Xenotransplantation of exendin-4 gene transduced pancreatic islets using multi-component (alginate, poly-L-lysine, and polyethylene glycol) microcapsules for the treatment of type 1 diabetes mellitus

摘要

This study proposed that microencapsulation of exendin-4 gene transduced islets using alginate, poly-L-lysine, and polyethylene glycol could lead to increased viability and functionality of islets in a rat to mouse xenograft model. The stability of the microcapsules was determined using an osmotic pressure test and a rotational stress test. Exendin-4 gene was transduced into pancreatic islets using lenti-viral vectors and the transduced islets were encapsulated using multi-component microcapsules mentioned above. Both viability and functionality of microencapsulated islets were evaluated in both in vitro and in vivo xenograft model. The viabilities of the unmodified islets (control) and the exendin-4 transduced islets (test) on 14th day were 18.6 ± 11.1 and 49.2 ± 13.4%, respectively (p < 0.05). The stimulation index of the control and the test groups was 2.3 ± 1.7 and 3.0 ± 1.6, respectively. The mean survival times (MST) of the control and the test groups were 20.2 ± 8.0 and 35.2 ± 10.0 days, respectively (p < 0.05). Significant differences in MST suggested that transduction of exendin-4 gene had a great potential to increase the function of encapsulated islets. In conclusion, exendin-4 gene transduced islets encapsulated by poly(ethylene glycol) conjugated alginate/PLL microcapsules significantly improved both viability and functionality of encapsulated islets.