Abstract
Liver transplantation (LT) has become the best chance and a routine practice for patients with end-stage liver disease and small hepatocellular carcinoma. However, life-long immunosuppressive regimens could lead to many post-LT complications, including cancer recurrence, infections, dysmetabolic syndrome, and renal injury. Impeccable management of immunosuppressive regimens is indispensable to ensure the best long-term prognosis for LT recipients. This is challenging for these patients, who probably have a post-LT graft survival of more than 10 or even 20 years. Approximately 20% of patients after LT could develop spontaneous operational tolerance. They could maintain normal graft function and histology without any immunosuppressive regimens. Operational tolerance after transplantation has been an attractive and ultimate goal in transplant immunology. The liver, as an immunoregulatory organ, generates an immune hyporesponsive microenvironment under physiological conditions. In this regard, LT recipients may be ideal candidates for studies focusing on operative tolerance. Cell-based strategies are one of the most promising methods for immune tolerance induction, including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory T cells, regulatory dendritic cells, regulatory macrophages, regulatory B cells, and mesenchymal stromal cells. The safety and the efficacy of many cell products have been evaluated by prospective clinical trials. In this review, we will summarize the latest perspectives on the clinical application of cell-based strategies in LT and will address a number of concerns and future directions regarding these cell products.
Highlights
Liver transplantation (LT) has become the best chance for patients with end-stage liver disease and small hepatocellular carcinoma with chronic liver disease since it was first performed in 1963 [1, 2]
20% of recipients could become completely tolerant without any immunosuppressant drugs after LT [5,6,7], whereas such “operational tolerance” is reported only anecdotally in recipients of other organs [8]
We mainly focus on cell-based strategies of tolerance induction in LT by clarifying the translational potential of these strategies
Summary
Liver transplantation (LT) has become the best chance for patients with end-stage liver disease and small hepatocellular carcinoma with chronic liver disease since it was first performed in 1963 [1, 2]. Among highly selected LT recipients, some of them could discontinue all immunosuppression for more than 1 year while maintaining a stable allograft status, which is defined as “operational tolerance” [3, 4]. For these reasons, tolerance of LT has been an attractive and ultimate goal in transplant immunology. Compared to that in other solid organ transplantations, the incidence of chronic rejection in LT is lower [15] With this background, LT recipients may be ideal candidates for clinical trials studying operative tolerance. We mainly focus on cell-based strategies of tolerance induction in LT by clarifying the translational potential of these strategies
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