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

Nature Medicine volume 10, pages 749–753 (2004)Cite this article

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.

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Figure 1: Histological analysis of auxiliary liver.
Figure 2: Ki-67 immunostaining of liver.
Figure 3: Revascularization of transplanted tissue after 12 d.
Figure 4: 99mTc-mebrofenin handling in transplanted liver.
Figure 5: Function of auxiliary liver in NAR.

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Acknowledgements

We thank C. Zhang for technical assistance. This work was supported in part by NIH grants R01 DK46952 and P30-DK-41296 and by grant G-362 from the International Scientific Technology Center, Moscow, Russia.

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Author notes

  1. Brigid Joseph and Ekaterine Berishvili: These authors contributed equally to this work.

Authors and Affiliations

  1. Marion Bessin Liver Research Center, Bronx, 10461, New York, USA

    Brigid Joseph, Daniel Benten, Vinay Kumaran & Sanjeev Gupta

  2. Department of Medicine, Albert Einstein College of Medicine, Bronx, 10461, New York, USA

    Brigid Joseph, Daniel Benten, Vinay Kumaran & Sanjeev Gupta

  3. Department of Clinical Anatomy and Operative Surgery, Georgian State Medical Academy, Tbilisi, 380079, Georgia

    Ekaterine Berishvili, Ekaterine Liponava & Zurab Kakabadze

  4. Department of Pathology, Albert Einstein College of Medicine, Bronx, 10461, New York, USA

    Sanjeev Gupta

  5. Division of Nuclear Medicine, Radiology Department, Long Island Jewish Medical Center, New York, 11040, USA

    Kuldeep Bhargava & Christopher Palestro

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Correspondence to Sanjeev Gupta.

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Joseph, B., Berishvili, E., Benten, D. et al. Isolated small intestinal segments support auxiliary livers with maintenance of hepatic functions. Nat Med 10, 749–753 (2004). https://doi.org/10.1038/nm1057

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