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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Cell spheroids as a versatile research platform: formation mechanisms, high throughput production, characterization and applications

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Decarli, Monize Caiado [1, 2] ; Amaral, Robson [3] ; dos Santos, Diogo Peres [4] ; Tofani, Larissa Bueno [3] ; Katayama, Eric [4] ; Rezende, Rodrigo Alvarenga [5] ; Lopes da Silva, Jorge Vicente [5] ; Swiech, Kamilla [3] ; Torres Suazo, Claudio Alberto [4] ; Mota, Carlos [2] ; Moroni, Lorenzo [2] ; Moraes, Angela Maria [1]
Total Authors: 12
[1] Univ Estadual Campinas, Sch Chem Engn, Dept Engn Mat & Bioproc, Av Albert Einstein 500, BR-13083852 Campinas, SP - Brazil
[2] Maastricht Univ, MERLN Inst Technol Inspired Regenerat Med, Dept Complex Tissue Regenerat, Univ Singel 40, NL-6229 ER Maastricht - Netherlands
[3] Univ Sao Paulo, Dept Pharmaceut Sci, Sch Pharmaceut Sci Ribeirao Preto, Ave Cafe, BR-14040903 Ribeirao Preto, SP - Brazil
[4] Univ Fed Sao Carlos, Dept Chem Engn, Rod Washington Luiz SP 310, Km 235, BR-13565905 Sao Carlos, SP - Brazil
[5] Renato Archer Informat Technol Ctr CTI, Rod Dom Pedro I SP 65, Km 143, 6, BR-3069901 Campinas, SP - Brazil
Total Affiliations: 5
Document type: Review article
Source: BIOFABRICATION; v. 13, n. 3 JUL 2021.
Web of Science Citations: 0

Three-dimensional (3D) cell culture has tremendous advantages to closely mimic the in vivo architecture and microenvironment of healthy tissue and organs, as well as of solid tumors. Spheroids are currently the most attractive 3D model to produce uniform reproducible cell structures as well as a potential basis for engineering large tissues and complex organs. In this review we discuss, from an engineering perspective, processes to obtain uniform 3D cell spheroids, comparing dynamic and static cultures and considering aspects such as mass transfer and shear stress. In addition, computational and mathematical modeling of complex cell spheroid systems are discussed. The non-cell-adhesive hydrogel-based method and dynamic cell culture in bioreactors are focused in detail and the myriad of developed spheroid characterization techniques is presented. The main bottlenecks and weaknesses are discussed, especially regarding the analysis of morphological parameters, cell quantification and viability, gene expression profiles, metabolic behavior and high-content analysis. Finally, a vast set of applications of spheroids as tools for in vitro study model systems is examined, including drug screening, tissue formation, pathologies development, tissue engineering and biofabrication, 3D bioprinting and microfluidics, together with their use in high-throughput platforms. (AU)

FAPESP's process: 19/11950-6 - Biofabrication Studies for Osteochondral Structure
Grantee:Jorge Vicente Lopes da Silva
Support type: Regular Research Grants
FAPESP's process: 15/05102-1 - Comparative analysis of different three-dimensional culture systems to establish an in vitro bladder cancer model for toxicological assays
Grantee:Robson Luis Ferraz do Amaral
Support type: Scholarships in Brazil - Doctorate (Direct)