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

Abstract

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