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

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. 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. 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%). 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: chictr.org.cn, ChiCTR2000037732. Registered 31 August 2020- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=57074.

ABO血型不相容肝移植（ABO - i LT）已成为重症肝衰竭患者的一种挽救性治疗选择。尽管利妥昔单抗的使用大大降低了抗体介导的排斥反应（AMR）的发病率，但感染和胆道并发症等严重不良反应仍然严重威胁移植受者的生存。本研究的目的是评估在ABO - i LT中使用间充质干细胞（MSCs）替代利妥昔单抗的安全性和可行性。 22例接受ABO - i LT的重症肝衰竭患者入选，并随机分为两组：间充质干细胞组和利妥昔单抗组。在2年随访期内，将两组间充质干细胞应用的安全性以及同种异体移植排斥反应（包括抗体介导的排斥反应和急性细胞排斥反应）的发生率作为主要终点进行评估。将受者和移植物的存活率以及其他术后并发症作为次要终点进行比较。 试验期间未观察到与间充质干细胞相关的严重不良事件。在降低急性排斥反应发生率方面，间充质干细胞治疗即使不比利妥昔单抗更好，也能取得相当的效果（9.1%对27.3%）。令人鼓舞的是，与利妥昔单抗组相比，间充质干细胞组的胆道并发症发生率（0%对45.5%）和感染率（9.1%对81.8%）显著降低。此外，两组间2年移植物和受者存活率无显著差异（81.8%对72.7%）。 我们的数据表明，在ABO - i LT后预防AMR方面，间充质干细胞输注与利妥昔单抗治疗相当。此外，结果表明间充质干细胞更有利于预防感染和胆道并发症，可作为ABO - i LT的一种新型免疫抑制方法引入。 试验注册：chictr.org.cn，ChiCTR2000037732。2020年8月31日注册 - 回顾性注册，http://www.chictr.org.cn/showproj.aspx?proj=57074