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

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

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-

SUBMITTER: Bai X 

PROVIDER: S-EPMC12023376 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature