Nucleic acid spheres for treating capillarisation of liver sinusoidal endothelial cells in liver fibrosis by Wenjia Liu & Yuting Liu & Liqiang Zhang & Liya Li & Wenguang Yang & Jia Li & Wangxiao He instant download

Nucleic acid spheres for treating capillarisation of liver sinusoidal endothelial cells in liver fibrosis by Wenjia Liu & Yuting Liu & Liqiang Zhang & Liya Li & Wenguang Yang & Jia Li & Wangxiao He instant download

Liver sinusoidal endothelial cells (LSECs) lose their characteristic fenestrations1234567890():,;1234567890():,;Check for updatesand become capillarized during the progression of liver fibrosis. Mesenchymalstem cell (MSC) transplantation can reverse this capillarization and reducefibrosis, but MSC therapy has practical limitations that hinder its clinical use.Here, with the help of artificial intelligence (AI), we show that MSCs secrete amicroRNA (miR-325-3p) that helps restore LSEC fenestrations (tiny pores) bymodulating their cytoskeleton, effectively reversing capillarization. We furtherdevelop a spherical nucleic acid (SNA) nanoparticle carrying miR-325-3p as analternative to MSC therapy. This SNA specifically enters fibrotic LSECs via thescavenger receptor A (Scara). In three mouse models of liver fibrosis, the SNAtreatment restores LSEC fenestrations, reverses capillarization, and significantly reduces fibrosis without adverse effects. Our findings highlight thepotential of SNA-based therapy for liver fibrosis, paving the way for targetednucleic acid treatments directed at LSECs and offering hope for patients.