Long-Term Graft Function of Adult Rat and Human Islets Encapsulated in Novel Alginate-Based Microcapsules After Transplantation in Immunocompetent Diabetic Mice
- Stephan Schneider1,
- Peter J. Feilen1,
- Frank Brunnenmeier2,
- Timo Minnemann1,
- Heiko Zimmermann3,
- Ulrich Zimmermann2 and
- Matthias M. Weber1
- 1Division of Endocrinology and Metabolism, Medical Department I, University of Mainz, Germany
- 2Department of Biotechnology, Biozentrum, University of Würzburg, Germany
- 3Department of Cryobiophysics and Cryotechnology, Fraunhofer Institute for Biomedical Technique, St. Ingbert, Germany
- Address correspondence and reprint requests to Dr. Stephan Schneider, Medical Department I, University Hospital Bergmannsheil, University of Bochum, Bürkle de la Camp Platz 1, 44789 Bochum, Germany. E-mail: stephan.schneider{at}ruhr-uni-bochum.de
Abstract
We describe the results of the first study to show that adult rat and human islets can be protected against xenogenic rejection in immunocompetent diabetic mice by encapsulating them in a novel alginate-based microcapsule system with no additional permselective membrane. Nonencapsulated islets lost function within 4–8 days after being transplanted into diabetic Balb/c mice, whereas transplanted encapsulated adult rat or human islets resulted in normoglycemia for >7 months. When rat islet grafts were removed 10 and 36 weeks after transplantation, the mice became immediately hyperglycemic, thus demonstrating the efficacy of the encapsulated islets. The explanted capsules showed only a mild cellular reaction on their surface and a viability of >85%, and responded to a glucose stimulus with a 10-fold increase in insulin secretion. Furthermore, transplanted mice showed a slight decrease in the glucose clearance rate in response to intraperitoneal glucose tolerance tests 3–16 weeks after transplantation; after 16 weeks, the rate remained stable. Similar results were obtained for encapsulated human islets. Thus we provide the first evidence of successful transplantation of microencapsulated human islets. In conclusion, we have developed a novel microcapsule system that enables survival and function of adult rat and human islets in immunocompetent mice without immunosuppression for >7 months.
- HBSS, Hank’s balanced salt solution
- HSA, human serum albumin
- IPGTT, intraperitoneal glucose tolerance test
- NPCC, neonatal pancreatic cell cluster
- UW, University of Wisconsin
Footnotes
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- Accepted November 12, 2004.
- Received April 3, 2004.
- DIABETES
