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Liver tissue engineering using induced pluripotent stem cells

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Author(s):
Ernesto da Silveira Goulart Guimarães
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB)
Defense date:
Examining board members:
Mayana Zatz; Peter Istvan Lelkes; Oswaldo Keith Okamoto; Silvano Mario Atilio Raia
Advisor: Mayana Zatz
Abstract

Currently, the only feasible alternative for patients with end-stage liver disease is total or partial liver transplantation. Due to the growing gap between available donors and patients in waiting list, the development new tissue engineering technologies have become a growing need. Induced pluripotent cells (iPS) are an attractive alternative to serve as cell source for tissue engineering applications due to their ability to differentiate into all cellular phenotypes. Among the main liver tissue engineering technologies, 3D bioprinting, hepatic organoids and decellularization/recellularization of biological matrixes have generated much expectation. Thus, this work aimed to evaluate the use of iPS cells in the development of the aforementioned technologies. In order to evaluate how to bioprint a functional liver tissue using iPS-derived cells, we tested the effect of printing a single cell dispersion of hepatocytes versus printing hepatic spheroids. Hepatic spheroids showed greater viability and liver function, due to preserved epithelial phenotype over time. The composition of non-parenchymal cells using iPS-derived cells or primary adult cells for hepatic organoid formation was tested. The results indicated that, using primary mesenchymal cells and iPS-derived endothelial cells, we obtained a more efficient hepatic maturation due to the inhibition of TGF-β? and modulation Wnt signaling pathway. Recellularization of rat aortic decellularized scaffold with iPS-derived cells displayed hepatic function over time in a bioreactor-assisted culture, but the results indicate the need for improvements in the recellularization protocol. In conclusion, this work demonstrated the feasibility of use of iPS-derived cells for liver tissue engineering approaches and contributed to the development of the investigated technologies in order to generate future therapeutic alternatives for patients in waiting list for liver transplantation (AU)

FAPESP's process: 15/14821-1 - Development of functional hepatic by-pass using iPSCs-derived cells
Grantee:Ernesto da Silveira Goulart Guimarães
Support Opportunities: Scholarships in Brazil - Doctorate