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Cell Biochemistry and Biophysics

, Volume 48, Issue 2–3, pp 201–207 | Cite as

Vascularized composite islet-kidney transplantation in a miniature swine model

  • Prashanth Vallabhajosyula
  • Adam Griesemer
  • Kazuhiko Yamada
  • David H. SachsEmail author
Original Paper

Abstract

Previous work from this laboratory has demonstrated that transplantation of allogeneic thymic tissue as part of a composite vascularized graft is far more successful in terms of both engraftment and long-term survival than transplantation of thymic tissue or cells alone. We have subsequently extended this concept to transplantation of allogeneic islets, comparing survival of islet cell suspensions to that of vascularized composite islet-kidneys (IK), prepared by injection of autologous islets underneath the renal capsule 2-3 months prior to allogeneic transplantation of the composite organ.

We have utilized partially inbred miniature swine with defined MHC loci as the experimental large animals for this study, permitting reproducible transplantation across specific MHC barriers. Composite IK have been transplanted successfully across minor and full MHC mismatch barriers, using treatment regimens previously demonstrated to induce long-term tolerance of kidney allografts across these barriers. IK allografts containing ≥5000 islet equivalents (IE)/kg recipient body weight were found capable of reversing surgically induced diabetes, while injection of comparable numbers of purified islets via the portal vein or under the renal capsule did not. Studies are also being directed toward preparation of autologous “thymo-islet-kidneys” (TIK), for potential use as xenografts, in which the thymic component is intended to induce tolerance and the islets to reverse diabetic hyperglycemia. The use of both types of composite organ transplants may eventually be applicable to the treatment of type I diabetic patients suffering from end-stage diabetic nephropathy.

Keywords

Islet Transplantation Islet-kidney Swine Thymo-islet-kidney Kidney 

Notes

Acknowledgements

The authors thank Novartis Pharmaceutical Corporation for providing cyclosporin, and Astellas Pharma Inc. for providing tacrolimus. This work was supported by National Institutes of Health Grant 1R33DK069827 and Juvenile Diabetes Research Foundation Grant 1-2004-343. We also thank Dr. Megan Sykes for her helpful review of this manuscript and Ms. Maria Doherty and Ms. Annette Sugrue for secretarial assistance.

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Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Prashanth Vallabhajosyula
    • 1
  • Adam Griesemer
    • 1
  • Kazuhiko Yamada
    • 1
  • David H. Sachs
    • 1
    Email author
  1. 1.Transplantation Biology Research CenterMassachusetts General Hospital and Harvard Medical SchoolBostonUSA

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