Lack of evidence of sustained hematopoietic reconstitution after transplantation of unmanipulated adult liver stem cells in monkeys

Abstract

The aim of this study was to search for hematopoietic potential in the liver of non-human primates. Lethally irradiated (2×5 Gy γ) Cynomolgus macaques were given autologous hepatic mononuclear cells (HMNC) isolated from a liver lobe by perfusion and digestion with 0.1% collagenase. Two monkeys were given intramedullary injections of HMNC (18.6×106/kg, 20.4×106/kg) and two others were co-transplanted with HMNC (14.35×106/kg, 96.5×106/kg) and bone marrow mesenchymal stem cells (0.42×106/kg, 1.16×106/kg). All monkeys exhibited a transient neutrophil recovery from day 22 for 10 days, but failed to produce platelets and remained transfusion-dependent. In conclusion, adult liver stem cells from a monkey model show a low level of in vivo hematopoietic potential, suggesting ex vivo manipulation will be required before clinical use of such cells.