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Related Experiment Video

Updated: Mar 19, 2026

A Modified Heterotopic Swine Hind Limb Transplant Model for Translational Vascularized Composite Allotransplantation VCA Research
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Development of the Intestinal Transplantation Model With Major Histocompatibility Complex Inbred CLAWN Miniature

K Miura1, H Sahara2, S Waki2

  • 1Division of Organ Replacement and Xenotransplantation Surgery, Kagoshima University, Kagoshima, Japan; Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Transplantation Proceedings
|June 21, 2016
PubMed
Summary

This study established a clinically relevant orthotopic intestinal transplantation (Int-Tx) model in swine. The orthotopic model demonstrated improved graft survival and reduced ischemia compared to heterotopic models, aiding Int-Tx treatment strategies.

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Area of Science:

  • Transplantation immunology
  • Surgical innovation
  • Gastroenterology

Background:

  • Clinical intestinal transplantation (Int-Tx) faces challenges including rejection, infection, graft-versus-host disease, and ischemia-reperfusion injury (IRI).
  • Developing effective Int-Tx treatment strategies requires robust preclinical models.

Purpose of the Study:

  • To establish both heterotopic and orthotopic Int-Tx models in major histocompatibility antigen complex (MHC) inbred CLAWN miniature swine.
  • To evaluate the viability and outcomes of these models for studying Int-Tx mechanisms and treatments.

Main Methods:

  • Eleven MHC-matched but minor antigen-mismatched allogeneic intestinal grafts were performed in CLAWN miniature swine.
  • Four grafts were heterotopic (host intestine intact), and seven were orthotopic (host small intestine resected).
  • Tacrolimus was administered continuously for 12 days post-transplantation.

Main Results:

  • Heterotopic grafts experienced ischemic changes due to abdominal space limitations.
  • Orthotopic grafts showed no signs of severe ischemia; recipients had reduced inflammatory cytokines and acidosis.
  • Two orthotopic recipients survived over 30 days, with one long-term survivor showing no rejection at 90 days despite cessation of immunosuppression.

Conclusions:

  • A clinically relevant orthotopic Int-Tx model with long survival was successfully established in MHC-inbred CLAWN miniature swine.
  • This swine model provides a valuable platform for developing and testing novel treatment strategies for clinical Int-Tx.