Comparative analysis of different three-dimensional culture systems to establish an in vitro bladder cancer model for toxicological assays

• Grant number: 15/05102-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: December 01, 2016
• End date: May 31, 2020
• Field of knowledge: Engineering - Chemical Engineering
• Principal Investigator: Kamilla Swiech Antonietto
• Grantee: Robson Luis Ferraz do Amaral
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The culture of mammalian is an important tool for the prediction of activity, metabolism and toxicity in vivo of therapeutic formulations. Almost all cells in the body are in three-dimensional (3D) environment that is essential for their growth and metabolism resulting from cell-cell and cell-matrix interactions. However, in traditional culture monolayer (2D) such interactions are considerably reduced. This property is critical in toxicological tests since environmental stimuli have a significant effect on the properties, functions and behaviour of cells that may affect the cellular response to the tested substances. In view of this, 3D cell cultures, unlike the monolayer 2D cultures, are capable of promoting a microenvironment that mimics the native microenvironment observed in tissues. Therefore, this project was proposed in order to evaluate the use of different forms of three-dimensional cell culture (3D) as a platform for in vitro cytotoxic assays. As a model, will be used bladder cancer cells (RT4) and drugs that have been commonly used for the treatment of this cancer. Cultures of spheroids will be evaluated using ultra-low attachment plates and hanging drop systems. For culture-based scaffolds it will be use microcarriers, biomembranes and hydrogels. Cytotoxicity assays employing Paclitaxel and Doxorubicin - drugs commonly used to treat bladder cancer - will be realized in 3D and 2D systems for comparative purposes with in vivo models. The best system for 3D cultivation will be determined taking into account the results of cytotoxicity and aspects of culture such as time, complexity, reliability, cost and possibility of application in high-throughput screening platforms. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DECARLI, MONIZE CAIADO; AMARAL, ROBSON; DOS SANTOS, DIOGO PERES; TOFANI, LARISSA BUENO; KATAYAMA, ERIC; REZENDE, RODRIGO ALVARENGA; LOPES DA SILVA, JORGE VICENTE; SWIECH, KAMILLA; TORRES SUAZO, CLAUDIO ALBERTO; MOTA, CARLOS; et al. ell spheroids as a versatile research platform: formation mechanisms, high throughput production, characterization and application. BIOFABRICATION, v. 13, n. 3, JUL 2021. (19/11950-6, 15/05102-1)

AMARAL, ROBSON; ZIMMERMANN, MAIKE; MA, AI-HONG; ZHANG, HONGYONG; SWIECH, KAMILLA; PAN, CHONG-XIAN. A Simple Three-Dimensional In Vitro Culture Mimicking the In Vivo-Like Cell Behavior of Bladder Patient-Derived Xenograft Models. CANCERS, v. 12, n. 5, MAY 2020. (15/05102-1)

DECARLI, MONIZE CAIADO; AMARAL, ROBSON; DOS SANTOS, DIOGO PERES; TOFANI, LARISSA BUENO; KATAYAMA, ERIC; REZENDE, RODRIGO ALVARENGA; LOPES DA SILVA, JORGE VICENTE; SWIECH, KAMILLA; TORRES SUAZO, CLAUDIO ALBERTO; MOTA, CARLOS; et al. Cell spheroids as a versatile research platform: formation mechanisms, high throughput production, characterization and applications. BIOFABRICATION, v. 13, n. 3, p. 37-pg., 2021-07-01. (15/05102-1, 19/11950-6)

AMARAL, ROBSON L. F.; MIRANDA, MARIZA; MARCATO, PRISCYLA D.; SWIECH, KAMILLA. Comparative Analysis of 3D Bladder Tumor Spheroids Obtained by Forced Floating and Hanging Drop Methods for Drug Screening. FRONTIERS IN PHYSIOLOGY, v. 8, AUG 22 2017. (15/05102-1)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

AMARAL, Robson Luis Ferraz do. Comparative analysis of different three-dimensional culture systems for the establishment of an in vitro bladder cancer model for therapeutic-efficacy assays. 2020. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.