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

¹ Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center, Boston, Massachusetts
² Department of Medicine, Harvard Medical School, Boston, Massachusetts
³ Division of Reproduction and Endocrinology, Guy's Campus, King's College London, United Kingdom

Address correspondence and reprint requests to Gordon C. Weir, MD, Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215. E-mail: gordon.weir{at}joslin.harvard.edu

Abbreviations: IE, islet equivalent; IPGTT, intraperitoneal glucose tolerance test

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

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