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Encapsulation of Porcine Islets Permits Extended Culture Time and Insulin Independence in Spontaneously Diabetic BB Rats

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Abstract:

The ability to culture porcine islets for extended times allows for both their functional assessment and the assurance of their microbiological safety prior to transplantation. We have previously shown that agarose-encapsulated porcine islets can be cultured for at least 24 weeks. In the current study, porcine islet agarose macrobeads cultured for up to 67 weeks were assessed for their ability to restore normoglycemia, respond to an intraperitoneal glucose challenge, maintain spontaneously diabetic BB rats free of insulin therapy for more than 6 months, and for their biocompatibility. Porcine islets were encapsulated in agarose macrobeads and subjected to weekly static perifusion assays for the assessment of insulin production. After in vitro culture for either 9, 40, or 67 weeks, 56–60 macrobeads were transplanted to each spontaneously diabetic BB rat. Transplanted rats were monitored daily for blood glucose levels. Glucose tolerance tests and assessments for porcine C-peptide were conducted at various intervals throughout the study. Normoglycemia (100–200 mg/dl) was initially restored in all islet transplanted rats. Moderate hyperglycemia (200–400 mg/dl) developed at around 30 days posttransplantation and continued throughout the study period of 201–202 days. Importantly, all rats that received encapsulated porcine islets continued to gain weight and were free of exogenous insulin therapy for the entire study. Porcine C-peptide (0.2–0.9 ng/ml) was detected in the serum of islet recipients throughout the study period. No differences were detected between recipient animals receiving islet macrobeads of various ages. These results demonstrate that the encapsulation of porcine islets in agarose macrobeads allows for extended culture periods and is an appropriate strategy for functional and microbiological assessment prior to clinical use.

Keywords: Encapsulation; Islet culture; Porcine islets; Xenotransplantation

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/000000007783465028

Affiliations: 1: The Rogosin Institute-Xenia Division, Xenia, OH 45385, USA, The Rogosin Institute, New York, NY 10021, USA 2: The Rogosin Institute-Xenia Division, Xenia, OH 45385, USA 3: The Rogosin Institute, New York, NY 10021, USA, New York-Presbyterian Hospital and Weill Medical College of Cornell University, New York, NY 10021, USA 4: The Rogosin Institute-Xenia Division, Xenia, OH 45385, USA, Bob Evans Farms, Inc., Columbus, OH 43207, USA 5: The Rogosin Institute-Xenia Division, Xenia, OH 45385, USA, The Rogosin Institute, New York, NY 10021, USA, New York-Presbyterian Hospital and Weill Medical College of Cornell University, New York, NY 10021, USA

Publication date: June 1, 2007

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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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