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Title

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

Authors
Joseph, Brigid
Benten, Daniel
Kumaran, Vinay
Liponava, Ekaterine
Bhargava, Kuldeep
Palestro, Christopher
Kakabadze, Zurab
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Published in Nature Medicine. 2004, vol. 10, no. 7, p. 749-753
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 (99m)Tc-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.
Keywords AnimalsCell CommunicationDipeptidyl Peptidase 4/analysisGene Expression RegulationIntestine, Small/blood supply/physiologyLiver/physiologyLiver TransplantationRatsRats, Inbred F344Rats, Long-Evans
Identifiers
PMID: 15170210
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Article (Published version) (1.7 MB) - document accessible for UNIGE members only Limited access to UNIGE
Other version: https://www.nature.com/articles/nm1057
Research group Création de tissus par bio-ingénieurie et régénération d'organes (1021)
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JOSEPH, Brigid et al. Isolated small intestinal segments support auxiliary livers with maintenance of hepatic functions. In: Nature Medicine, 2004, vol. 10, n° 7, p. 749-753. doi: 10.1038/nm1057 https://archive-ouverte.unige.ch/unige:138409

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Deposited on : 2020-07-14

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