Journal
TRANSPLANTATION
Volume 90, Issue 10, Pages 1054-1062Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0b013e3181f6e267
Keywords
Pig islets; Xenotransplantation; Primates; Encapsulation; Diabetes correction
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Funding
- Foundation Louvain, Universite catholique de Louvain
- Fonds de la Recherche Scientifique Medicale, Brussels [3-4503-03]
- Fonds Special de Recherche, Communaute Francaise, Belgium
- European grant [UELSHB-CT-2006-037377]
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Background. This study assessed the capacity of alginate-encapsulated islets to reverse diabetes in a pig-to-primate model. Methods. Adult pig islets were encapsulated in microcapsules implanted under the kidney capsule (n = 4) or in a subcutaneous macrodevice (n = 5) in diabetic primates. Fasting blood glucose (FBG), insulin, porcine C-peptide, glycosylated hemoglobin (HbA1C), and cellular and humoral responses were followed. Results. Nonencapsulated pig islets were rejected within 7 days. A transient decrease of FBG was observed only during the 2 weeks after microencapsulated pig islet implantation under the kidney capsule. After subcutaneous transplantation of a macrodevice, diabetes was corrected up to a maximum of 6 months in five animals: FBG less than 107 mg/dL and HbA1C at 8% +/- 1.4%. Two of the five animals received a new macrodevice between 25 and 35 weeks after the first graft dysfunction (HbA1C >= 13), and diabetes was controlled for an additional 18 weeks in these animals. Although a strong humoral response was elicited after transplantation of encapsulated islets, a total impermeability of alginate 3% wt/vol to IgG was demonstrated before and up to 20 weeks after transplantation of the subcutaneous macrodevice. Conclusions. Pig islets encapsulated in a subcutaneous macrodevice can control diabetes up to 6 months without immunosuppression.
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