Xenotransplantation of Porcine Pancreatic Endocrine Cells to Total Pancreatectomized Dogs

Abstract

ABSTRACT. Xenotransplantation of porcine pancreatic endocrine (PE) cells in a diffusion chamber, a bioartificial endocrine pancreas (Bio-AEP), was conducted to total pancreatectomized dogs. Six pancreatectomized dogs were divided into two groups of 3 dogs each. In three dogs of the control group, exogenous insulin was administered twice a day for 30 weeks to maintain fasting blood glucose (FBG) levels within the normal range. The remaining three dogs were implanted with Bio-AEPs (implantation group), in addition to daily insulin administration. In the implantation group, Bio-AEPs containing 1.3 to 1.8 × 10 7 cells per kg of body weight of the recipient were implanted without fixation into the abdominal cavity. In the control group, exogenous insulin requirements did not decrease during the experimental period, whereas it significantly decreased for a certain period (3, 11, 17 weeks) after implantation in all implanted dogs. In the implantation group, laparotomy was performed after FBG and the exogenous insulin requirement increased again and Bio-AEPs were removed. Two Bio-AEPs were completely destroyed, and the remaining one was encapsulated by thin fibrous tissue. In this dog, effusion was present within the capsule, but the Bio-AEP was not destroyed. Histopathologically, the necrosis, presumably caused by hypoxia, of the PE-cells was observed on transmission electron microscopy. In conclusion, Bio-AEP could function for a certain period after implantation in this study. However, more preclinical researches should be needed to apply this technique for the treatme nt of diabetic dogs.

Prevalence of Porcine Endogenous Retrovirus in Domestic Pigs in Japan and Its Potential Infection in Dogs Xenotransplanted with Porcine Pancreatic Islet Cells

“…Recipients: Five Beagle dogs that had been transplanted with approximately 1.0 to 2.0 × 10 8 porcine PE-cells were used [4]. Porcine PE-cells were embedded in the diffusion chamber type Bio-AEP constructed of a silicon ring and two nucleopore membranes with a pore size of 0.1 µm [4,10].…”

“…Porcine PE-cells were embedded in the diffusion chamber type Bio-AEP constructed of a silicon ring and two nucleopore membranes with a pore size of 0.1 µm [4,10]. Bio-AEP was implanted into the abdominal cavity of the dog without fixation.…”

“…In the previous study, xenotransplantation of Bio-AEP with porcine PE-cells into experimentally induced diabetic dogs was partially successful to reverse the hyperglycemic condition [4]. Clinical application of islet xenotransplantation may be possible in the future.…”

Pravastatin Improves Glucose Regulation and Biocompatibility of Agarose Encapsulated Porcine Islets following Transplantation into Pancreatectomized Dogs

“…Kin et al demonstrated insulin independence for 6–119 days in pancreatectomized dogs receiving xenogeneic porcine islets encapsulated in agarose and polystyrene sulfonic acid [10]. A bioartificial endocrine pancreas consisting of porcine islets contained in an agarose matrix within semipermeable membranes was also shown to reduce insulin requirements in pancreatectomized dogs for up to 17 weeks [11]. …”

Enhancing Clinical Islet Transplantation through Tissue Engineeering Strategies

“…65,69 Extravascular devices refer to macroencapsulated cells that are implanted outside of the vasculature, e.g., subcutaneously, intraperitoneally, or in the omentum. Although these devices, such as hollow fibers, diffusion chambers, and polymeric sheets, yielded encouraging results in rodents [70][71][72][73][74][75][76][77] and canines, [78][79][80] their large size and exclusive reliance on diffusive transport resulted in islet dysfunction and device failure in the long term. Mathematical modeling predicts inadequate transport profiles, indicating scalability of these devices to larger animal models will be problematic after islet density optimization, thereby rendering such implants bulky or requiring multiple devices.…”