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Background <p>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.</p> Methods <p>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.</p> Results <p>PI-MSCs preserved MSCs identity, with a normal karyotype, stable genome, and no tumorigenicity. The long-term safe dose was up to 5.0 × 10<sup>7</sup> 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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月24日

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  • Xilong Bai,
  • Tingting Liu,
  • Congge Li,
  • Caie Qiu,
  • Xiaofan Ge,
  • Huili Gou,
  • Hongzhi Cai,
  • Liting Yang,
  • Sili Wei,
  • Wei Yang,
  • Tianqing Li

摘要

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.