The host bone marrow stem cell repopulation is crucial to the permanent tolerance in 50% liver transplantation

Abstract The severe toxicities and side-effects derived from lifelong anti-rejection therapy following organ transplantation necessitates operational tolerance, a immunosuppression-free state in which the allograft functions well and no immunological rejections occur, no operational tolerance is in use globally. Here we introduce that operational tolerance, based on the hypertrophy to hyperplasia transition upon liver regeneration, is early acquired and permanently maintained in 50% adult rat liver allograft transplantation through the host bone marrow stem cell repopulation and 9-day cyclosporine A use. Compared with whole and partial liver transplantations as the controls, longer-term survivals (over 500 days) were observed in the tolerant hosts (p=0.001), the allograft functioned well and no acute or chronic rejections were confirmed by histology examinations. Further study revealed that the allograft was reinstituted by host-derived stem cells marked with CD34, which migrated, repopulated and differentiated after mobilization. However donor-specific hypo-response was not achieved through skin transplantation, indicating no adaptive immune activity occurrence. Our protocol is characteristic of targeting the allograft and non-immunological intervention, offering a novel avenue to operational tolerance induction which is of highly clinical relevance