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<p>Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is associated with a high mortality rate. Although mesenchymal stem cell (MSC) therapy markedly improves liver function and survival in patients with HBV-ACLF, it remains unclear whether the immunomodulatory effects of MSCs suppress antiviral CD8⁺ T cell function and trigger HBV reactivation. Here, we developed a novel in vitro HBV-specific CD8⁺ T cell–mediated acute liver injury organoid model, which was co-cultured with either menstrual blood-derived MSCs (MenSCs) or umbilical cord-derived MSCs (UC-MSCs). We found that both MenSCs and UC-MSCs coordinate liver repair and antiviral immunity through precise immunomodulation, primarily via paracrine signaling. Both MSC types significantly downregulated pro-inflammatory (<i>IFN-γ</i>,<i> TNF-α</i>,<i> IL-8</i>,<i> and CXCL10</i>) and apoptosis-related genes (<i>FasL</i> and <i>CASP7</i>), while promoting hepatic regeneration through <i>IL-6</i> and <i>HGF</i> upregulation, without compromising CD8⁺ T cell-mediated HBV clearance. This study provides critical insights into the safety of MSC therapy for HBV-ACLF.</p>

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Precise immunomodulation by mesenchymal stem cells mitigates hepatitis B virus-specific CD8⁺ T cell-mediated acute liver injury without compromising viral clearance

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月27日

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  • Xingxing Li,
  • Zhiwei Li,
  • Qibin Liao,
  • Yanhong Huang,
  • Shumin Liao,
  • Liang Li

摘要

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is associated with a high mortality rate. Although mesenchymal stem cell (MSC) therapy markedly improves liver function and survival in patients with HBV-ACLF, it remains unclear whether the immunomodulatory effects of MSCs suppress antiviral CD8⁺ T cell function and trigger HBV reactivation. Here, we developed a novel in vitro HBV-specific CD8⁺ T cell–mediated acute liver injury organoid model, which was co-cultured with either menstrual blood-derived MSCs (MenSCs) or umbilical cord-derived MSCs (UC-MSCs). We found that both MenSCs and UC-MSCs coordinate liver repair and antiviral immunity through precise immunomodulation, primarily via paracrine signaling. Both MSC types significantly downregulated pro-inflammatory (IFN-γ, TNF-α, IL-8, and CXCL10) and apoptosis-related genes (FasL and CASP7), while promoting hepatic regeneration through IL-6 and HGF upregulation, without compromising CD8⁺ T cell-mediated HBV clearance. This study provides critical insights into the safety of MSC therapy for HBV-ACLF.