دورية أكاديمية
Investigation of the hepatic development in the coculture of hiPSCs-derived LSECs and HLCs in a fluidic microenvironment
العنوان: | Investigation of the hepatic development in the coculture of hiPSCs-derived LSECs and HLCs in a fluidic microenvironment |
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المؤلفون: | Mathieu Danoy, Yannick Tauran, Stephane Poulain, Rachid Jellali, Johanna Bruce, Marjorie Leduc, Morgane Le Gall, Yuta Koui, Hiroshi Arakawa, Francoise Gilard, Bertrand Gakiere, Yukio Kato, Charles Plessy, Taketomo Kido, Atsushi Miyajima, Yasuyuki Sakai, Eric Leclerc |
المصدر: | APL Bioengineering, Vol 5, Iss 2, Pp 026104-026104-13 (2021) |
بيانات النشر: | AIP Publishing LLC, 2021. |
سنة النشر: | 2021 |
المجموعة: | LCC:Biotechnology LCC:Medical technology |
مصطلحات موضوعية: | Biotechnology, TP248.13-248.65, Medical technology, R855-855.5 |
الوصف: | Interactions between the different liver cell types are critical to the maintenance or induction of their function in vitro. In this work, human-induced Pluripotent Stem Cells (hiPSCs)-derived Liver Sinusoidal Endothelial Cells (LSECs) and Hepatocytes-Like Cells (HLCs) were cultured and matured in a microfluidic environment. Both cell populations were differentiated in Petri dishes, detached, and inoculated in microfluidic biochips. In cocultures of both cell types, the tissue has exhibited a higher production of albumin (3.19 vs 5.31 μg/mL/106 cells in monocultures and cocultures) as well as a higher inducibility CYP450 over monocultures of HLCs. Tubular-like structures composed of LSECs and positive for the endothelial marker PECAM1, as well as a tissue more largely expressing Stabilin-2 were detected in cocultures only. In contrast, monocultures exhibited no network and less specific endothelial markers. The transcriptomic analysis did not reveal a marked difference between the profiles of both culture conditions. Nevertheless, the analysis allowed us to highlight different upstream regulators in cocultures (SP1, EBF1, and GATA3) and monocultures (PML, MECP2, and NRF1). In cocultures, the multi-omics dataset after 14 days of maturation in biochips has shown the activation of signaling related to hepatic maturation, angiogenesis, and tissue repair. In this condition, inflammatory signaling was also found to be reduced when compared to monocultures as illustrated by the activation of NFKB and by the detection of several cytokines involved in tissue injury in the latter. Finally, the extracted biological processes were discussed regarding the future development of a new generation of human in vitro hepatic models. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2473-2877 |
العلاقة: | https://doaj.org/toc/2473-2877Test |
DOI: | 10.1063/5.0041227 |
الوصول الحر: | https://doaj.org/article/e70436d4d10a4e2393e6907ba57b1f84Test |
رقم الانضمام: | edsdoj.70436d4d10a4e2393e6907ba57b1f84 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 24732877 |
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DOI: | 10.1063/5.0041227 |