A Simple and Effective Method to Improve Intrasplenic Rat Hepatocyte Transplantation

Abstract

Transplanted hepatocytes integrate, survive, and express their specific functions in the liver parenchyma. The aim of this study was to determine whether a large number of hepatocytes could move from the spleen to the liver when the cells are injected together with sodium nitroprusside, and if the improved hepatocyte migration may be related with portal vein dilatation. Wistar rats were transplanted in the spleen with fluorescent-labeled hepatocytes alone or together with sodium nitroprusside. At 1, 3, 6, and 24 h after the transplant, the liver from recipient animals was removed and morphometric analyses were performed. Portal and arterial pressures were also measured immediately after intrasplenic injection of a solution of sodium nitroprusside, hepatocytes alone, or hepatocytes plus sodium nitroprusside. Intrasplenically injected sodium nitroprusside produced a transient drop in arterial pressure and a sustained reduction in portal pressure. During hepatocyte transplantation it increased the number of transplanted cells migrating to the liver after 3 h. Sodium nitroprusside simultaneously injected with hepatocytes in the spleen allowed more cells to migrate into the liver of the host animal without risk in animal survival.

In vivo imaging of transplanted hepatocytes with a 1.5-T clinical MRI system—initial experience in mice

“…Intrasplenic and intraportal hepatocyte injection [13,14] both lead to hepatocyte integration within the liver parenchymal plates [15]. It is, however, well established that in normal rodent liver the proportion of transplanted hepatocytes which engraft in the liver parenchyma is low, approximately 1% [16].…”

Efficient cold transfection of pea ferredoxin‐NADP(H) oxidoreductase into rat hepatocytes

“…Before transplantation, hepatocytes were labeled with 10 µM CFSE for 15 min at 37 °C under agitation 25. Transplantation was performed through an intrasplenic injection of about 2 × 10 7 hepatocytes at high cellular concentration (5 × 10 7 cell/mL) 5, 23, representing 1–2% of total rat liver hepatocyte mass 3. Animals were sacrificed at different time points after transplantation and livers were harvested for histological examination and transgene expression analysis.…”

“…The last option relies on the observation that about one‐half of the transplanted hepatocytes is either lost or eliminated by the recipient organ and, consequently, would not contribute to functional replacement 4. A number of approaches have been suggested to improve hepatocyte engraftment and/or avoid elimination by the host such as co‐administration of a vasodilator 5 or genetic modification 6.…”

Intrasplenic Preconditioning: A Model for the Study of Xenostimuli Accommodation

“…Indeed, intrasplenic injection has frequently been used as an experimental technique for hepatocyte transplantation [26]. Finally, xenotransplantation studies have used 40-50 mL of human blood, an amount considered adequate to cause xenograft native antibody molecules to be deposited on all endothelial cells.…”