
3D bioprinting of liver spheroids derived from human induced pluripotent stem cells sustain liver function and viability in vitro
2019; IOP Publishing; Volume: 12; Issue: 1 Linguagem: Inglês
10.1088/1758-5090/ab4a30
ISSN1758-5090
AutoresErnesto Goulart, Luiz C. Caires-Júnior, Kayque A. Telles-Silva, Bruno Henrique Silva Araújo, Silvana A. Rocco, Maurício L. Sforça, Irene Layane de Sousa, Gerson Shigeru Kobayashi, Camila Manso Musso, Amanda F. Assoni, Danyllo Oliveira, Élia Garcia Caldini, Silvano Raia, Peter I. Lelkes, Mayana Zatz,
Tópico(s)Liver physiology and pathology
ResumoThe liver is responsible for many metabolic, endocrine and exocrine functions. Approximately 2 million deaths per year are associated with liver failure. Modern 3D bioprinting technologies allied with autologous induced pluripotent stem cells (iPS)-derived grafts could represent a relevant tissue engineering approach to treat end stage liver disease patients. However, protocols that accurately recapitulates liver's epithelial parenchyma through bioprinting are still underdeveloped. Here we evaluated the impacts of using single cell dispersion (i.e. obtained from conventional bidimensional differentiation) of iPS-derived parenchymal (i.e. hepatocyte-like cells) versus using iPS-derived hepatocyte-like cells spheroids (i.e. three-dimensional cell culture), both in combination with non-parenchymal cells (e.g. mesenchymal and endothelial cells), into final liver tissue functionality. Single cell constructs showed reduced cell survival and hepatic function and unbalanced protein/amino acid metabolism when compared to spheroid printed constructs after 18 days in culture. In addition, single cell printed constructs revealed epithelial-mesenchymal transition, resulting in rapid loss of hepatocyte phenotype. These results indicates the advantage of using spheroid-based bioprinting, contributing to improve current liver bioprinting technology towards future regenerative medicine applications and liver physiology and disease modeling.
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