Enhancement of in vitro and in vivo function of agarose-encapsulated porcine islets by changes in the islet microenvironment
| Autor: | Robert W. Holdcraft, Eric D. Meyer, Richard D. Hall, Barry Smith, Melissa A. Bautista, Horatiu V. Vinerean, Lisa Circle, Lawrence S. Gazda, Melissa A. Laramore, Prithy C. Martis, Hollie Adkins, Steven G. Harbeck |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty endocrine system endocrine system diseases Swine Xenotransplantation medicine.medical_treatment Transplantation Heterologous Biomedical Engineering Islets of Langerhans Transplantation lcsh:Medicine Diabetes Mellitus Experimental Rats Sprague-Dawley chemistry.chemical_compound Islets of Langerhans In vivo Internal medicine medicine Animals Pancreas Cell Proliferation Transplantation geography geography.geographical_feature_category Insulin Sepharose lcsh:R Capsule Cell Biology Islet Molecular biology In vitro Rats Endocrinology Diabetes Mellitus Type 1 chemistry Agarose Female |
| Zdroj: | Cell Transplantation, Vol 23 (2014) |
| ISSN: | 1555-3892 |
| Popis: | The transplantation of porcine islets of Langerhans to treat type 1 diabetes may provide a solution to the demand for insulin-producing cells. Porcine islets encapsulated in agarose–agarose macrobeads have been shown to function in nonimmunosuppressed xenogeneic models of both streptozotocin-induced and autoimmune type 1 diabetes. One advantage of agarose encapsulation is the ability to culture macrobeads for extended periods, permitting microbiological and functional assessment. Herein we describe optimization of the agarose matrix that results in improved islet function. Porcine islets (500 IEQs) from retired breeding sows were encapsulated in 1.5% SeaKem Gold (SG), 0.8% SG, or 0.8% Litex (Li) agarose, followed by an outer capsule of 5% SG agarose. Insulin production by the encapsulated islets exhibited an agarose-specific effect with 20% (0.8% SG) to 50% (0.8% Li) higher initial insulin production relative to 1.5% SG macrobeads. Insulin production was further increased by 40–50% from week 2 to week 12 in both agarose types at the 0.8% concentration, whereas islets encapsulated in 1.5% SG agarose increased insulin production by approximately 20%. Correspondingly, fewer macrobeads were required to restore normoglycemia in streptozotocin-induced diabetic female CD(SD) rats that received 0.8% Li (15 macrobeads) or 0.8% SG (17 macrobeads) as compared to 1.5% SG (19 macrobeads). Islet cell proliferation was also observed during the first 2 months postencapsulation, peaking at 4 weeks, where approximately 50% of islets contained proliferative cells, including β-cells, regardless of agarose type. These results illustrate the importance of optimizing the microenvironment of encapsulated islets to improve islet performance and advance the potential of islet xenotransplantation for the treatment of type 1 diabetes. |
| Databáze: | OpenAIRE |
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