In vivo depletion of pancreatic acinar tissue simplifies islet preparation for transplantation

A copper deficient diet is reported to reduce acinar tissue in vivo. We investigated the suitability of this method to reduce in vivo acinar tissue mass of a rat pancreas prior to transplantation of dispersed pancreatic tissue. We also studied islet function in the acinar depleted pancreas and the outcome of transplantation of islets from such pancreata. Eighty-two Wistar Furth rats were divided into two groups with 42 animals in the control group receiving regular diet, and 40 receiving copper deficient diets (Cudt) plus tetraethylene- pentamine penta-hydrochloride (TEPA) as a chelating agent. All animals in the control group and 34 (85%) in the Cudt group tolerated this diet and survived for 60 days or longer. At the end of 60 days, all experimental animals were converted to a regular diet until the pancreata were harvested for islet transplantation. Eight rats in the Cudt group, which were converted to a regular diet for 2 weeks, and 2 in the control group were randomly selected and sacrificed to study the pancreas for acinar depletion and islet morphology. An intravenous glucose tolerance test (IVGTT) in the control group (n=24) and the Cudt group (n=25) showed K-values of 1.891+/-0.7 and 1.107+/-0.47, respectively (P-ns). Histology of pancreata showed normal acinar tissue in the control group and reduction of acinar tissue mass in the Cudt group. Furthermore, immunohistochemistry for insulin, glucagon, and somatostatin showed positively staining, while amylase was negative in the Cudt group, compared with the positive stain for cells in the control group. Standard collagenase digestion of the pancreas showed islets were surrounded by scant amounts of acinar tissue in the Cudt group compared with the control group. The islet count in the control group was 523+/-126 and 611+/-52 in the Cudt group. The mean volumes of dispersed pancreatic tissue were 0.3875+/-0.14 and 0.0668+/-0.029 ml per rat in the control and Cudt groups, respectively (P