Denis Dufrane1, Rose-Marie Goebbels, Pierre Gianello. 1. Laboratory of Experimental Surgery, Université catholique de Louvain, Faculté de Médecine, Brussels, Belgium. denis.dufrane@uclouvain.be
Abstract
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.
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.
Authors: Stephen T Bartlett; James F Markmann; Paul Johnson; Olle Korsgren; Bernhard J Hering; David Scharp; Thomas W H Kay; Jonathan Bromberg; Jon S Odorico; Gordon C Weir; Nancy Bridges; Raja Kandaswamy; Peter Stock; Peter Friend; Mitsukazu Gotoh; David K C Cooper; Chung-Gyu Park; Phillip OʼConnell; Cherie Stabler; Shinichi Matsumoto; Barbara Ludwig; Pratik Choudhary; Boris Kovatchev; Michael R Rickels; Megan Sykes; Kathryn Wood; Kristy Kraemer; Albert Hwa; Edward Stanley; Camillo Ricordi; Mark Zimmerman; Julia Greenstein; Eduard Montanya; Timo Otonkoski Journal: Transplantation Date: 2016-02 Impact factor: 4.939
Authors: Kate R Mueller; A N Balamurugan; Gary W Cline; Rebecca L Pongratz; Rebecca L Hooper; Bradley P Weegman; Jennifer P Kitzmann; Michael J Taylor; Melanie L Graham; Henk-Jan Schuurman; Klearchos K Papas Journal: Xenotransplantation Date: 2013-02-05 Impact factor: 3.907