Kupffer cells participate in early clearance of syngeneic hepatocytes transplanted in the rat liver

Perturbations in Ataxia Telangiectasia Mutant Signaling Pathways After Drug-Induced Acute Liver Failure and Their Reversal During Rescue of Animals by Cell Therapy

“…In some mice, 2 ϫ 10 6 Rosa26 cells were transplanted simultaneously via the spleen for deposition into the liver, as previously described. 13 Cells were transplanted within 2 hours after isolation. Multiple groups of animals were established, as indicated in individual studies, including control mice treated with vehicle and microcarriers alone.…”

“…Cell transplantation in liver sinusoids may even be undesirable in ALF because occlusion of blood flow by transplanted cells might worsen hepatic injury. [11][12][13][14] Moreover, transplanted hepatocytes integrate in liver parenchyma over several days and take far longer to proliferate, 6,8 casting doubt on the importance of reseeding of the liver in ALF. By contrast, spacious extrahepatic sites (eg, the peritoneal cavity) may accommodate many transplanted cells.…”

Hepatocyte transplantation activates hepatic stellate cells with beneficial modulation of cell engraftment in the rat

“…[1][2][3][4][5] Using DPPIVϪ rats, we demonstrate here that hepatocyte transplantation partially activated HSC, including expression of growth factors and ECM-modifying matrix metalloproteinases (MMPs), which are largely produced in HSC. 7,8 Moreover, depletion of HSC interfered with cell engraftment.…”

Liver gene therapy: advances and hurdles

“…77 Most of the entrapped hepatocytes were destroyed by activated phagocytotic responses. 78 The remaining cells translocated from sinusoids into liver plates within 20 h after cell transplantation, through a process involving disruption of the sinusoidal endothelium, release of vascular endothelial growth factor (VEGF) by both host and transplanted hepatocytes. 77,79,80 Subsequently, translocated cells integrated into the liver parenchyma, regained their polarity with the formation of gap junctions and bile canaliculi between transplanted and host hepatocytes within about 1 week, without any significant proliferation in adult animals and were functional throughout the life of animals.…”

“…Hepatocyte engraftment could also be significantly increased: (i) by increasing the number of donor cells depositing in hepatic sinusoids using vasodilators; (ii) by disrupting the sinusoidal endothelial endothelium using drugs such as cyclosphamide; and (iii) by depleting macrophage/Kuppfer cells prior to hepatocyte transplantation using gadolinium chloride. 78,86,87 Other strategies were aimed at amplifying the hepatic mass of transplanted hepatocytes after they had integrated into the liver parenchyma. Partial hepatectomy and hepatocyte growth factor infusion were ineffective in increasing the transplanted hepatocyte mass, because both transplanted and host hepatocytes had been removed and/or responded equally to the regenerative stimuli.…”