Stem cell research & therapy · 2025
PD-L1 and ICAM1 over expression empowers immunoregulation of mesenchymal stromal cells to improve the autoimmune hepatitis treatment efficacy.
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Bai Xilong, Liu Tingting, Li Congge, Qiu Caie, Ge Xiaofan, Gou Huili, Cai Hongzhi, Yang Liting, Wei Sili, Yang Wei, Li Tianqing
Аннотация
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: PI-MSCs preserved MSCs identity, with a normal karyotype, stable genome, and no tumorigenicity. The long-term safe dose was up to 5.0 × 107 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.
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: PI-MSCs preserved MSCs identity, with a normal karyotype, stable genome, and no tumorigenicity. The long-term safe dose was up to 5.0 × 107 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.