Evidence of Adult Features and Functions of Hepatocytes Differentiated from Human Induced Pluripotent Stem Cells and Self-Organized as Organoids
| العنوان: | Evidence of Adult Features and Functions of Hepatocytes Differentiated from Human Induced Pluripotent Stem Cells and Self-Organized as Organoids |
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| المؤلفون: | Antonietta Messina, Eléanor Luce, Nassima Benzoubir, Mattia Pasqua, Ulysse Pereira, Lydie Humbert, Thibaut Eguether, Dominique Rainteau, Jean-Charles Duclos-Vallée, Cécile Legallais, Anne Dubart-Kupperschmitt |
| المساهمون: | INSERM UMR S1193, Federation Hospitalo Universitaire Hépatinov, Centre Hépatobiliaire, Biomécanique et Bioingénierie (BMBI), Université de Technologie de Compiègne (UTC)-Centre National de la Recherche Scientifique (CNRS), Federation Hospitalo Universitaire Hépatinov, Departement Hospitalo-Universitaire Hepatinov [Hôpital Paul Brousse - APHP], Hôpital Paul Brousse, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Federation Hospilao Universitaire Hépatinov, Dubart Kupperschmitt, Anne |
| المصدر: | Cells Cells, 2022, 11 (3), ⟨10.3390/cells11030537⟩ Cells, Vol 11, Iss 537, p 537 (2022) Cells; Volume 11; Issue 3; Pages: 537 |
| بيانات النشر: | HAL CCSD, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Adult, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, hepatic mature functions, QH301-705.5, [SDV]Life Sciences [q-bio], Induced Pluripotent Stem Cells, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Humans, Biology (General), detoxification, ComputingMilieux_MISCELLANEOUS, bile canaliculi network, bile acids, hiPSCs, liver organoids, hiPSC-derived hepatocytes, HLCs, self-assembling, metabolism, Liver Diseases, Cell Differentiation, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Medicine, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Organoids, [SDV] Life Sciences [q-bio], Hepatocytes |
| الوصف: | Background: Human-induced pluripotent stem cell-derived hepatocytes (iHeps) have been shown to have considerable potential in liver diseases, toxicity, and pharmacological studies. However, there is a growing need to obtain iHeps that are truly similar to primary adult hepatocytes in terms of morphological features and functions. We generated such human iHeps, self-assembled as organoids (iHep-Orgs). Methods: iPSC-derived hepatoblasts were self-assembled into spheroids and differentiated into mature hepatocytes modulating final step of differentiation. Results: In about four weeks of culture, the albumin secretion levels and the complete disappearance of α-fetoprotein from iHep-Orgs suggested the acquisition of a greater degree of maturation than those previously reported. The expression of apical transporters and bile acid secretion evidenced the acquisition of complex hepatocyte polarity as well as the development of a functional and well-defined bile canalicular network confirmed by computational analysis. Activities recorded for CYP450, UGT1A1, and alcohol dehydrogenase, response to hormonal stimulation, and glucose metabolism were also remarkable. Finally, iHep-Orgs displayed a considerable ability to detoxify pathological concentrations of lactate and ammonia. Conclusions: With features similar to those of primary adult hepatocytes, the iHep-Orgs thus produced could be considered as a valuable tool for the development and optimization of preclinical and clinical applications. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2073-4409 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2878c886225eae078098c84dbc7ff4ecTest https://hal.science/hal-03561619/documentTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2878c886225eae078098c84dbc7ff4ec |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20734409 |
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