Amphiphilic lipid conjugate-mediated surface engineering of placenta-derived mesenchymal stem cells for alleviating liver damage and fibrosis

Abstract

Stem cell-mediated regenerative medicine is demonstrating remarkable therapeutic efficacy for various diseases, including liver diseases. Placenta-derived mesenchymal stem cells (PDMSCs) are readily obtained without invasive procedures and have exhibited excellent efficacy for liver treatment. Nonetheless, the clinical efficacy of MSCs is frequently hampered by their inadequate migration to damaged tissues and suboptimal engraftment. Herein, lipid-conjugated lactobionic acid (LA-Lipid) was developed to enhance the interaction of PDMSCs with hepatocytes and their engraftment into liver tissue. This biomaterial was designed for (1) lipid-mediated anchoring of the PDMSC membrane and (2) effective presentation of LA, a ligand for the asialoglycoprotein receptor. The LA-Lipid swiftly engineered the surface of PDMSCs within 30 min, resulting in LA-coated PDMSCs (LA-PDMSCs) that exhibited notable physical adhesion to damaged hepatocytes. These hepatocyte-recognizing PDMSCs were active in releasing liver repair agents, mitigating damage to hepatocytes and reducing liver fibrosis. Moreover, in the bile duct ligation rat model, the administered LA-PDMSCs demonstrated significant engraftment into liver tissue, leading to enhanced liver recovery and anti-fibrotic effects compared to unmodified PDMSCs. Overall, the LA-Lipid biomaterials enhance the engraftment and cellular interaction of PDMSCs, thereby facilitating effective treatment of liver injuries and pointing to a promising direction in stem cellmediated regenerative therapies.