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Goulart E , de Caires-Junior LC , Telles-Silva KA , Araujo BHS , Rocco SA , Sforca M , de Sousa IL , Kobayashi GS , Musso CM , Assoni AF , Oliveira D , Caldini E , Raia S , Lelkes PI , Zatz M
3D bioprinting of liver spheroids derived from human induced pluripotent stem cells sustain liver function and viability in vitro
Biofabrication. 2019 Nov 27;12(1) :015010
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Abstract
The 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.
Notes
1758-5090 Goulart, Ernesto de Caires-Junior, Luiz Carlos Telles-Silva, Kayque Alves Araujo, Bruno Henrique Silva Orcid: 0000-0003-0012-4217 Rocco, Silvana Aparecida Sforca, Mauricio de Sousa, Irene Layane Kobayashi, Gerson Shigeru Orcid: 0000-0002-6520-5774 Musso, Camila Manso Assoni, Amanda Faria Oliveira, Danyllo Caldini, Elia Raia, Silvano Lelkes, Peter I Zatz, Mayana Orcid: 0000-0003-3970-8025 Journal Article England Biofabrication. 2019 Oct 2. doi: 10.1088/1758-5090/ab4a30.