3D bioprinting of liver spheroids derived from human induced pluripotent stem cells sustain liver function and viability in vitro

Author(s):Show less -

Goulart, Ernesto ^[1] ; de Caires-Junior, Luiz Carlos ^[1] ; Telles-Silva, Kayque Alves ^[1] ; Silva Araujo, Bruno Henrique ^[2] ; Rocco, Silvana Aparecida ^[2] ; Sforca, Mauricio ^[2] ; de Sousa, Irene Layane ^[2] ; Kobayashi, Gerson S. ^[1] ; Musso, Camila Manso ^[1] ; Assoni, Amanda Faria ^[1] ; Oliveira, Danyllo ^[1] ; Caldini, Elia ^[3] ; Raia, Silvano ^[4] ; Lelkes, Peter I. ^[5] ; Zatz, Mayana ^[1]

Affiliation

^[1] Univ Sao Paulo, Human Genome & Stem Cell Res Ctr HUG CEL, Dept Genet & Evolutionary Biol, Inst Biosci, Sao Paulo, SP - Brazil

^[2] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, BR-13083970 Campinas, SP - Brazil

^[3] Univ Sao Paulo, Lab Cellular Biol, Dept Pathol, Sch Med, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Dept Surg, Sch Med, Sao Paulo, SP - Brazil

^[5] Temple Univ, Dept Bioengn, Philadelphia, PA 19122 - USA

• Document type: Journal article
• Source: BIOFABRICATION; v. 12, n. 1 JAN 2020.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 17/16283-2 - Development of tissue bioengineering techniques for the functional reconstruction of ex vivo iPSC cell livers
• Grantee: Luiz Carlos de Caires Júnior
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 14/50931-3 - Aging and genetic disorders: genomics and metagenomics
• Grantee: Mayana Zatz
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 15/14821-1 - Development of functional hepatic by-pass using iPSCs derived cells
• Grantee: Ernesto da Silveira Goulart Guimarães
• Support type: Scholarships in Brazil - Doctorate