Microchamber Cultures of Bladder Cancer: A Platform for Characterizing Drug Responsiveness and Resistance in PDX and Primary Cancer Cells

Gheibi, Pantea; Zeng, Shuxiong; Son, Kyung Jin; Vu, Tam; Hong, Ai; Dall′Era, Marc; Yap, Stanley A.; White, Ralph W. de Vere; Pan, Chong Xian; Revzin, Alexander

doi:10.1038/s41598-017-12543-9

Cited by 25 publications

(33 citation statements)

References 46 publications

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“…After the cells were patterned in collagen gel, the whole chip was submerged in medium for on-chip 3D cell culture. PDMS chambers have been proved to be suitable for 3D cell culture due to the oxygen permeability of PDMS 32 . The coverslip was also carefully slid aside for nutrient and oxygen exchange (Figure S2 ).…”

Section: Resultsmentioning

confidence: 99%

Large-scale patterning of single cells and cell clusters in hydrogels

Gong

Mills

2018

Sci Rep

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Biophysical properties of the extracellular matrix (ECM) are known to play a significant role in cell behavior. To gain a better understanding of the effects of the biophysical microenvironment on cell behavior, the practical challenge is longitudinally monitoring behavioral variations within a population to make statistically powerful assessments. Population-level measurements mask heterogeneity in cell responses, and large-scale individual cell measurements are often performed in a one-time, snapshot manner after removing cells from their matrix. Here we present an easy and low-cost method for large-scale, longitudinal studies of heterogeneous cell behavior in 3D hydrogel matrices. Using a platform we term “the drop-patterning chip”, thousands of cells were simultaneously transferred from microwell arrays and fully embedded, only using the force of gravity, in precise patterns in 3D collagen I or Matrigel. This method allows for throughputs approaching 2D patterning methods that lack phenotypic information on cell-matrix interactions, and does not rely on special equipment and cell treatments that may result in a proximal stiff surface. With a large and yet well-organized group of cells captured in 3D matrices, we demonstrated the capability of locating selected individual cells and monitoring cell division, migration, and proliferation for multiple days.

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Section: Resultsmentioning

confidence: 99%

Large-scale patterning of single cells and cell clusters in hydrogels

Gong

Mills

2018

Sci Rep

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“…While PDX models have many advantages in preclinical bladder cancer research, their lengthy development time and variable take rates (in addition to other limitations described above) preclude many researchers from using them. To address this limitation, Gheibi et al [45] successfully established cultures of PDX-derived ellipsoids in microchambers, which could help to maintain these patient-derived cells for extended periods of time. Ellipsoids demonstrated considerable heterogeneity in drug susceptibility, reflective of heterogeneity that may be seen in vivo [45].…”

Section: Patient-derived Xenografts (Pdx) Provide An Additional In VImentioning

confidence: 99%

“…To address this limitation, Gheibi et al [45] successfully established cultures of PDX-derived ellipsoids in microchambers, which could help to maintain these patient-derived cells for extended periods of time. Ellipsoids demonstrated considerable heterogeneity in drug susceptibility, reflective of heterogeneity that may be seen in vivo [45].…”

Section: Patient-derived Xenografts (Pdx) Provide An Additional In VImentioning

confidence: 99%

Modeling Tumor Heterogeneity in Bladder Cancer: The Current State of the Field and Future Needs

Seyer

Lehman

DeGraff

2019

BLC

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BACKGROUND: Tumor heterogeneity has been recognized in many cancer types for decades. However, the significance of tumor heterogeneity on disease course and clinical outcome in bladder cancer is of more recent interest to researchers and clinicians. This is especially true as morphologic and molecular heterogeneity has the potential to confound accurate diagnosis, efficient prognostication, and subsequent clinical management. While this is true, it is not always clear what laboratory models are available or suitable for the study of these important clinical phenomena. OBJECTIVE: To review in vitro and in vivo laboratory models for the study of morphologic and molecular tumor heterogeneity in bladder cancer. METHODS: We undertook a review of PubMed with a focus on identifying suitable models for the study of tumor heterogeneity in bladder cancer. RESULTS: We provide a review of common in vivo (genetically engineered mice and patient-derived xenografts) and in vitro (established cell lines and organoid systems) models and discuss their utility in the study of morphologic and molecular tumor heterogeneity in bladder cancer. CONCLUSION: Genetically engineered mouse models and patient-derived xenografts provide complementary approaches for the study of tumor heterogeneity in bladder cancer. In addition, cell culture-based systems provide a system amenable to genetic manipulation and mechanistic studies, while organoid systems bridge the gap between in vivo and in vitro systems. However, the availability of models to study molecular heterogeneity is limited, partly because of a relative lack of molecular characterization of available models. In summary, while models for the study of specific subsets of morphologic heterogeneity are available, more models are required for studies of molecular heterogeneity. This shortcoming could be partially addressed by more comprehensively characterizing currently available model systems. In addition, each system/approach has advantages and disadvantages, and care should be taken when selecting a given model.

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“…The common prediction model of tumor drug resistance has been used in recent years to establish a biological model based on tumor tissues such as transplanting tumor tissue or purified tumor cells into nude mice to observe the chemotherapeutic responses. However, due to the low success rate, high costs and time required to establish the biological model, the clinical application of this method is limited . Cell line models are another essential preclinical tumor model that can only be used to examine drug sensitivity by evaluating of the metabolic activity of cells through methyl tetrazolium (MTT) assays, as a reflection of cell viability.…”

Section: Introductionmentioning

confidence: 99%

“…However, due to the low success rate, high costs and time required to establish the biological model, the clinical application of this method is limited . Cell line models are another essential preclinical tumor model that can only be used to examine drug sensitivity by evaluating of the metabolic activity of cells through methyl tetrazolium (MTT) assays, as a reflection of cell viability. RNA sequencing is another commonly used method to predict drug sensitivity by detecting multiple drug resistance genes.…”

Section: Introductionmentioning

confidence: 99%

An optical study of drug resistance detection in endometrial cancer cells by dynamic and quantitative phase imaging

Tian

Cao

Xiao

et al. 2019

Journal of Biophotonics

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Platinum chemosensitivity detection plays a vital role during endometrial cancer treatment because chemotherapy responses have profound influences on patient's prognosis. Although several methods can be used to detect drug resistance characteristics, studies on detecting drug sensitivity based on dynamic and quantitative phase imaging of cancer cells are rare. In this study, digital holographic microscopy was applied to distinguish drug‐resistant and nondrug‐resistant endometrial cancer cells. Based on the reconstructed phase images, temporal evolutions of cell height (CH), cell projected area (CPA) and cell volume were quantitatively measured. The results show that change rates of CH and CPA were significantly different between drug‐resistant and nondrug‐resistant endometrial cancer cells. Furthermore, the results demonstrate that morphological characteristics have the potential to be utilized to distinguish the drug sensitivity of endometrial cancer cells, and it may provide new perspectives to establish optical methods to detect drug sensitivity and guide chemotherapy in endometrial cancer.

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Microchamber Cultures of Bladder Cancer: A Platform for Characterizing Drug Responsiveness and Resistance in PDX and Primary Cancer Cells

Cited by 25 publications

References 46 publications

Large-scale patterning of single cells and cell clusters in hydrogels

Large-scale patterning of single cells and cell clusters in hydrogels

Modeling Tumor Heterogeneity in Bladder Cancer: The Current State of the Field and Future Needs

An optical study of drug resistance detection in endometrial cancer cells by dynamic and quantitative phase imaging

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