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- Title
Adipose Tissue-Derived Mesenchymal Stem Cells Extend the Lifespan and Enhance Liver Function in Hepatocyte Organoids.
- Authors
Ock, Sun A; Kim, Seo-Yeon; Ju, Won Seok; Kim, Young-Im; Wi, Ha-Yeon; Lee, Poongyeon
- Abstract
In this study, we generated hepatocyte organoids (HOs) using frozen-thawed primary hepatocytes (PHs) within a three-dimensional (3D) Matrigel dome culture in a porcine model. Previously studied hepatocyte organoid analogs, spheroids, or hepatocyte aggregates created using PHs in 3D culture systems have limitations in their in vitro lifespans. By co-culturing adipose tissue-derived mesenchymal stem cells (A-MSCs) with HOs within a 3D Matrigel dome culture, we achieved a 3.5-fold increase in the in vitro lifespan and enhanced liver function compared to a conventional two-dimensional (2D) monolayer culture, i.e., more than twice that of the HO group cultured alone, reaching up to 126 d. Although PHs were used to generate HOs, we identified markers associated with cholangiocyte organoids such as cytokeratin 19 and epithelial cellular adhesion molecule (EPCAM). Co-culturing A-MSCs with HOs increased the secretion of albumin and urea and glucose consumption compared to HOs cultured alone. After more than 100 d, we observed the upregulation of tumor protein P53 (TP53)-P21 and downregulation of EPCAM, albumin (ALB), and cytochrome P450 family 3 subfamily A member 29 (CYP3A29). Therefore, HOs with function and longevity improved through co-culturing with A-MSCs can be used to create large-scale human hepatotoxicity testing models and precise livestock nutrition assessment tools.
- Subjects
MESENCHYMAL stem cells; LONGEVITY; ORGANOIDS; ANIMAL nutrition; TUMOR proteins; P53 protein; KERATIN
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 20, p15429
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms242015429