TY - JOUR
T1 - Isolated small intestinal segments support auxiliary livers with maintenance of hepatic functions
AU - Joseph, Brigid
AU - Berishvili, Ekaterine
AU - Benten, Daniel
AU - Kumaran, Vinay
AU - Liponava, Ekaterine
AU - Bhargava, Kuldeep
AU - Palestro, Christopher
AU - Kakabadze, Zurab
AU - Gupta, Sanjeev
N1 - Funding Information:
We thank C. Zhang for technical assistance. This work was supported in part by
PY - 2004/7
Y1 - 2004/7
N2 - 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.
AB - 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.
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U2 - 10.1038/nm1057
DO - 10.1038/nm1057
M3 - Article
C2 - 15170210
AN - SCOPUS:3142674188
SN - 1078-8956
VL - 10
SP - 749
EP - 753
JO - Nature Medicine
JF - Nature Medicine
IS - 7
ER -