Isolated small intestinal segments support auxiliary livers with maintenance of hepatic functions

Brigid Joseph, Ekaterine Berishvili, Daniel Benten, Vinay Kumaran, Ekaterine Liponava, Kuldeep Bhargava, Christopher Palestro, Zurab Kakabadze, Sanjeev Gupta

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

We determine here the functional integrity of auxiliary livers in containers fashioned from the small intestine. Liver microfragments from dipeptidyl peptidase 4 (DPP4)-deficient rats were transplanted into syngeneic normal animals with isolated intestinal segments characterized by mucosal denudation but intact vascular supply. Transplanted liver fragments were restored to confluent tissue with normal hepatic architecture and development of DPP4-positive vessels, indicating angiogenesis and revascularization. Auxiliary liver units expressed multiple hepatotrophic and angiogenic genes, and transplanted tissues remained intact for up to the 6-week duration of the studies with neither ischemic injury nor significant hepatocellular proliferation. Hepatic metabolic, transport and synthetic functions were preserved in auxiliary livers, including uptake and biliary excretion of 99mTc-mebrofenin in syngeneic recipients of liver from F344 rats, as well as secretion of albumin in allografted Nagase analbuminemic rats. This ability to produce functionally competent auxiliary livers in vascularized intestinal segments offers therapeutic potential for liver disease and genetic deficiency.

Original languageEnglish (US)
Pages (from-to)749-753
Number of pages5
JournalNature Medicine
Volume10
Issue number7
DOIs
StatePublished - Jul 1 2004

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Joseph, B., Berishvili, E., Benten, D., Kumaran, V., Liponava, E., Bhargava, K., Palestro, C., Kakabadze, Z., & Gupta, S. (2004). Isolated small intestinal segments support auxiliary livers with maintenance of hepatic functions. Nature Medicine, 10(7), 749-753. https://doi.org/10.1038/nm1057