Genetically and chemically engineered mesenchymal stem cells for liver fibrosis treatment

Mesenchymal stem cells (MSCs) are identified as promising candidates for reversing liver fibrosis benefiting from their excellent properties in tissue repair and immune regulation, while their therapeutic efficacy still requires improvement. Herein, we develop novel multiple engineered MSCs with precise targeting capability and highly expressed growth factors by integrating membrane modification and genetic engineering technology for effective liver fibrosis treatment. These MSCs are imparted with liver-targeting ability via coating their membranes with heparin-lipid conjugates. By utilizing genetic engineering technology to input two designed circular RNA formulations, the MSCs were also imparted with significantly enhanced expression levels and duration of antifibrotic growth factors. Through mouse models of liver fibrosis, we have demonstrated that a single dose of the resultant engineered MSCs can restore liver function by regulating the expression of relevant genes and degrading the extracellular matrix. These promising therapeutic outcomes highlight the significant potential of the engineered MSCs in alleviating liver fibrosis.