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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.date.accessioned2019-09-23T14:20:31Z-
dc.date.available2019-09-23T14:20:31Z-
dc.date.issued2019
dc.identifier.citationSTEM CELL RESEARCH & THERAPY, v.10, n.1, article ID 258, 11p, 2019
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/33567-
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.language.isoeng
dc.publisherBMCeng
dc.relation.ispartofStem Cell Research & Therapy
dc.rightsopenAccesseng
dc.subjectOrganoideng
dc.subjectLivereng
dc.subjectiPSeng
dc.subjectHepatocyteeng
dc.subject3D cultureeng
dc.subject.otherpluripotent stem-cellseng
dc.subject.otherhepatocyteseng
dc.subject.otherpathwayeng
dc.subject.othersignalseng
dc.subject.otherintegrinseng
dc.subject.otherdatabaseeng
dc.subject.othermeteng
dc.titleAdult and iPS-derived non-parenchymal cells regulate liver organoid development through differential modulation of Wnt and TGF-betaeng
dc.typearticleeng
dc.rights.holderCopyright BMCeng
dc.identifier.doi10.1186/s13287-019-1367-x
dc.identifier.pmid31416480
dc.subject.wosCell & Tissue Engineeringeng
dc.subject.wosCell Biologyeng
dc.subject.wosMedicine, Research & Experimentaleng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
hcfmusp.author.externalGOULART, Ernesto:Univ Sao Paulo, Dept Genet & Evolutionary Biol, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CEL, Sao Paulo, SP, Brazil
hcfmusp.author.externalCAIRES-JUNIOR, Luiz Carlos de:Univ Sao Paulo, Dept Genet & Evolutionary Biol, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CEL, Sao Paulo, SP, Brazil
hcfmusp.author.externalTELLES-SILVA, Kayque Alves:Univ Sao Paulo, Dept Genet & Evolutionary Biol, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CEL, Sao Paulo, SP, Brazil
hcfmusp.author.externalARAUJO, Bruno Henrique Silva:Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, BR-13083970 Campinas, SP, Brazil
hcfmusp.author.externalKOBAYASHI, Gerson S.:Univ Sao Paulo, Dept Genet & Evolutionary Biol, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CEL, Sao Paulo, SP, Brazil
hcfmusp.author.externalMUSSO, Camila Manso:Univ Sao Paulo, Dept Genet & Evolutionary Biol, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CEL, Sao Paulo, SP, Brazil
hcfmusp.author.externalASSONI, Amanda Faria:Univ Sao Paulo, Dept Genet & Evolutionary Biol, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CEL, Sao Paulo, SP, Brazil
hcfmusp.author.externalOLIVEIRA, Danyllo:Univ Sao Paulo, Dept Genet & Evolutionary Biol, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CEL, Sao Paulo, SP, Brazil
hcfmusp.author.externalGERSTENHABER, Jonathan A.:Temple Univ, Dept Bioengn, Philadelphia, PA 19122 USA
hcfmusp.author.externalLELKES, Peter I.:Temple Univ, Dept Bioengn, Philadelphia, PA 19122 USA
hcfmusp.author.externalZATZ, Mayana:Univ Sao Paulo, Dept Genet & Evolutionary Biol, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CEL, Sao Paulo, SP, Brazil
hcfmusp.description.articlenumber258
hcfmusp.description.issue1
hcfmusp.description.volume10
hcfmusp.origemWOS
hcfmusp.origem.idWOS:000481740100001
hcfmusp.origem.id2-s2.0-85071024306
hcfmusp.publisher.cityLONDONeng
hcfmusp.publisher.countryENGLANDeng
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dc.description.indexMEDLINEeng
dc.identifier.eissn1757-6512
hcfmusp.citation.scopus20-
hcfmusp.scopus.lastupdate2022-06-10-
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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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