Normal relationship of beta- and non-beta-cells not needed for successful islet transplantation

Abstract

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