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Peer-reviewedCC BYStem Cell Research & Therapy

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

  • Xingxing Li1
  • Zhiwei Li2
  • Qibin Liao3
  • Yanhong Huang1
  • Shumin Liao1
  • Liang Li1
  1. 1Department of Pharmacology, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology
  2. 2Department of Hepato-Biliary Surgery, Shenzhen Third People’s Hospital, Second Hospital Affiliated to Southern University of Science and Technology
  3. 3State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{li2026precise,
  title = {{Precise immunomodulation by mesenchymal stem cells mitigates hepatitis B virus-specific CD8⁺ T cell-mediated acute liver injury without compromising viral clearance}},
  author = {Xingxing Li and Zhiwei Li and Qibin Liao and Yanhong Huang and Shumin Liao and Liang Li},
  journal = {Stem Cell Research \& Therapy},
  year = {2026},
  month = jul,
  doi = {10.1186/s13287-026-05105-2},
  url = {https://doi.org/10.1186/s13287-026-05105-2},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Precise immunomodulation by mesenchymal stem cells mitigates hepatitis B virus-specific CD8⁺ T cell-mediated acute liver injury without compromising viral clearance
AU  - Xingxing Li
AU  - Zhiwei Li
AU  - Qibin Liao
AU  - Yanhong Huang
AU  - Shumin Liao
AU  - Liang Li
PY  - 2026
DA  - 2026/07/01
JO  - Stem Cell Research & Therapy
DO  - 10.1186/s13287-026-05105-2
UR  - https://doi.org/10.1186/s13287-026-05105-2
AB  - 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.
SN  - 1757-6512
ER  -