Isolated small intestinal segments support auxiliary livers with maintenance of hepatic functions.
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.
Joseph
Brigid
B
Marion Bessin Liver Research Center, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Berishvili
Ekaterine
E
Benten
Daniel
D
Kumaran
Vinay
V
Liponava
Ekaterine
E
Bhargava
Kuldeep
K
Palestro
Christopher
C
Kakabadze
Zurab
Z
Gupta
Sanjeev
S
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
D018819:Dipeptidyl Peptidase 4