3D Tumor Models in Urology

Neuhaus, Jochen; Rabien, Anja; Reinhold, Annabell; Koehler, Luzie; Berndt‐Paetz, Mandy

doi:10.3390/ijms24076232

Cited by 4 publications

(7 citation statements)

References 131 publications

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“…Many other organoid models have been successfully established for BCa research. The available model systems include porous scaffolds for mimicking a tissue-like microenvironment, 3D bioprinting and Organ(oid)-on-a-chip [29]. For instance, so-called bioprinters have been developed to enable the computer-assisted design and printing of 3D cancer models or whole organs, which allows for control of the cell distribution within the 3D structure [30].…”

Section: Discussionmentioning

confidence: 99%

“…This method also allows for co-cultures of different cell types, including cancer cells and stromal cells, without the influence of artificial ECM components. The system is suitable for high-throughput drug screening using microplate readers or confocal analysis systems [29]. The option to gradually expand this culture system, e.g., by the inclusion of immune cells to investigate basic immunological processes, is another exciting prospect.…”

Section: Discussionmentioning

confidence: 99%

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Cell Line-Based Human Bladder Organoids with Bladder-like Self-Organization—A New Standardized Approach in Bladder Cancer Research

Berndt-Paetz,

Han,

Weimann

et al. 2023

Biomedicines

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Three-dimensional tumor models have gained significant importance in bladder cancer (BCa) research. Organoids consisting of different cell types better mimic solid tumors in terms of 3D architecture, proliferation, cell–cell interaction and drug responses. We developed four organoids from human BCa cell lines with fibroblasts and smooth muscle cells of the bladder, aiming to find models for BCa research. The organoids were characterized in terms of cytokeratins, vimentin, α-actin and KI67 by immunoreactivity. Further, we studied ligand-dependent activation of the Wnt/β-catenin pathway and investigated the responses to anti-tumor therapies. The organoids mimicked the structure of an inverse bladder wall, with outside urothelial cells and a core of supportive cells. The cytokeratin staining patterns and proliferation rate were in conjunction with the origins of the BCa cells. RT-112 even showed stratification of the epithelium. Treatment with Wnt10B led to increased β-catenin (active) levels in high-grade organoids, but not in low-grade BCa cells. Doxorubicin treatment resulted in clearly reduced viability (10–30% vs. untreated). In contrast, the effectivity of radiotherapy depended on the proliferation status of BCa cells. In conclusion, cell-line-based organoids can form bladder-like structures and reproduce in vivo features such as urothelial differentiation and stratification. Thus, they can be useful tools for functional studies in BCa and anti-cancer drug development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cell Line-Based Human Bladder Organoids with Bladder-like Self-Organization—A New Standardized Approach in Bladder Cancer Research

Berndt-Paetz,

Han,

Weimann

et al. 2023

Biomedicines

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“…In the last 2 years, most research groups focused on the establishment of ‘organoids’ that are defined as 3D structures consisting of multiple types of cells [ 11 ]. Berndt-Paetz et al developed organoids containing either of the classical BC cell lines RT4, RT112, T24 or CAL-29, as well as primary human bladder fibroblasts and smooth muscle cells.…”

Section: In Vitro Modelsmentioning

confidence: 99%

Preclinical models for bladder cancer therapy research

Ertl,

Shariat,

Berger

et al. 2024

Current Opinion in Urology

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Purpose of review Bladder cancer (BC) is a highly heterogenous disease comprising tumours of various molecular subtypes and histologic variants. This heterogeneity represents a major challenge for the development of novel therapeutics. Preclinical models that closely mimic in vivo tumours and reflect their diverse biology are indispensable for the identification of therapies with specific activity in various BC subtypes. In this review, we summarize efforts and progress made in this context during the last 24 months. Recent findings In recent years, one main focus was laid on the development of patient-derived BC models. Patient-derived organoids (PDOs) and patient-derived xenografts (PDXs) were demonstrated to widely recapitulate the molecular and histopathological characteristics, as well as the drug response profiles of the corresponding tumours of origin. These models, thus, represent promising tools for drug development and personalized medicine. Besides PDXs, syngenic/allogenic in vivo models are of growing importance. Since these models are generated using immunocompetent hosts, they can, amongst others, be used to develop novel immunotherapeutics and to evaluate the impact of the immune system on drug response and resistance. Summary In the past two years, various in vivo and in vitro models closely recapitulating the biology and heterogeneity of human bladder tumours were developed.

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“…This, in turn, results in clinically relevant outcomes, such as testing the response to anticancer drugs [ 20 , 145 ]. These organoid models have been used for breast cancer cells [ 17 ], urological cancers [ 162 ], lung cancer [ 163 ], brain tissue [ 164 ], and many others [ 20 , 145 , 165 , 166 ]. Their strengths include the applicability to numerous research fields, from basic science to modelling diseases, including development and infectious diseases, drug discovery and screening, as well as personalized medicine [ 33 , 167 ].…”

Section: In Vitro Models Of Neuroblastomamentioning

confidence: 99%

Preclinical Models of Neuroblastoma—Current Status and Perspectives

Krawczyk

Kitlińska

2023

Cancers

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Preclinical in vitro and in vivo models remain indispensable tools in cancer research. These classic models, including two- and three-dimensional cell culture techniques and animal models, are crucial for basic and translational studies. However, each model has its own limitations and typically does not fully recapitulate the course of the human disease. Therefore, there is an urgent need for the development of novel, advanced systems that can allow for efficient evaluation of the mechanisms underlying cancer development and progression, more accurately reflect the disease pathophysiology and complexity, and effectively inform therapeutic decisions for patients. Preclinical models are especially important for rare cancers, such as neuroblastoma, where the availability of patient-derived specimens that could be used for potential therapy evaluation and screening is limited. Neuroblastoma modeling is further complicated by the disease heterogeneity. In this review, we present the current status of preclinical models for neuroblastoma research, discuss their development and characteristics emphasizing strengths and limitations, and describe the necessity of the development of novel, more advanced and clinically relevant approaches.

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3D Tumor Models in Urology

Cited by 4 publications

References 131 publications

Cell Line-Based Human Bladder Organoids with Bladder-like Self-Organization—A New Standardized Approach in Bladder Cancer Research

Cell Line-Based Human Bladder Organoids with Bladder-like Self-Organization—A New Standardized Approach in Bladder Cancer Research

Preclinical models for bladder cancer therapy research

Preclinical Models of Neuroblastoma—Current Status and Perspectives

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