Entry and integration of transplanted hepatocytes in rat liver plates occur by disruption of hepatic sinusoidal endothelium

Sanjeev Gupta, Pankaj Rajvanshi, Rana Sokhi, Sanjeev Slehria, Ana Yam, Andrew Kerr, Phyllis M. Novikoff

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Abstract

To establish the process by which transplanted cells integrate into the liver parenchyma, we used dipeptidyl peptidase IV-deficient F344 rats as hosts. On intrasplenic injection, transplanted hepatocytes immediately entered liver sinusoids, along with attenuation of portal vein radicles on angiography. However, a large fraction of transplanted cells (>70%) was rapidly cleared from portal spaces by phagocyte/macrophage responses. On the other hand, transplanted hepatocytes entering the hepatic sinusoids showed superior survival. These cells translocated from sinusoids into liver plates between 16 and 20 hours after transplantation, during which electron microscopy showed disruption of the sinusoidal endothelium. Interestingly, production of vascular endothelial growth factor was observed in hepatocytes before endothelial disruptions. Portal hypertension and angiographic changes resulting from cell transplantation resolved promptly. Integration of transplanted hepatocytes in the liver parenchyma required cell membrane regenesis, with hybrid gap junctions and bile canaliculi forming over 3 to 7 days after cell transplantation. We propose that strategies to deposit cells into distal hepatic sinusoids, to disrupt sinusoidal endothelium for facilitating cell entry into liver plates, and to accelerate cell integrations into liver parenchyma will advance applications of hepatocyte transplantation.

Original languageEnglish (US)
Pages (from-to)509-519
Number of pages11
JournalHepatology
Volume29
Issue number2
DOIs
StatePublished - 1999

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Endothelium
Hepatocytes
Liver
Cell Transplantation
Transplantation
Bile Canaliculi
Dipeptidyl Peptidase 4
Gap Junctions
Inbred F344 Rats
Portal Hypertension
Phagocytes
Portal Vein
Vascular Endothelial Growth Factor A
Electron Microscopy
Angiography
Macrophages
Cell Membrane
Injections

ASJC Scopus subject areas

  • Hepatology

Cite this

Entry and integration of transplanted hepatocytes in rat liver plates occur by disruption of hepatic sinusoidal endothelium. / Gupta, Sanjeev; Rajvanshi, Pankaj; Sokhi, Rana; Slehria, Sanjeev; Yam, Ana; Kerr, Andrew; Novikoff, Phyllis M.

In: Hepatology, Vol. 29, No. 2, 1999, p. 509-519.

Research output: Contribution to journalArticle

Gupta, Sanjeev ; Rajvanshi, Pankaj ; Sokhi, Rana ; Slehria, Sanjeev ; Yam, Ana ; Kerr, Andrew ; Novikoff, Phyllis M. / Entry and integration of transplanted hepatocytes in rat liver plates occur by disruption of hepatic sinusoidal endothelium. In: Hepatology. 1999 ; Vol. 29, No. 2. pp. 509-519.
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AU - Yam, Ana

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