As expected, control STZ-treated mice characteristically exhibited hyperphagia, polydipsia, excess weight loss and marked hyperglycaemia which were temporarily moderated during the period of insulin treatment. Implantation of 1 1.1B4 cell suspensions 17-Hydroxyprogesterone or pseudoislets yielded vascularised cell masses (data MMP9 not included) which restored plasma insulin concentrations and reversed the hyperglycaemic state. tissues were collected for analysis. Insulin and glucagon contents of plasma and tissues were measured by insulin radioimmunoassay and chemiluminescent enzyme-linked immunosorbance assay respectively. Histological analyses of pancreatic islets were carried out by quantitative fluorescence immunohistochemistry staining. RESULTS Both pseudoislet and cell suspension implants yielded well vascularised -cell masses of comparable insulin content. This was associated with progressive amelioration of hyperphagia ( 0.05), polydipsia ( 0.05), body weight loss ( 0.05), hypoinsulinaemia ( 0.05), hyperglycaemia ( 0.05 – 0.001) and glucose tolerance ( 0.01). Islet morphology was also significantly improved in both groups of transplanted mice, with increased -cell ( 0.05 – 0.001) and decreased alpha cell ( 0.05 – 0.001) areas. Whereas mice receiving 1.1B4 cell suspensions 17-Hydroxyprogesterone eventually exhibited hypoglycaemic complications, pseudoislet recipients displayed a more gradual amelioration of diabetes, and achieved stable blood glucose control much like non-diabetic mice at the end of the study. CONCLUSION Although further work is needed to address security issues, these results provide proof of concept for possible therapeutic applicability of human -cell collection pseudoislets in diabetes. the portal vein[8]. While less risky than whole organ transplantation, ITx is limited by the requirement for immunosuppression to prevent rejection and promote long-term islet graft functionality but the majority of patients still revert to insulin use within five years of treatment[11,12]. Nevertheless, ITx can provide temporary insulin independence and even partial graft function can prevent dangerous hypoglycaemic events[8,13,14]. Regrettably, pancreatic 17-Hydroxyprogesterone donors are scarce and current practices often require use of islets from 17-Hydroxyprogesterone two or more individual donors. This practice is not practical on a large scale and so there is a great impetus to find alternative solutions especially given that implant function also frequently fails with time[8]. One approach to providing a sustainable supply of insulin releasing tissue for transplantation is usually to generate insulin-producing cells from stem cells or to engineer cell-lines which mimic the functional response of normal human pancreatic -cells[15-18]. Over the years, many rodent -cell lines have been created by methods such as exposure of main rodent -cells to radiation or transfection with oncogenic viral vectors such as SV40[19-24]. While such cell-lines have proven priceless in basic islet research their xenogeneic properties limit their therapeutic utility. Consequently, more recent endeavours have been focused on the creation of insulin-releasing cell-lines from human -cells[25,26]. Regrettably, this has proven to be extremely difficult as human -cells tend to proliferate poorly and undergo quick dedifferentiation when cultured unless specified normally. Diabetes was induced by intraperitoneal administration of streptozotocin (165 mg/kg) after an 8 h fast. Hyperglycaemia was controlled with rigorous insulin therapy (15 mg/kg body weight intraperitoneal bovine insulin every 8 h) prior to and during the early engraftment period as indicated in the Figures. Suspensions of 1 1.1B4 cells (1 107 cells/mL) were administered in 500 L serum-free Roswell park memorial institute (RPMI) medium subscapularly into adipose tissue deposit at back of the neck using a 25-G needle. For pseudoislet implantation, harvested pseudoislets were resuspended at a density of 2000 pseudoislets per ml and 500 L was injected to the same location using an 18-G needle. Control mice received vehicle only. Food intake, water intake and body weight were monitored daily while blood glucose was measured once every 3 d using Ascensia contour glucose strips (Bayar, Uxbridge, United Kingdom). At the end of the study, glucose tolerance was determined by measuring blood glucose and plasma insulin levels after glucose administration (18 mmol/kg 0.05. RESULTS Effects on food and fluid intake, body weight and blood glucose Streptozotocin diabetes caused significant increases in food and fluid intake when compared to nondiabetic controls (0.05, 0.01, 0.001, Figure ?Figure2A2A and B). Implantation of 1 1.1B4 cell suspensions or pseudoislets had small inhibitory effects on daily and cumulative food intake (Determine ?(Figure2A).2A). 1.1B4 pseudoislet transplantation significantly (0.05) decreased fluid intake from day 18 post-implantation compared to the marked polydipsia exhibited by diabetic 17-Hydroxyprogesterone controls (Determine ?(Figure2B).2B). Fluid intake of cell suspension recipients did not significantly differ from control diabetic.