Bioartificial Endocrine Pancreas (Bio-AEP) for Treatment of Diabetes: Effect of Implantation of Bio-AEP on the Pancreas

Abstract

Recently, we described a diffusion chamber for a bioartificial endocrine pancreas (Bio-AEP). Pancreatic islet cells in the Bio-AEP device were isolated from the immune system of the host by an artificial barrier, while nutrients, electrolytes, oxygen, and bioactive secretory products were exchanged across this barrier. This experiment was designed to evaluate whether the diffusion chamber could be useful as a Bio-AEP in the treatment of diabetes. Six streptozotocin (STZ)-induced diabetic rats each received a diffusion chamber containing 8 x 10(6) MIN6 cells as a xenograft Bio-AEP. In the STZ diabetic rats with Bio-AEPs, a return to normoglycemia was observed up to 30 weeks after implantation, without the use of any immunosuppressant. A gradual increase in the body weight of the rats was also observed. In three STZ diabetic rats, diffusion chambers without MIN6 cells were implanted as a sham operation. The fasting blood glucose levels in these three rats remained higher than 600 mg/dl, after implantation, and they lost weight. Thirty-five weeks after implantation, the pancreata were removed from the rats that underwent xenoimplantation, those that had the sham operation, and the normal control rats. In the sham-operated animals, the exocrine tissues of the pancreata were vacuolated and pancreatic B cells were not seen in the islets. In contrast, in the pancreata from the xenoimplantation, the exocrine tissues were normal, and a few pancreatic B cells were seen in the islets. These results indicated that xenoimplantation using the Bio-AEP might retard the progress of diabetes.

Improvement of Hyperglycemia and Sexual Dysfunction in Diabetic Female Rats by an Artificial Endocrine Pancreas Developed from Mouse .BETA. Cells

“…In this study, it was possible to transplant mouse b cells into rats using Bio-AEP. This result was in agreement with those reported in previous studies [7,8]. Edamura et al (2004) reported pancreatectomized dogs could be transplanted with porcine pancreatic endocrine cells in a Bio-AEP [3].…”

“…We became interested in these reports on the Bio-AEP, since we thought it might improve -Note-sexual dysfunction induced by neuroendocrine dysfunction [11,13,19,21] based on hyperglycemia and insulin insufficiency. In addition, the Bio-AEP may make possible transplantation of b cells from different species because the Bio-AEP shows promise for long-term xenotransplantation without immunosuppression [7,8]. Therefore, the object of our study was to confirm whether or not mouse b cells could improve hyperglycemia and sexual dysfunction caused by diabetes mellitus.…”

Xenotransplantation of Porcine Pancreatic Endocrine Cells to Total Pancreatectomized Dogs

“…The structure of the Bio-AEP used in this study has previously been reported [5,10,26]. Briefly, the Bio-AEP used here was constructed with a silicon ring (4 cm in diameter and 0.5 cm thick) and two selectively semi-permeable membranes (0.1 µm pore size and 10 µm thick; Nuclepore Co., Pleasanton, California, U.S.A.) (Fig.…”

“…Within the chamber, PE-cells were cultured threedimensionally in synthetic extracellular matrix (ECM). The composition of the ECM was 1.0% agarose (Nacalai Tesque, Kyoto, Japan), 0.005% maltose-carrying polystyrene, 10 mM nicotinamide (Nacalai Tesque), and 0.15 mg/ ml type-I collagen treated to reduce the antigenicity (Cellmatrix I LA; Nitta Gelatin Co., Osaka, Japan) [5,10,26,28,29].…”

“…Over the past few decades, various types of biohybrid pancreas using hollow fiber, microcapsulation, or a diffusion chamber, have been described [1-3, 6, 18, 19, 39, 40]. We have been studying islet cell transplantation using a diffusion chamber for a bio-artificial endocrine pancreas (Bio-AEP) [10,26]. When Bio-AEPs containing MIN6 cells, a mouse insulinoma cell line, were implanted into the abdominal cavities of streptozotocin-induced diabetic rats, normoglycemia was maintained without administration of exogenous insulin and immunosuppressive drugs for more than 50 weeks [27], suggesting the efficacy of this chamber for the xenotransplantation of islet cells.…”