دورية أكاديمية
Microencapsulated Hepatocytes Differentiated from Human Induced Pluripotent Stem Cells: Optimizing 3D Culture for Tissue Engineering Applications
| العنوان: | Microencapsulated Hepatocytes Differentiated from Human Induced Pluripotent Stem Cells: Optimizing 3D Culture for Tissue Engineering Applications |
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| المؤلفون: | Hussein, Marwa, Pasqua, Mattia, Pereira, Ulysse, Benzoubir, Nassima, Duclos-Vallée, Jean-Charles, Dubart-Kupperschmitt, Anne, Legallais, Cecile, Messina, Antonietta |
| المساهمون: | Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, DHU Hepatinov Villejuif, Biomécanique et Bioingénierie (BMBI), Université de Technologie de Compiègne (UTC)-Centre National de la Recherche Scientifique (CNRS), ANR-16-RHUS-0005,iLite,iLite(2016) |
| المصدر: | ISSN: 2073-4409 ; Cells ; https://hal.science/hal-04193769Test ; Cells, 2023, 12 (6), pp.865. ⟨10.3390/cells12060865⟩. |
| بيانات النشر: | HAL CCSD MDPI |
| سنة النشر: | 2023 |
| المجموعة: | Université de Technologie de Compiègne: HAL |
| مصطلحات موضوعية: | hiPSCs, hiPSC-derived hepatocytes, alginate microencapsulation, 3D culture conditions, hepatocyte functions, hepatocyte maturation, encapsulated iHep organoids, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials |
| الوصف: | International audience ; Liver cell therapy and in vitro models require functional human hepatocytes, the sources of which are considerably limited. Human induced pluripotent stem cells (hiPSCs) represent a promising and unlimited source of differentiated human hepatocytes. However, when obtained in two-dimensional (2D) cultures these hepatocytes are not fully mature and functional. As three-dimensional culture conditions offer advantageous strategies for differentiation, we describe here a combination of three-dimensional (3D) approaches enabling the successful differentiation of functional hepatocytes from hiPSCs by the encapsulation of hiPSC-derived hepatoblasts in alginate beads of preformed aggregates. The resulting encapsulated and differentiated hepatocytes (E-iHep-Orgs) displayed a high level of albumin synthesis associated with the disappearance of α-fetoprotein (AFP) synthesis, thus demonstrating that the E-iHep-Orgs had reached a high level of maturation, similar to that of adult hepatocytes. Gene expression analysis by RT-PCR and immunofluorescence confirmed this maturation. Further functional assessments demonstrated their enzymatic activities, including lactate and ammonia detoxification, as well as biotransformation activities of Phase I and Phase II enzymes. This study provides proof of concept regarding the benefits of combining three-dimensional techniques (guided aggregation and microencapsulation) with liver differentiation protocols as a robust approach to generate mature and functional hepatocytes that offer a permanent and unlimited source of hepatocytes. Based on these encouraging results, our combined conditions to produce mature hepatocytes from hiPSCs could be extended to liver tissue engineering and bioartificial liver (BAL) applications at the human scale for which large biomasses are mandatory. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/36980206; hal-04193769; https://hal.science/hal-04193769Test; https://hal.science/hal-04193769/documentTest; https://hal.science/hal-04193769/file/Husseincells-12-00865.pdfTest; PUBMED: 36980206; PUBMEDCENTRAL: PMC10047414 |
| DOI: | 10.3390/cells12060865 |
| الإتاحة: | https://doi.org/10.3390/cells12060865Test https://hal.science/hal-04193769Test https://hal.science/hal-04193769/documentTest https://hal.science/hal-04193769/file/Husseincells-12-00865.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.EE6B2F88 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/cells12060865 |
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