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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorGOULART, Ernesto
dc.contributor.authorCAIRES-JUNIOR, Luiz Carlos de
dc.contributor.authorTELLES-SILVA, Kayque Alves
dc.contributor.authorARAUJO, Bruno Henrique Silva
dc.contributor.authorKOBAYASHI, Gerson S.
dc.contributor.authorMUSSO, Camila Manso
dc.contributor.authorASSONI, Amanda Faria
dc.contributor.authorOLIVEIRA, Danyllo
dc.contributor.authorCALDINI, Elia
dc.contributor.authorGERSTENHABER, Jonathan A.
dc.contributor.authorRAIA, Silvano
dc.contributor.authorLELKES, Peter I.
dc.contributor.authorZATZ, Mayana
dc.identifier.citationSTEM CELL RESEARCH & THERAPY, v.10, n.1, article ID 258, 11p, 2019
dc.description.abstractBackground Liver organoid technology holds great promises to be used in large-scale population-based drug screening and in future regenerative medicine strategies. Recently, some studies reported robust protocols for generating isogenic liver organoids using liver parenchymal and non-parenchymal cells derived from induced pluripotent stem cells (iPS) or using isogenic adult primary non-parenchymal cells. However, the use of whole iPS-derived cells could represent great challenges for a translational perspective. Methods Here, we evaluated the influence of isogenic versus heterogenic non-parenchymal cells, using iPS-derived or adult primary cell lines, in the liver organoid development. We tested four groups comprised of all different combinations of non-parenchymal cells for the liver functionality in vitro. Gene expression and protein secretion of important hepatic function markers were evaluated. Additionally, liver development-associated signaling pathways were tested. Finally, organoid label-free proteomic analysis and non-parenchymal cell secretome were performed in all groups at day 12. Results We show that liver organoids generated using primary mesenchymal stromal cells and iPS-derived endothelial cells expressed and produced significantly more albumin and showed increased expression of CYP1A1, CYP1A2, and TDO2 while presented reduced TGF-beta and Wnt signaling activity. Proteomics analysis revealed that major shifts in protein expression induced by this specific combination of non-parenchymal cells are related to integrin profile and TGF-beta/Wnt signaling activity. Conclusion Aiming the translation of this technology bench-to-bedside, this work highlights the role of important developmental pathways that are modulated by non-parenchymal cells enhancing the liver organoid maturation.eng
dc.description.sponsorshipFAPESP [2013/08028-1]
dc.relation.ispartofStem Cell Research & Therapy
dc.subject3D cultureeng
dc.subject.otherpluripotent stem-cellseng
dc.titleAdult and iPS-derived non-parenchymal cells regulate liver organoid development through differential modulation of Wnt and TGF-betaeng
dc.rights.holderCopyright BMCeng
dc.subject.wosCell & Tissue Engineeringeng
dc.subject.wosCell Biologyeng
dc.subject.wosMedicine, Research & Experimentaleng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng, Ernesto:Univ Sao Paulo, Dept Genet & Evolutionary Biol, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CEL, Sao Paulo, SP, Brazil, Luiz Carlos de:Univ Sao Paulo, Dept Genet & Evolutionary Biol, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CEL, Sao Paulo, SP, Brazil, Kayque Alves:Univ Sao Paulo, Dept Genet & Evolutionary Biol, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CEL, Sao Paulo, SP, Brazil, Bruno Henrique Silva:Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, BR-13083970 Campinas, SP, Brazil, Gerson S.:Univ Sao Paulo, Dept Genet & Evolutionary Biol, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CEL, Sao Paulo, SP, Brazil, Camila Manso:Univ Sao Paulo, Dept Genet & Evolutionary Biol, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CEL, Sao Paulo, SP, Brazil, Amanda Faria:Univ Sao Paulo, Dept Genet & Evolutionary Biol, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CEL, Sao Paulo, SP, Brazil, Danyllo:Univ Sao Paulo, Dept Genet & Evolutionary Biol, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CEL, Sao Paulo, SP, Brazil, Jonathan A.:Temple Univ, Dept Bioengn, Philadelphia, PA 19122 USA, Peter I.:Temple Univ, Dept Bioengn, Philadelphia, PA 19122 USA, Mayana:Univ Sao Paulo, Dept Genet & Evolutionary Biol, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CEL, Sao Paulo, SP, Brazil
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Appears in Collections:

Artigos e Materiais de Revistas Científicas - FM/MCG
Departamento de Cirurgia - FM/MCG

Artigos e Materiais de Revistas Científicas - FM/MPT
Departamento de Patologia - FM/MPT

Artigos e Materiais de Revistas Científicas - LIM/59
LIM/59 - Laboratório de Biologia Celular

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