Normal Relationship of - and Non– -Cells Not Needed for Successful Islet Transplantation

Islets are composed mostly of -cells, and therefore stem cell research has concentrated on generating purified -cells, neglecting the other endocrine cell types in the islet. We investigated the presence of endocrine non– cells after islet transplantation. In addition, we studied whether the transplantation of pure -cells, in volumes similar to that used in islet transplantation, would suffice to reverse hyperglycemia in diabetic mice. Rat islets were dispersed and -cells were purified by fluorescence-activated cell sorting according to their endogenous fluorescence. After reaggregation, 600 islet equivalents of the purified -cell aggregates were implanted into diabetic SCID mice. In mice implanted with -cell–enriched aggregates, the hyperglycemia was reversed and good graft function over a 12-week period was observed with regard to glucose and insulin levels, glucose tolerance tests, and graft insulin content. The endocrine cell composition of the -cell–enriched aggregates remained constant; before and 12 weeks after transplantation, the -cell–enriched aggregates comprised 95% -cells and 5% endocrine non– -cells. However, islet grafts, despite originally having comprised 75% -cells and 25% endocrine non– -cells, comprised just 5% endocrine non– -cells after transplantation, indicating a loss of these cells. -Cell–enriched aggregates can effectively reverse hyperglycemia in mice, and transplanted intact islets are depleted in non– -cells. It is therefore likely that islet non– -cells are not essential for successful islet transplantation. Diabetes 56:2312–2318, 2007