Amphiphilic lipid-peptide engineered placenta-derived mesenchymal stem cells for liver fibrosis treatment

Abstract

The global mortality rate due to liver diseases, particularly liver fibrosis, is increasing. Among various treatment methods, stem cell therapy using placenta-derived mesenchymal stem cells (PDMSCs) offers distinct benefits, including ease of isolation and superior proliferative potential. To enhance the therapeutic efficacy of PDMSCs, the WKYMVm peptide was selected for cell engineering. Immobilization of WKYMVm on PDMSC membranes facilitates effective peptide binding to the formyl peptide receptor 2 on adjacent PDMSCs and hepatocytes, thereby enhancing cell activation and achieving more efficient peptide utilization compared to bolus peptide treatment. Increased cell activation enhances the secretion of paracrine factors including growth factors and cytokines, which in turn improves liver function and vascular repair in both in vitro and in vivo models. This approach not only enhances the angiogenic and therapeutic capacities of stem cells, but also enables efficient peptide utilization, minimizing potential side effects and costs associated with high peptide dosages. Overall, our study demonstrates significant promise of stem cell therapy for treating liver fibrosis. Thus, stem cell therapy offers considerable prospects for clinical applications.