Human iPSC-derived liver co-culture spheroids to model liver fibrosis.
Cools. Laura L; Dastjerd. Mina Kazemzadeh MK; Smout. Ayla A; Merens. Vincent V; Yang. Yuwei Y; Reynaert. Hendrik H; Messaoudi. Nouredin N; Smet. Vincent De V; Kumar. Manoj M; Verhulst. Stefaan S; Verfaillie. Catherine C; van Grunsven. Leo A LA
Key Findings
- iPSC‑derived liver cells can be combined into spheroids that mature over 21 days
- The spheroids show markers and drug‑toxicity responses similar to real human liver tissue
- The model can be used to study fibrosis mechanisms and test anti‑fibrotic drugs
Practical Outcomes
- For biohackers there’s no direct protocol to try; the work is a research tool for drug discovery, not a self‑experiment or supplement guidance.
Summary
This study describes a lab method to grow liver cells from stem cells in 3‑D clusters that mimic liver scarring, but it doesn’t give any advice you can use at home or any info about the peptide humanin.
Abstract
The lack of adequate human<i>in vitro</i>models that recapitulate the cellular composition and response of the human liver to injury hampers the development of anti-fibrotic drugs. The goal of this study was to develop a human spheroid culture model to study liver fibrosis by using induced pluripotent stem cell (iPSC)-derived liver cells. iPSCs were independently differentiated towards hepatoblasts (iHepatoblasts), hepatic stellate cells (iHSCs), endothelial cells (iECs) and macrophages (iMΦ), before assembly into free floating spheroids by culturing cells in 96-well U-bottom plates and orbital shaking for up to 21 days to allow further maturation. Through transcriptome analysis, we show further maturation of iECs and iMΦ, the differentiation of the iHepatoblasts towards hepatocyte-like cells (iHeps) and the inactivation of the iHSCs by the end of the 3D culture. Moreover, these cultures display a similar expression of cell-specific marker genes (<i>CYP3A4, PDGFRβ, CD31</i>and<i>CD68</i>) and sensitivity to hepatotoxicity as spheroids made using freshly isolated primary human liver cells. Furthermore, we show the functionality of the iHeps and the iHSCs by mimicking liver fibrosis through iHep-induced iHSC activation, using acetaminophen. In conclusion, we have established a reproducible human iPSC-derived liver culture model that can be used to mimic fibrosis<i>in vitro</i>as a replacement of primary human liver derived 3D models. The model can be used to investigate pathways involved in fibrosis development and to identify new targets for chronic liver disease therapy.
Study Information
pubmed
2024
2024-06-28T00:00:00.000Z
10.1088/1758-5090/ad5766
9
61