Availability of bone marrow stromal cells in three-dimensional coculture with hepatocytes and transplantation into liver-damaged mice.

Rat bone marrow stromal cells (BMSCs) were cultured in porous hydroxyapatite (HA) disks for 2 weeks to form a cell layer on the surface. Freshly isolated hepatocytes were then inoculated into both BMSC-cultured and non-treated HA disks. Hepatocytes cocultured with BMSCs secreted significantly more albumin than those in monoculture in vitro. The cell-packed HA disks were implanted into the peritoneal cavity of Nagase analbuminemia rats (NARs), and 4 weeks later, blood samples were collected to measure the albumin concentration. The cotransplantation of BMSCs with hepatocytes significantly increased the serum albumin concentration in NARs. The HA disks coculturing mice hepatocytes and BMSCs were also implanted into mice, in which liver damage had been induced using carbon tetrachloride and phenobarbital. The decreased serum albumin level in liver-damaged mice was completely recovered by the transplantation of hepatocytes and BMSCs. The serum level of IL-6 in liver-damaged mice was also increased by the cotransplantation of BMSCs and hepatocytes. Thus, the transplantation of BMSCs appears to have a systemic effect on recipients through the increase in the serum cytokine level as well as a local effect on cotransplanted hepatocytes.