Development of tissue bioengineering techniques for the functional reconstruction of ex vivo iPSC cell livers

• Grant number: 17/16283-2
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): March 01, 2018
• Effective date (End): November 30, 2021
• Field of knowledge: Biological Sciences - Biology
• Principal researcher: Mayana Zatz
• Grantee: Luiz Carlos de Caires Júnior
• 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 an important organ with several essential functions for keeping the hysiological homeostasis. Currently, the liver transplantation is an alternative therapy to patients with irreversible hepatic injuries. This process is complex due limited available donors, as well as the difficulty of immunological compatibility. Considering the stem-cells differentiation abilities towardseveral cell-types and methodological advances to the enrichment and use of the ultrastructureof decellularized organ matrices for repopulation (organs reconstruction by cell perfusion), the aim of this work is the development and improvement of bioengineering methods which could allow the ex vivo reconstruction of a functional liver. For that, livers from Wistar rats (250-300g)will be descellularized. The liver matrices (extracellular matrix ultrastructure) will be enriched with proteins from human liver cells conditioned medium (CM). Similarly, hepatoblastos, hepatocytes endothelial cells and MSCs will be differentiated from iPSCs for recellularization of decellularized liver matrices. The recellularization procedure will be evaluated by immunohistochemistry and thefunctionality of the new organ will assessed by dosaging of liver cell molecules yield.

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: 0.

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.