Work

PD-L1 and ICAM1 over expression empowers immunoregulation of mesenchymal stromal cells to improve the autoimmune hepatitis treatment efficacy

Year: 2025

Type: article

Abstract: BACKGROUND: Autoimmune hepatitis (AIH) is an immune-mediated disease for which there is no effective treatment. Mesenchymal stromal cells (MSCs) have become a promising treatment, but low AIH treatment efficacy has hampered the clinical application of MSCs. METHODS: By using Good Manufacturing Practices, we generated mesenchymal stromal cells with enhanced immunomodulation by over-expressing PD-L1 and ICAM1 (PI-MSCs). PI-MSCs biological characteristics were established, a tertiary cell bank created, and safety of PI-MSCs determined. Finally, the efficacy of PI-MSCs for treatment of AIH was evaluated. RESULTS: cells/kg. PI-MSCs showed better therapeutic effect than conventional MSCs for treating AIH in a mouse model. Notably, PI-MSCs showed better homing to injured liver tissue than conventional MSCs. Furthermore, PI-MSCs treatment significantly increased Treg cells in the blood and spleen of AIH model mice compared to conventional MSCs. CONCLUSION: PD-L1 and ICAM1 empower MSCs immuno-regulation, these empowered MSCs are more effective treatment for AIH. These findings provide support for the translation of PI-MSCs to the clinic for treatment of AIH patients.

Source: Stem Cell Research & Therapy

DOI: 10.1186/s13287-025-04347-w