Methods for Culturing Human Femur Tissue Explants to Study Breast Cancer Cell Colonization of the Metastatic Niche

Templeton, Zachary S.; Bachmann, Michael; Alluri, Rajiv V.; Maloney, William J.; Contag, Christopher H.; King, Bonnie L.

doi:10.3791/52656

Cited by 18 publications

(19 citation statements)

References 47 publications

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“…have been employed to study breast cancer cell colonization of bone. (61) Collectively, these results demonstrate that the ex vivo bone-cancer organ models can be a useful tool to study the effects of cancer cells in bone and to predict the effects of pharmacologic interventions in both bone and cancer cells.…”

mentioning

confidence: 81%

“…For instance, the effects of breast cancer cell lines on bone were tested in ex vivo cancer–bone organ cultures, using a combination of histologic and gene expression analyses . Moreover, femur organ cultures have been employed to study breast cancer cell colonization of bone . Collectively, these results demonstrate that the ex vivo bone–cancer organ models can be a useful tool to study the effects of cancer cells in bone and to predict the effects of pharmacologic interventions in both bone and cancer cells.…”

Section: Use Of Ex Vivo Bone Organ Cultures For the Study Of Bone Biomentioning

confidence: 99%

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Ex Vivo Organ Cultures as Models to Study Bone Biology

Bellido

Delgado‐Calle

2020

JBMR Plus

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The integrity of the skeleton is maintained by the coordinated and balanced activities of the bone cells. Osteoclasts resorb bone, osteoblasts form bone, and osteocytes orchestrate the activities of osteoclasts and osteoblasts. A variety of in vitro approaches has been used in an attempt to reproduce the complex in vivo interactions among bone cells under physiological as well as pathological conditions and to test new therapies. Most cell culture systems lack the proper extracellular matrix, cellular diversity, and native spatial distribution of the components of the bone microenvironment. In contrast, ex vivo cultures of fragments of intact bone preserve key cell–cell and cell–matrix interactions and allow the study of bone cells in their natural 3D environment. Further, bone organ cultures predict the in vivo responses to genetic and pharmacologic interventions saving precious time and resources. Moreover, organ cultures using human bone reproduce human conditions and are a useful tool to test patient responses to therapeutic agents. Thus, these ex vivo approaches provide a platform to perform research in bone physiology and pathophysiology. In this review, we describe protocols optimized in our laboratories to establish ex vivo bone organ cultures and provide technical hints and suggestions. In addition, we present examples on how this technical approach can be employed to study osteocyte biology, drug responses in bone, cancer‐induced bone disease, and cross‐talk between bone and other organs © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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mentioning

confidence: 81%

Section: Use Of Ex Vivo Bone Organ Cultures For the Study Of Bone Biomentioning

confidence: 99%

Ex Vivo Organ Cultures as Models to Study Bone Biology

Bellido

Delgado‐Calle

2020

JBMR Plus

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“…Hydrogel, scaffold Breast, prostate, osteosarcoma (63)(64)(65) Chitosan-alginate Scaffold Prostate, glioblastoma, hepatocellular carcinoma (66,67) Hyaluronic acid Scaffold, hydrogel Renal cell carcinoma, MM (68,69) Bacterial nanocellulose Scaffold, hydrogel Neuroblastoma, osteosarcoma, prostate, renal cancer, breast (70,71) Native ECM Scaffold MM, breast (72,73) ECM/cartilaginous matrix/Matrigel Scaffold, hydrogel Breast (74) Chitosan (with or without HA or collagen) Scaffold Breast (75) Cell sheets over medical-grade polycaprolactone-tricalcium phosphate scaffold prostate (76) Synthetic materials Poly(ethylene) glycol Hydrogel Breast, prostate (77)(78)(79) Poly(ε-caprolactone) Hydrogel Breast, prostate, osteosarcoma, Ewing sarcoma (80)(81)(82) Poly(amino acid-)-based polymers Hydrogel Osteosarcoma (83) PLG (nonmineralized) and PLG mineralized with HA Scaffold Breast (84) Adapted with permission from Sitarski and colleagues. (33) BM = bone marrow; ECM = extracellular matrix; HA = hydroxyapatite; MM = multiple myeloma; PLG = poly(lactide-co-glycolide).…”

Section: Collagenmentioning

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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“…Such direct co‐cultures with BTFs are good for short‐term co‐cultures due to limited viability of BTFs. Moreover, as BCCs are given direct access to BTFs, these systems do not recapitulate initial metastatic events at the bone . In addition, such models usually do not allow investigator control of microenvironment factors making studies of the role of specific factors of the bone environment on metastatic cell homing and colonization relatively difficult.…”

Section: Biomimetic Strategies To Mimic the Bone Environmentmentioning

confidence: 99%

Biomimetic strategies to recapitulate organ specific microenvironments for studying breast cancer metastasis

2017

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The progression of breast cancer from the primary tumor setting to the metastatic setting is the critical event defining Stage IV disease, no longer considered curable. The microenvironment at specific organ sites is known to play a key role in influencing the ultimate fate of metastatic cells; yet microenvironmental mediated-molecular mechanisms underlying organ specific metastasis in breast cancer are not well understood. This review discusses biomimetic strategies employed to recapitulate metastatic organ microenvironments, particularly, bone, liver, lung and brain to elucidate the mechanisms dictating metastatic breast cancer cell homing and colonization. These biomimetic strategies include in vitro techniques such as biomaterial-based co-culturing techniques, microfluidics, organ-mimetic chips, bioreactor technologies, and decellularized matrices as well as cutting edge in vivo techniques to better understand the interactions between metastatic breast cancer cells and the stroma at the metastatic site. The advantages and disadvantages of these systems are discussed. In addition, how creation of biomimetic models will impact breast cancer metastasis research and their broad utility is explored.

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Methods for Culturing Human Femur Tissue Explants to Study Breast Cancer Cell Colonization of the Metastatic Niche

Cited by 18 publications

References 47 publications

Ex Vivo Organ Cultures as Models to Study Bone Biology

Ex Vivo Organ Cultures as Models to Study Bone Biology

In Vitro 3D Cultures to Reproduce the Bone Marrow Niche

Biomimetic strategies to recapitulate organ specific microenvironments for studying breast cancer metastasis

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