The Ex Vivo Organ Culture of Bone

Staines, Katherine; Brown, Genevieve; Farquharson, Colin

doi:10.1007/978-1-4939-8997-3_10

Cited by 8 publications

(4 citation statements)

References 32 publications

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“…To overcome the aforementioned limitations, bone organ cultures are used, where harvested bone tissue is placed in a nutrient-rich medium, allowing it to remain viable and functional for several days to weeks. (52)(53)(54) These cultures were used to study processes including bone growth, remodeling, and repair. (52,55,56) Here bone cell interaction can be studied in the absence of confounding factors present in vivo.…”

Section: Bone Organ Culturementioning

confidence: 99%

Why Animal Experiments Are Still Indispensable in Bone Research: A Statement by the European Calcified Tissue Society

Stein,

Elefteriou,

Busse

et al. 2023

J of Bone & Mineral Res

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Major achievements in bone research have always relied on animal models and in vitro systems derived from patient and animal material. However, the use of animals in research has drawn intense ethical debate and the complete abolition of animal experimentation is demanded by fractions of the population. This phenomenon is enhanced by the reproducibility crisis in science and the advance of in vitro and in silico techniques. 3D culture, organ‐on‐a‐chip, and computer models have improved enormously over the last few years. Nevertheless, the overall complexity of bone tissue cross‐talk and the systemic and local regulation of bone physiology can often only be addressed in entire vertebrates. Powerful genetic methods such as conditional mutagenesis, lineage tracing, and modeling of the diseases enhanced the understanding of the entire skeletal system. In this review endorsed by the European Calcified Tissue Society (ECTS), a working group of investigators from Europe and the US provides an overview of the strengths and limitations of experimental animal models, including rodents, fish, and large animals, as well the potential and shortcomings of in vitro and in silico technologies in skeletal research. We propose that the proper combination of the right animal model for a specific hypothesis and state‐of‐the‐art in vitro and/or in silico technology is essential to solving remaining important questions in bone research. This is crucial for executing most efficiently the 3R principles to reduce, refine, and replace animal experimentation, for enhancing our knowledge of skeletal biology, and for the treatment of bone diseases that affect a large part of society. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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Section: Bone Organ Culturementioning

confidence: 99%

Why Animal Experiments Are Still Indispensable in Bone Research: A Statement by the European Calcified Tissue Society

Stein,

Elefteriou,

Busse

et al. 2023

J of Bone & Mineral Res

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show abstract

“…To date, several approaches to culture ex vivo models have been proposed, including tissue slices and explant cultures. Although these methods have been applied to different fields of research [ 137 , 138 ], there are still technical problems and limitations to take into account ( Figure 3 ) [ 139 ].…”

Section: Metastasis Process and Bone Metastatic Microenvironmentmentioning

confidence: 99%

Trends in Bone Metastasis Modeling

Laranga

Duchi

Ibrahim

et al. 2020

Cancers

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Bone is one of the most common sites for cancer metastasis. Bone tissue is composed by different kinds of cells that coexist in a coordinated balance. Due to the complexity of bone, it is impossible to capture the intricate interactions between cells under either physiological or pathological conditions. Hence, a variety of in vivo and in vitro approaches have been developed. Various models of tumor–bone diseases are routinely used to provide valuable information on the relationship between metastatic cancer cells and the bone tissue. Ideally, when modeling the metastasis of human cancers to bone, models would replicate the intra-tumor heterogeneity, as well as the genetic and phenotypic changes that occur with human cancers; such models would be scalable and reproducible to allow high-throughput investigation. Despite the continuous progress, there is still a lack of solid, amenable, and affordable models that are able to fully recapitulate the biological processes happening in vivo, permitting a correct interpretation of results. In the last decades, researchers have demonstrated that three-dimensional (3D) methods could be an innovative approach that lies between bi-dimensional (2D) models and animal models. Scientific evidence supports that the tumor microenvironment can be better reproduced in a 3D system than a 2D cell culture, and the 3D systems can be scaled up for drug screening in the same way as the 2D systems thanks to the current technologies developed. However, 3D models cannot completely recapitulate the inter- and intra-tumor heterogeneity found in patients. In contrast, ex vivo cultures of fragments of bone preserve key cell–cell and cell–matrix interactions and allow the study of bone cells in their natural 3D environment. Moreover, ex vivo bone organ cultures could be a better model to resemble the human pathogenic metastasis condition and useful tools to predict in vivo response to therapies. The aim of our review is to provide an overview of the current trends in bone metastasis modeling. By showing the existing in vitro and ex vivo systems, we aspire to contribute to broaden the knowledge on bone metastasis models and make these tools more appealing for further translational studies.

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“…The effects of mechanical loading on ex vivo cultured bones have been investigated in numerous studies [ 8 ]. Ex vivo cultured fetal metatarsal bones are a well-established model for studying longitudinal bone growth and responsiveness to different growth-regulating factors, including insulin-like growth factor-I (IGF-1), glucocorticoids and radial shock waves [ 9 , 10 ]. Additionally, the fetal femur bone has a high density of growth plate chondrocytes, as visualized by histological staining, thus providing great potential for ex vivo studies of longitudinal bone growth [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Micromechanical Loading Studies in Ex Vivo Cultured Embryonic Rat Bones Enabled by a Newly Developed Portable Loading Device

Zhang,

Zaman,

Nava

et al. 2023

Ann Biomed Eng

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Mechanical loading has been described as having the potential to affect bone growth. In order to experimentally study the potential clinical applications of mechanical loading as a novel treatment to locally modulate bone growth, there is a need to develop a portable mechanical loading device enabling studies in small bones. Existing devices are bulky and challenging to transfer within and between laboratories and animal facilities, and they do not offer user-friendly mechanical testing across both ex vivo cultured small bones and in vivo animal models. To address this, we developed a portable loading device comprised of a linear actuator fixed within a stainless-steel frame equipped with suitable structures and interfaces. The actuator, along with the supplied control system, can achieve high-precision force control within the desired force and frequency range, allowing various load application scenarios. To validate the functionality of this new device, proof-of-concept studies were performed in ex vivo cultured rat bones of varying sizes. First, very small fetal metatarsal bones were microdissected and exposed to 0.4 N loading applied at 0.77 Hz for 30 s. When bone lengths were measured after 5 days in culture, loaded bones had grown less than unloaded controls (p < 0.05). Next, fetal rat femur bones were periodically exposed to 0.4 N loading at 0.77 Hz while being cultured ex vivo for 12 days. Interestingly, this loading regimen had the opposite effect on bone growth, i.e., loaded femur bones grew significantly more than unloaded controls (p < 0.001). These findings suggest that complex relationships between longitudinal bone growth and mechanical loading can be determined using this device. We conclude that our new portable mechanical loading device allows experimental studies in small bones of varying sizes, which may facilitate further preclinical studies exploring the potential clinical applications of mechanical loading.

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The Ex Vivo Organ Culture of Bone

Cited by 8 publications

References 32 publications

Why Animal Experiments Are Still Indispensable in Bone Research: A Statement by the European Calcified Tissue Society

Why Animal Experiments Are Still Indispensable in Bone Research: A Statement by the European Calcified Tissue Society

Trends in Bone Metastasis Modeling

Micromechanical Loading Studies in Ex Vivo Cultured Embryonic Rat Bones Enabled by a Newly Developed Portable Loading Device

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