Stem Cell Research & Therapy (Apr 2021)

A novel MSC-based immune induction strategy for ABO-incompatible liver transplantation: a phase I/II randomized, open-label, controlled trial

  • Yingcai Zhang,
  • Jiebin Zhang,
  • Huimin Yi,
  • Jun Zheng,
  • Jianye Cai,
  • Wenjie Chen,
  • Tongyu Lu,
  • Liang Chen,
  • Cong Du,
  • Jianrong Liu,
  • Jia Yao,
  • Hui Zhao,
  • Guoying Wang,
  • Binsheng Fu,
  • Tong Zhang,
  • Jian Zhang,
  • Genshu Wang,
  • Hua Li,
  • Andy Peng Xiang,
  • Guihua Chen,
  • Shuhong Yi,
  • Qi Zhang,
  • Yang Yang

DOI
https://doi.org/10.1186/s13287-021-02246-4
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 15

Abstract

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Abstract Background ABO-incompatible liver transplantation (ABO-i LT) has become a rescue therapeutic option for patients with severe hepatic failure. Although the use of rituximab greatly reduces the morbidity of antibody-mediated rejection (AMR), severe adverse effects, such as infection and biliary complications, still seriously threaten the survival of transplant recipients. The aim of this study was to evaluate the safety and feasibility of using mesenchymal stem cells (MSCs) to replace rituximab in ABO-i LT. Methods Twenty-two patients with severe hepatic failure undergoing ABO-i LT were enrolled and randomly divided into two groups: the MSC group and the rituximab group. The safety of the application of MSCs and the incidence of allograft rejection, including antibody-mediated rejection (AMR) and acute cellular rejection (ACR), were evaluated in both groups at the 2-year follow-up period as primary endpoints. Recipients and graft survival and other postoperative complications were compared as secondary endpoints. Results No severe MSC-related adverse events were observed during the trial. MSC treatment yielded comparable, if not better, results than rituximab at decreasing the incidence of acute rejection (9.1% vs 27.3%). Inspiringly, compared to those in the rituximab group, the rates of biliary complications (0% vs 45.5%) and infection (9.1% vs 81.8%) were significantly decreased in the MSC group. In addition, there were no significant differences in 2-year graft and recipient survival between the two groups (81.8% vs 72.7%). Conclusions Our data show that MSC transfusion is comparable to rituximab treatment for AMR prophylaxis following ABO-i LT. Additionally, the results indicate that MSCs are more beneficial to the prevention of infection and biliary complications and may be introduced as a novel immunosuppressive approach for ABO-i LT. Trial registration Trial registration: chictr.org.cn , ChiCTR2000037732. Registered 31 August 2020- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=57074 .

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