title: Isolated small intestinal segments support auxiliary livers with maintenance of hepatic functions.
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.
authors.affiliation: Marion Bessin Liver Research Center, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Brigid
authors.initials: B
authors.lastname: Joseph
authors.forename: Ekaterine
authors.initials: E
authors.lastname: Berishvili
authors.forename: Daniel
authors.initials: D
authors.lastname: Benten
authors.forename: Vinay
authors.initials: V
authors.lastname: Kumaran
authors.forename: Ekaterine
authors.initials: E
authors.lastname: Liponava
authors.forename: Kuldeep
authors.initials: K
authors.lastname: Bhargava
authors.forename: Christopher
authors.initials: C
authors.lastname: Palestro
authors.forename: Zurab
authors.initials: Z
authors.lastname: Kakabadze
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000818:Animals; D002450:Cell Communication; D018819:Dipeptidyl Peptidase 4 / Q000032:analysis; D005786:Gene Expression Regulation; D007421:Intestine, Small / Q000098:blood supply / Q000502:physiology*; D008099:Liver / Q000502:physiology*; D016031:Liver Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D020318:Rats, Long-Evans
chemical_list: D018819:Dipeptidyl Peptidase 4