Introduction: Wilson’s disease is an autosomal recessive genetically inherited disorder of copper metabolism, causing neurological, psychiatric and liver disorders. Cirrhosis due to Wilson’s disease is the end stage of liver disease where transplantation can be the only cure. Many studies encourage use of allogeneic bone marrow (BM) derived mesenchymal stem cells (MSC) for genetic liver diseases. Mesenchymal stem cells (MSCs) are shown to differentiate to hepatocytes. Many experimental and a few clinical trials encourage the use of bone marrow derived allogeneic MSCs in human genetic liver diseases. Here we aimed to assess the differentiation capacities of MSCs to hepatocytes, the changes in regeneration and fibrosis rates in liver tissue before and after MSC transplantation.

Materials and Methods: Study was approved by Ministry of Health Ethical Committee and sponsored by TUBITAK. 6 male, 4 female patients with liver cirrhosis due to Wilson’s disease were recruited (mean age: 33.3). Bone marrows were collected from healthy sex mismatch volunteer donors and sent to Acıbadem Labcell© İstanbul for MSC expansion under GMP (Good Manufacturing Practice) circumstances. Patients were transplanted 1x106 cells/kg, fifty million MSCs via hepatic artery, and the rest via peripheral vein. Patients did not receive any immunosuppressant regimes. Liver biopsies were performed before and 6 months after MSC transplantation. Histopathologic examinations were performed; liver tissue copper amounts were assessed. Also sex mismatch cells were tracked by FISH (fluorescent in situ hybridization) method in biopsy samples. Serum and 24 hour urine copper, serum seruloplasmin levels, biochemical and hematologic parameters were monthly monitored for one year. Periodic USG and MR screenings were obtained.

Results: No side effects due to allogeneic MSC transplantation were seen in neither acute nor chronic post-transplant periods and the procedure was very well tolerated by the patients. When compared with before transplantation, there was no significant change in patients’ liver histopathologic scores and laboratory values. FISH analysis revealed female cells in 5 male patients’ post-transplant 6th month liver biopsy specimens. Transplanted cells which belong to opposite sex donors’ were absent in 4 female and 1 male patients’ control biopsy specimens.

Conclusions: By this study, for the first time in literature bone marrow derived allogeneic MSCs which were transplanted via hepatic artery were shown to differentiate to liver tissue cells. MSC transplantation seems to be a good alternative candidate for liver transplantation in near future.