Comparative study of microencapsulated rat islets implanted in different diabetic models in mice

Microencapsulated rat islets of Langerhans (alginatepolylysine microcapsules) were implanted into the peritoneal cavity of diabetic mice (500 rat islets per mouse) in order 1) to evaluate the ability of this xenograft in correcting hyperglycemia in different models of diabetes and 2) to examine the implanted material recovered from the recipients after several weeks. 1) In the high-dose streptozotocin model in Balb/c mice (n = 14), 6 had a sustained (over one month) decrease in plasma glucose concentration from 401 +/- 7 to 171 +/- 7 mg/dl, with no effect in the other. 2) In the low dose streptozotocin model in C57BL/6J mice (n = 17), plasma glucose levels decreased in 9 mice, from 439 +/- 27 to 180 +/- 30 mg/dl, and remained below 250 mg/dl up to 60 days. In 8 mice, only a transient effect was observed. Empty capsule transplantation had no effect. Plasma insulin in successfully transplanted mice was higher in fed than in fasted state. 3) Microencapsulated rat islets had no effect on plasma glucose in male NOD mice made diabetic by cyclophosphamide treatment (n = 10). Thus, microencapsulated rat islets can improve the diabetic state in some, but not all diabetic mice. In this study, microcapsules were consistently surrounded by an inflammatory reaction, which remains a major concern.