Framework nucleic Acid-MicroRNA mediated hepatic differentiation and functional hepatic spheroid development for treating acute liver failure  

作　　者：Hongyan Wei Tiantian Xue Fenfang Li Enguo Ju Haixia Wang Mingqiang Li Yu Tao 

机构地区：[1]Laboratory of Biomaterials and Translational Medicine,Center for Nanomedicine,The Third Affiliated Hospital,Sun Yat-sen University,Guangzhou,510630,Guangdong,China [2]Guangdong Provincial Key Laboratory of Liver Disease Research,Sun Yat-sen University,Guangzhou,510630,Guangdong,China [3]Department of Obstetrics and Gynecology,Women and Children's Hospital of Chongqing Medical University,No.120 Longshan Road,Yubei District,Chongqing,401147,China [4]Department of Obstetrics and Gynecology,Chongqing Health Center for Women and Children,No.120 Longshan Road,Yubei District,Chongqing,401147,China

出　　处：《Bioactive Materials》2024年第11期611-626,共16页生物活性材料（英文）

基　　金：National Key Research and Development Program of China(2019YFA0111300);Thousand Talents Plan,the Guangdong Provincial Pearl River Talents Program(2019QN01Y131);Medical Science and Technology Research Fund of Guangdong Province(A2022112).

摘　　要：The specific induction of hepatic differentiation presents a significant challenge in developing alternative liver cell sources and viable strategies for clinical therapy of acute liver failure (ALF). The past decade has witnessed the blossom of microRNAs in regenerative medicine. Herein, microRNA 122-functionalized tetrahedral framework nucleic acid (FNA-miR-122) has emerged as an unprecedented and potential platform for directing the hepatic differentiation of adipose-derived mesenchymal stem cells (ADMSCs), which offers a straightforward and cost-effective method for generating functional hepatocyte-like cells (FNA-miR-122-iHep). Additionally, we have successfully established a liver organoid synthesis strategy by optimizing the co-culture of FNA-miR-122-iHep with endothelial cells (HUVECs), resulting in functional Hep:HUE-liver spheroids. Transcriptome analysis not only uncovered the potential molecular mechanisms through which miR-122 influences hepatic differentiation in ADMSCs, but also clarified that Hep:HUE-liver spheroids could further facilitate hepatocyte maturation and improved tissue-specific functions, which may provide new hints to be used to develop a hepatic organoid platform. Notably, compared to transplanted ADMSCs and Hep-liver spheroid, respectively, both FNA-miR-122-iHep-based single cell therapy and Hep:HUE-liver spheroid-based therapy showed high efficacy in treating ALF in vivo. Collectively, this research establishes a robust system using microRNA to induce ADMSCs into functional hepatocyte-like cells and to generate hepatic organoids in vitro, promising a highly efficient therapeutic approach for ALF.

关 键 词：Hepatic differentiation Framework nucleic acid Functional hepatic spheroids Transcriptome sequencing analysis Acute liver failure therapy 

分 类 号：R575.3[医药卫生—消化系统]