nanoclay-based 3D scaffolds for the growth and study of PCa cells in coculture with MSCs yielded the formation of tumoroids with tight cellular junctions and hypoxic cores. The hypoxia was found to increase angiogenesis.…”

Section: Leukemiamentioning

confidence: 99%

In Vitro 3D Cultures to Reproduce the Bone Marrow Niche

et al. 2019

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Over the past century, the study of biological processes in the human body has progressed from tissue culture on glass plates to complex 3D models of tissues, organs, and body systems. These dynamic 3D systems have allowed for more accurate recapitulation of human physiology and pathology, which has yielded a platform for disease study with a greater capacity to understand pathophysiology and to assess pharmaceutical treatments. Specifically, by increasing the accuracy with which the microenvironments of disease processes are modeled, the clinical manifestation of disease has been more accurately reproduced in vitro. The application of these models is crucial in all realms of medicine, but they find particular utility in diseases related to the complex bone marrow niche. Osteoblast, osteoclasts, bone marrow adipocytes, mesenchymal stem cells, and red and white blood cells represent some of cells that call the bone marrow microenvironment home. During states of malignant marrow disease, neoplastic cells migrate to and join this niche. These cancer cells both exploit and alter the niche to their benefit and to the patient's detriment. Malignant disease of the bone marrow, both primary and secondary, is a significant cause of morbidity and mortality today. Innovative study methods are necessary to improve patient outcomes. In this review, we discuss the evolution of 3D models and compare them to the preceding 2D models. With a specific focus on malignant bone marrow disease, we examine 3D models currently in use, their observed efficacy, and their potential in developing improved treatments and eventual cures. Finally, we comment on the aspects of 3D models that must be critically examined as systems continue to be optimized so that they can exert greater clinical impact in the future. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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“…However, these cultures can also be used for investigating bone and cartilage metabolism or bone defect healing. When co-cultured with other cells, e.g., cancer cells or immune cells, even for investigating bone metastases (Choudhary et al 2018 ; Curtin et al 2012 ; Marino et al 2019 ; Salamanna et al 2016 ; Salih 2019 ) or inflammatory bone diseases (Sloan et al 2013 ).…”

Section: Models To Investigate Bone Quality and Functionmentioning

confidence: 99%

Use of in vitro bone models to screen for altered bone metabolism, osteopathies, and fracture healing: challenges of complex models

et al. 2020

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Approx. every third hospitalized patient in Europe suffers from musculoskeletal injuries or diseases. Up to 20% of these patients need costly surgical revisions after delayed or impaired fracture healing. Reasons for this are the severity of the trauma, individual factors, e.g, the patients’ age, individual lifestyle, chronic diseases, medication, and, over 70 diseases that negatively affect the bone quality. To investigate the various disease constellations and/or develop new treatment strategies, many in vivo, ex vivo, and in vitro models can be applied. Analyzing these various models more closely, it is obvious that many of them have limits and/or restrictions. Undoubtedly, in vivo models most completely represent the biological situation. Besides possible species-specific differences, ethical concerns may question the use of in vivo models especially for large screening approaches. Challenging whether ex vivo or in vitro bone models can be used as an adequate replacement for such screenings, we here summarize the advantages and challenges of frequently used ex vivo and in vitro bone models to study disturbed bone metabolism and fracture healing. Using own examples, we discuss the common challenge of cell-specific normalization of data obtained from more complex in vitro models as one example of the analytical limits which lower the full potential of these complex model systems.

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Human ex vivo 3D bone model recapitulates osteocyte response to metastatic prostate cancer

Cited by 37 publications

References 59 publications

Feasibility of Cell Lines for In Vitro Co-Cultures Models for Bone Metabolism

Feasibility of Cell Lines for In Vitro Co-Cultures Models for Bone Metabolism

In Vitro 3D Cultures to Reproduce the Bone Marrow Niche

Use of in vitro bone models to screen for altered bone metabolism, osteopathies, and fracture healing: challenges of complex models

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