Severe preservation injury induces II-6/STAT3 activation with lack of cell cycle progression after partial liver graft transplantation

Fotini Debonera, Guodong Wang, Jinfu Xie, Xingye Que, Andrew Gelman, Cynthia LeClair, Dong Xin, Abraham Shaked, Kim M. Olthoff

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Partial liver graft transplantation is a surgical advance developed to overcome severe donor shortage. Survival of these grafts involves recovery from cold ischemia and reperfusion (CIR) injury, immediate regeneration and maintenance of function. Here we examined the outcome of partial liver grafts in comparison to whole grafts following CIR injury. Lewis rats subjected to orthotopic liver transplantation (OLT) with whole grafts preserved in Viaspan® were compared to rats receiving 50% and 30% grafts. Outcome was analyzed by survival and regeneration. Transplantation was associated with 100% survival for all grafts, whereas 16 h preservation resulted in 100%, 20% and 0% survival in animals receiving whole, 50% and 30% grafts, respectively. CIR induced increased IL-6 levels in 50% and 30% grafts, and activation of STAT3. Cell cycle progression (cyclin D1) and regeneration (BrdU) was initiated in all livers preserved for 1 or 8 h, but not in partial grafts preserved for 16 h. In conclusion, partial grafts recover from CIR injury through similar molecular pathways to whole grafts. Partial grafts with severe injury fail to achieve cellular proliferation despite the early initiating signals. This failure could be attributed to the impaired ability of the parenchyma to respond to initiating signals for regeneration.

Original languageEnglish
Pages (from-to)1964-1971
Number of pages8
JournalAmerican Journal of Transplantation
Volume4
Issue number12
DOIs
StatePublished - Dec 2004

Keywords

  • IL-6
  • Ischemia and reperfusion injury
  • Liver regeneration
  • Partial liver grafts

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