Stem cell factor as a biomarker in liver allograft rejection and tolerance

Shigeru Goto¹, Toshiaki Nakano¹, Liwen Hsu¹, Kuang-Den Chen¹, Chia-Yun Lai¹, Yu-Fan Cheng¹, Chao-Long Chen¹.

¹Center for Translational Research in Biomedical Sciences, Liver Transplantation Program and Departments of Surgery and Diagnostic Radiology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan.

Liver transplantation is immunologically unique since some patients do not require immunosuppressive drugs after surgery. However, there are no specific biomarkers to determine the timing when immunosuppressive therapy should be reduced or terminated although others and we have reported a substantial number of proteins as candidates of biomarkers for liver allograft tolerance. Most of such proteins can be detected in several weeks after the cessation of immunosuppressive drugs, suggesting that these proteins cannot show the exact timing of withdrawal of immunosuppressive drugs. Therefore, we have currently paid much attention to find out the proteins which appear during rejection.

In the present study, The protein profiles were analyzed in the following three rat models of orthotopic liver transplantation (OLT). 1. OLT (DA-PVG); natural tolerance model, which spontaneously accept donor DA liver without immunosuppressive treatments. 2. OLT (DA-LEW); acute rejection model, which usually reject donor DA liver within 14 days. 3.Drug-induced tolerance model OLT (DA-LEW) with short-term treatment with calcineurin inhibitor cyclosporine. We have found the induction of low molecular proteins (<26 kDa) during rejection phase both in DA-PVG and DA-LEW OLT models. At the time of writing, one of these proteins include stem cell factor (SCF) which increased during rejection phase after liver transplantation in OLT (DA-LEW) and OLT (DA-PVG), gradually decreased in the induction phase of tolerance (after overcome rejection) and then increased again in the maintenance of tolerance in OLT (DA-PVG). SCF is associated with regenerative and immunological characterization of BDSCs or ADSCs of tolerogeneic and rejector OLT. We are now extending our proteomic study in not only post-transplant serum but also in the supernatant of antigen presenting cells or bone marrow derived stem cells (BDSCs) or adipose derived stem cells (ADSCs) of liver-transplant rats.

In conclusion, post-transplant monitoring of SCF may play an important role on prediction of rejection and its therapy to suppress rejection reaction and finally induce tolerance.