Decellularized Liver Nanofibers Enhance and Stabilize the Long-Term Functions of Primary Human Hepatocytes In Vitro.

Autor: Liu JS; Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, IL, 60607, USA., Madruga LYC; Department of Chemical & Biological Engineering, Colorado State University, Fort Collins, CO, 80523-1370, USA., Yuan Y; Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, IL, 60607, USA., Kipper MJ; Department of Chemical & Biological Engineering, Colorado State University, Fort Collins, CO, 80523-1370, USA., Khetani SR; Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, IL, 60607, USA.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2023 Jul; Vol. 12 (19), pp. e2202302. Date of Electronic Publication: 2023 Apr 10.
DOI: 10.1002/adhm.202202302
Abstrakt: Owing to significant differences across species in liver functions, in vitro human liver models are used for screening the metabolism and toxicity of compounds, modeling diseases, and cell-based therapies. However, the extracellular matrix (ECM) scaffold used for such models often does not mimic either the complex composition or the nanofibrous topography of native liver ECM. Thus, here novel methods are developed to electrospin decellularized porcine liver ECM (PLECM) and collagen I into nano- and microfibers (≈200-1000 nm) without synthetic polymer blends. Primary human hepatocytes (PHHs) on nanofibers in monoculture or in coculture with nonparenchymal cells (3T3-J2 embryonic fibroblasts or primary human liver endothelial cells) display higher albumin secretion, urea synthesis, and cytochrome-P450 1A2, 2A6, 2C9, and 3A4 enzyme activities than on conventionally adsorbed ECM controls. PHH functions are highest on the collagen/PLECM blended nanofibers (up to 34-fold higher CYP3A4 activity relative to adsorbed ECM) for nearly 7 weeks in the presence of the fibroblasts. In conclusion, it is shown for the first time that ECM composition and topography synergize to enhance and stabilize PHH functions for several weeks in vitro. The nanofiber platform can prove useful for the above applications and to elucidate cell-ECM interactions in the human liver.
(© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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