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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 researcher: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

Abstract

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.

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Scientific publications (6)
(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)
CHEN, NA; ZHAO, SEN; JOLLY, ANGAD; WANG, LIANLEI; PAN, HONGXIN; YUAN, JIAN; CHEN, SHAOKE; KOCH, ANDRE; MA, CONGCONG; TIAN, WEIJIE; JIA, ZIQI; KANG, JIA; ZHAO, LINA; QIN, CHENGLU; FAN, XIN; RALL, KATHARINA; COBAN-AKDEMIR, ZEYNEP; CHEN, ZEFU; JHANGIANI, SHALINI; LIANG, ZE; NIU, YUCHEN; LI, XIAOXIN; YAN, ZIHUI; WU, YONG; DONG, SHUANGSHUANG; SONG, CHENGCHENG; QIU, GUIXING; ZHANG, SHUYANG; LIU, PENGFEI; POSEY, JENNIFER E.; ZHANG, FENG; LUO, GUANGNAN; WU, ZHIHONG; SU, JIANZHONG; ZHANG, JIANGUO; CHEN, EUGENIA Y.; ROUSKAS, KONSTANTINOS; GLENTIS, STAVROS; BACOPOULOU, FLORA; DELIGEOROGLOU, EFTHYMIOS; CHROUSOS, GEORGE; LYONNET, STANISLAS; POLAK, MICHEL; ROSENBERG, CARLA; DINGELDEIN, IRENE; BONILLA, XIMENA; BOREL, CHRISTELLE; GIBBS, RICHARD A.; DIETRICH, JENNIFER E.; DIMAS, ANTIGONE S.; ANTONARAKIS, STYLIANOS E.; BRUCKER, SARA Y.; LUPSKI, JAMES R.; WU, NAN; ZHU, LAN; SC, DECIPHERING DISORDERS INVOLVING. Perturbations of genes essential for Mullerian duct and Wolffian duct development in Mayer-Rokitansky-Kuster-Hauser syndrome. American Journal of Human Genetics, v. 108, n. 2, p. 337-345, FEB 4 2021. Web of Science Citations: 1.
OLIVEIRA, DANYLLO; MORALES-VICENTE, DAVID A.; AMARAL, MURILO S.; LUZ, LIVIA; SERTIE, ANDREA L.; LEITE, FELIPE S.; NAVARRO, CLAUDIA; KAID, CAROLINI; ESPOSITO, JOYCE; GOULART, ERNESTO; CAIRES, LUIZ; ALVES, LUCIANA M.; MELO, UIRA S.; FIGUEIREDO, THALITA; MITNE-NETO, MIGUEL; OKAMOTO, OSWALDO K.; VERJOVSKI-ALMEIDA, SERGIO; ZATZ, MAYANA. Different gene expression profiles in iPSC-derived motor neurons from ALS8 patients with variable clinical courses suggest mitigating pathways for neurodegeneration. Human Molecular Genetics, v. 29, n. 9, p. 1465-1475, MAY 1 2020. Web of Science Citations: 2.
GOULART, ERNESTO; DE CAIRES-JUNIOR, LUIZ CARLOS; TELLES-SILVA, KAYQUE ALVES; SILVA ARAUJO, BRUNO HENRIQUE; ROCCO, SILVANA APARECIDA; SFORCA, MAURICIO; DE SOUSA, IRENE LAYANE; KOBAYASHI, GERSON S.; MUSSO, CAMILA MANSO; ASSONI, AMANDA FARIA; OLIVEIRA, DANYLLO; CALDINI, ELIA; RAIA, SILVANO; LELKES, PETER I.; ZATZ, MAYANA. 3D bioprinting of liver spheroids derived from human induced pluripotent stem cells sustain liver function and viability in vitro. BIOFABRICATION, v. 12, n. 1 JAN 2020. Web of Science Citations: 0.
RIVAS, MARIA PRATES; MARQUES AGUIAR, TALITA FERREIRA; FERNANDES, GUSTAVO RIBEIRO; CAIRES, LUIZ CARLOS; GOULART, ERNESTO; TELLES-SILVA, KAYQUE ALVES; CYPRIANO, MONICA; CAMINADA DE TOLEDO, SILVIA REGINA; ROSENBERG, CARLA; CARRARO, DIRCE MARIA; LIMA DA COSTA, CECILIA MARIA; DA CUNHA, ISABELA WERNECK; VICTORINO KREPISCHI, ANA CRISTINA. TET Upregulation Leads to 5-Hydroxymethylation Enrichment in Hepatoblastoma. FRONTIERS IN GENETICS, v. 10, JUN 12 2019. Web of Science Citations: 1.
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: 6.
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: 6.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
. Liver tissue engineering using induced pluripotent stem cells. 2019. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB) São Paulo.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.