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

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

Correspondence: gordon.weir{at}joslin.harvard.edu

Objective.: Islets are comprised 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.

Research Design and Methods.: Rat islets were dispersed and beta cells were purified by FACS sorting according to their endogenous fluorescence. After reaggregation, 600 islet equivalents of the purified beta cell aggregates were implanted into diabetic SCID mice.

Results.: 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; prior to and 12 weeks after transplantation the beta cell enriched aggregates comprised of 95% beta cells and 5% endocrine non beta cells. However, islet grafts, despite originally having been comprised of 75% beta cells and 25% endocrine non-beta cells, comprised of just 5% endocrine non-beta cells after transplantation, indicating a loss of these cells.

Conclusion.: 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.

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