Intrasplenic Transplantation of Hepatocytes After Partial Hepatectomy in NOD.SCID Mice

Abstract

Partial hepatectomy is a versatile and reproducible method to study liver regeneration and the effect of cell based therapeutics in various pathological conditions. Partial hepatectomy also facilitates the increased engraftment and proliferation of transplanted cells by accelerating neovascularization and cell migration towards the liver. Here, we describe a simple protocol for performing 30% hepatectomy and transplantation of cells in the spleen of a non-obese diabetic/severe combined immunodeficient NOD.SCID (NOD.CB17-Prkdc/J) mouse. In this procedure, two small incisions are made. The first incision is to expose and resect the left lobe of the liver, and another small incision is made to expose the spleen for the intrasplenic transplantation of cells. This procedure does not require any specialized surgical skills, and it can be completed in 5-7 minutes with less stress and pain, faster recovery, and better survival. We have demonstrated the transplantation of hepatocytes isolated from a green fluorescent protein (GFP) expressing mouse (Transgenic C57BL/6-Tg (UBC-GFP) 30Scha/J), as well as hepatocyte like cells of human origin (NeoHep) in partially hepatectomized NOD.SCID mice.

Domino hepatocyte transplantation using explanted human livers with metabolic defects attenuates D-GalN/LPS-induced acute liver failure

“…To establish a mouse model of ALF, NOD/SCID mice were simultaneously given an intraperitoneal injection of D-GalN (700 mg/kg, Sigma–Aldrich, USA) and LPS (5 μg/kg, Sigma–Aldrich, USA). 6 h after D-GalN/LPS injection, mice were anesthetized using sodium pentobarbital and hepatocytes (2.0 × 10 6 ) isolated from explanted livers with PA or MMA were administered via spleen [ 14 ]. Blood and liver tissues were harvested at 6 h after the hepatocyte administration for evaluation of liver injury (n = 6 in each group; Fig.…”