Extracellular matrix component cotransplantation prolongs survival of heterotopically transplanted human hepatocytes in mice

Heterotopically Transplanted Hepatocyte Survival Depends on Extracellular Matrix Components

“…In our previous reports, significantly higher hepatocyte survival was achieved when human or mouse hepatocytes were cotransplanted with EHS-ECMs at heterotopic sites as compared to hepatocytes without ECMs. 1,4,5 In line with these data, significantly higher and sustained survivals were achieved in group 2 (hepatocytes with EHS-ECMs) compared with the survival of hepatocytes alone (group 1). When hepatocytes were transplanted with growth factor-reduced EHS-ECMs (group 3), sustained survival was also achieved with no difference in survival compared to group 2.…”

“…Since the marker protein of the transplanted hepatocytes, hAAT, demonstrates a short half-life (less than 2 hours) in the mouse 7 and is produced only from the hepatocytes, the viability and survival of the transplanted hepatocytes in vivo can reasonably be assessed by periodic mouse serum measurement of the hAAT reporter protein, as described previously. [3][4][5][6][7] Mice were sacrificed at day 140; the grafts were excised and processed for histological examination.…”

“…1,2 We recently reported that the inefficient hepatocyte survival may be overcome by providing ECMs extracted from murine Engelbreth-Holm-Swarm tumor cell lines (EHS-ECMs). [3][4][5][6] The EHS-ECMs are rich in ECM components, predominantly laminin and type IV collagen, but also contain a small amount of growth factors, such as epidermal growth factor. This study was performed to determine the effects of EHS-ECMs on hepatocyte survival and whether it was solely due to ECMs or to a combination of ECMs and growth factors in EHS-ECMs.…”

Maintenance of Hepatic Functions in Primary Human Hepatocytes Cultured on Xeno-Free and Chemical Defined Human Recombinant Laminins

“…From hepatocyte transplants point of view, it has demonstrated that human hepatocytes graft transplanted into the mouse subcutaneous space or under the kidney capsule survived significantly longer-period when extracellular matrix components were provided to the grafts [24]. It has been demonstrated that elevated CYP3A4 activity in hepatocytes grown on matrices or encapsulated to create a 3-dimentional environment [25–27].…”

Loss of integrin linked kinase from mouse hepatocytesin vitro andin vivo results in apoptosis and hepatitis

“…Of particular importance for normal hepatocyte function, both in vivo and in vitro, is the surrounding matrix. 1,3,40,41 ILK is a cell-ECM adhesion protein that mediates signal transduction between integrins, ECM, and the interior of cells. It directly interacts with PINCH and ␣-parvin, and together they form a stable ternary complex at the cell-ECM adhesion sites.…”