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Development of functional hepatic by-pass using iPSCs derived cells

Grant number: 15/14821-1
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2015
Effective date (End): February 28, 2019
Field of knowledge:Biological Sciences - Genetics
Principal Investigator:Mayana Zatz
Grantee:Ernesto da Silveira Goulart Guimarães
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo, SP, Brazil
Associated research grant:13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center, AP.CEPID


The liver is a key organ in the regulation of metabolism and hemodynamics. Several acute and chronic liver diseases (i.e. resulting from toxic exposures or congenital diseases) progress for a severe loss of hepatic function. Currently, the only therapeutic option for patients with end-stage and/or progressively severe liver disease is the partial or total organ transplant. Due to the shortage of donors, risk of rejection and the need for post-surgical immunosuppressant therapies for long periods, liver tissue engineering aims to create effective alternatives that are able to provide secure functionality to the injured tissue. This project aims to develop an accessory functional liver tissue that function as a bypass vascular portal-cava. Decellularized Wistar rat aortas will be used as scaffolds where the tunica media will be recellularized with hepatocytes, the intima with endothelial cells and adventicia with mesenchymal cells. This process will be assisted and controlled by the bioreactor "Bioreactor Hollow Organs / ORCA (Harvard Apparatus)" on a protocol to be validated. The cells to be used shall be obtained by in vitro differentiation of human induced pluripotent cells (iPSCs), coming from the same healthy donor. The cell phenotype and functionality of all cell types in culture and after the repopulation /tissue neo-formation will be tested. The hypothesis is that this new accessory bioartificial liver tissue is able to meet in part the functional demands of an injured liver tissue, and may in the future serve as an alternative for patients on the waiting list for transplantation.

Articles published in Agência FAPESP about the scholarship:
Brazil will have the technology to transplant pig organs into humans  

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ARAUJO, BRUNO H. S.; KAID, CAROLINI; DE SOUZA, JANAINA S.; DA SILVA, SERGIO GOMES; GOULART, ERNESTO; CAIRES, LUIZ C. J.; MUSSO, CAMILA M.; TORRES, LAILA B.; FERRASA, ADRIANO; HERAI, ROBERTO; ZATZ, MAYANA; OKAMOTO, OSWALDO K.; CAVALHEIRO, ESPER A. Down Syndrome iPSC-Derived Astrocytes Impair Neuronal Synaptogenesis and the mTOR Pathway In Vitro. Molecular Neurobiology, v. 55, n. 7, p. 5962-5975, JUL 2018. Web of Science Citations: 2.
KAID, CAROLINI; GOULART, ERNESTO; CAIRES-JUNIOR, LUIZ C.; ARAUJO, BRUNO H. S.; SOARES-SCHANOSKI, ALESSANDRA; BUENO, HELOISA M. S.; TELLES-SILVA, KAYQUE A.; ASTRAY, RENATO M.; ASSONI, AMANDA F.; JUNIOR, ANTONIO F. R.; VENTINI, DANIELLA C.; PUGLIA, ANA L. P.; GOMES, ROSELANE P.; ZATZ, MAYANA; OKAMOTO, OSWALDO K. Zika Virus Selectively Kills Aggressive Human Embryonal CNS Tumor Cells In Vitro and In Vivo. Cancer Research, v. 78, n. 12, p. 3363-3374, JUN 15 2018. Web of Science Citations: 2.

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