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Successful Allotransplantation of Encapsulated Islets in Pancreatectomized Canines for Diabetic Management Without the Use of Immunosuppression

Wang, Taylor1,5; Adcock, Jamie2; Kühtreiber, Willem3; Qiang, Deng1; Salleng, Kenneth J.4; Trenary, Irina1; Williams, Phil2

doi: 10.1097/TP.0b013e3181629c25
Original Articles: Cell Therapy and Islet Transplantation

Background. Pancreatic islet transplantation has shown great success in the treatment of diabetic patients. However, the required immunosuppressive therapy exposes patients to serious side effects.

Methods. We have designed a novel five-component/three-membrane capsule and encapsulation system to protect the transplanted islet cells from immune system attack while allowing the influx of molecules and nutrients necessary for cell function/survival and efflux of the desired cellular product, specifically insulin, for making recipients healthy.

Results. We transplanted encapsulated canine pancreatic islets into the peritoneal cavity of pancreatectomized canines. Transplantation normalized fasting blood glucose levels in nine out of nine dogs for up to 214 days with a single transplantation. Retransplantation was assessed in three animals and encapsulated islets were effective in providing fasting glycemic control after the initial transplantation had run its course. No immunosuppression or anti-inflammatory therapy was used.

Conclusion. This advancement in transplantation may lead to an alternative approach for islet transplantation treatment for diabetic patients. This approach may also benefit patients suffering from other hormone deficiency diseases including liver disease and Parkinson’s disease.

1 Applied Physics Program, Vanderbilt University School of Engineering, Nashville, TN.

2 Department of Surgical Sciences, Vanderbilt University School of Medicine, Nashville, TN.

3 Department of Diabetes, Endocrinology and Metabolism, City of Hope, Duarte, CA.

4 Division of Animal Care, Vanderbilt University School of Medicine, Nashville, TN.

This study was supported by grants from the National Aeronautics and Space Administration (Immunoisolation of Living Islets as a Function Cure for Diabetes), the Juvenile Diabetes Research Foundation (Optimization Studies of PMCG Capsules Toward a Functional Cure for Diabetes), the Evans-Gilruth Foundation, Children’s Miracle Foundation, Ronald McDonald Children’s Charities, and the Vanderbilt Diabetes Research and Training Center (NIH DK20593).

5 Address correspondence to: Taylor Wang, Ph.D., Applied Physics Program, Vanderbilt University School of Engineering, Nashville, TN 37235.

E-mail: taylor.g.wang@vanderbilt.edu

Received 18 June 2007. Revision requested 5 July 2007.

Accepted 9 November 2007.

© 2008 Lippincott Williams & Wilkins, Inc.