Xenotransplantation of agarose-microcapsulated porcine islets for the treatment of diabetes mellitus

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Abstract

BACKGROUND:

Previous studies have shown that agarose-microcapsulated adult porcine islets had some effective biology activities in vitro. However, the biologic effects of such microcapsule materials in transplanted animal need to be further evaluated.

OBJECTIVE:

To observe the effect of intraperitoneal transplantation of agarose-microcapsulated adult porcine islets in experimental diabetic rats.

DESIGN, TIME AND SETTING:

A controlled observational experiment was performed at the Central Laboratory of Zhengzhou University from December 2007 to December 2008.

MATERIALS:

Agarose was used to make microencapsules which were used to coat adult porcine islets by phase-separation method.

METHODS:

The islets with or without agarose were cultured in RPMI1640, and the culture liquid was changed every two days. The supernatant was collected on the first and fifth days to determine insulin content. The islets placed in different solutions, including 5.6 mmol/L glucose, 16.6 mmol/L glucose, and 10.0 mmol/L alkali, were used for insulin stimulated test by radioimmunoassay. A total of 27 diabetic rats were randomly divided into three groups: control group, unencapsulated islets transplantation group and encapsulated islets transplantation group, injecting saline, (0.9-1.6)×103 unencapsulated islets, and (0.8-1.7)×103 encapsulated islets, respectively.

MAIN OUTCOME MEASURES:

the difference of basic insulin of microencapsulated islets with agarose; the activity of microencapsulated islets responded to glucose and alkali; the subsistence time of rats accepted microencapsulated islets transplantation.

RESULTS:

The islets could secrete insulin consecutively for a month, and the cells in capsules survived very well without autolysis and breakage. At day 2 after culture, the islets had marked reactions to the stimulation from glucose in high concentration and theophylline. The released amount of insulin was 1.96 times and 2.58 times as much as that of glucose at a low concentration respectively (P < 0.01). On the 7th day after transplantation, the mean levels of the blood glucose in the three groups were (21.61 ± 1.21) mmol/L, (19.11 ±2.39) mmol/L and (13.67 ±1.43) mmol/L, respectively. There was significant difference between the encapsulated islets transplantation group and other two groups; in addition, the encapsulated islets transplantation group survived much longer than the other two groups.

CONCLUSION:

Agarose-microcapsulated adult porcine islets may survive in diabetic rats and has effective bioactivity.

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