Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Adult and iPS-derived non-parenchymal cells regulate liver organoid development through differential modulation of Wnt and TGF-beta

Full text
Author(s):
Show less -
Goulart, Ernesto [1] ; de Caires-Junior, Luiz Carlos [1] ; Telles-Silva, Kayque Alves [1] ; Silva Araujo, Bruno Henrique [2] ; Kobayashi, Gerson S. [1] ; Musso, Camila Manso [1] ; Assoni, Amanda Faria [1] ; Oliveira, Danyllo [1] ; Caldini, Elia [3] ; Gerstenhaber, Jonathan A. [4] ; Raia, Silvano [5] ; Lelkes, Peter I. [4] ; Zatz, Mayana [1]
Total Authors: 13
Affiliation:
[1] Univ Sao Paulo, Dept Genet & Evolutionary Biol, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CEL, Sao Paulo, SP - Brazil
[2] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, BR-13083970 Campinas, SP - Brazil
[3] Univ Sao Paulo, Med Sch, Dept Pathol, Lab Cellular Biol, Sao Paulo, SP - Brazil
[4] Temple Univ, Dept Bioengn, Philadelphia, PA 19122 - USA
[5] Univ Sao Paulo, Med Sch, Dept Surg, Sao Paulo, SP - Brazil
Total Affiliations: 5
Document type: Journal article
Source: STEM CELL RESEARCH & THERAPY; v. 10, n. 1 AUG 15 2019.
Web of Science Citations: 1
Abstract

Background 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. (AU)

FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
Grantee:Mayana Zatz
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC