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Updated: Jun 13, 2025
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Human Liver Spheroids from Peripheral Blood for Liver Disease Studies
Published on: January 27, 2023
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Framework nucleic Acid-MicroRNA mediated hepatic differentiation and functional hepatic spheroid development for
Hongyan Wei1,2,3,4, Tiantian Xue1, Fenfang Li1
1Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, Guangdong, China.
Bioactive Materials
|September 16, 2024
Summary
MicroRNA 122 effectively directs adipose stem cells to become liver cells, creating functional liver organoids. This novel approach shows promise for treating acute liver failure with enhanced cell therapy and organoid models.
Area of Science:
- Regenerative Medicine
- Stem Cell Biology
- Hepatology
Background:
- Inducing hepatic differentiation is crucial for liver cell therapies and acute liver failure (ALF) treatment.
- MicroRNAs have shown significant potential in regenerative medicine applications.
- Current methods for generating functional hepatocytes from stem cells face challenges.
Purpose of the Study:
- To develop a microRNA-based strategy for hepatic differentiation of adipose-derived mesenchymal stem cells (ADMSCs).
- To generate functional hepatocyte-like cells (FNA-miR-122-iHep) and liver organoids (Hep:HUE-liver spheroids).
- To evaluate the therapeutic efficacy of these cells and organoids in treating ALF.
Main Methods:
- Utilized microRNA 122-functionalized tetrahedral framework nucleic acid (FNA-miR-122) to direct ADMSC differentiation.
- Co-cultured FNA-miR-122-iHep with human umbilical vein endothelial cells (HUVECs) to synthesize liver organoids.
- Performed transcriptome analysis to understand molecular mechanisms and assessed therapeutic efficacy in ALF models.
Main Results:
- Successfully generated functional hepatocyte-like cells (FNA-miR-122-iHep) from ADMSCs.
- Established functional liver organoids (Hep:HUE-liver spheroids) with enhanced hepatocyte maturation and tissue-specific functions.
- Demonstrated high therapeutic efficacy of both FNA-miR-122-iHep and Hep:HUE-liver spheroids in treating ALF in vivo.
Conclusions:
- A robust microRNA-based system was established for inducing ADMSCs into functional hepatocytes and generating hepatic organoids.
- This approach offers a cost-effective method for producing cells and organoids for ALF therapy.
- The findings promise a highly efficient therapeutic strategy for acute liver failure using engineered cells and organoids.
