Treatment of Diabetes by Xenogeneic Islets Without Immunosuppression: Use of a Vascularized Bioartificial Pancreas

Abstract

Tight glycemic control by intensive insulin therapy effectively delays the onset and slows the progression of diabetic complications but is associated with frequent dose adjustments and a high incidence of hypoglycemia. Successful pancreas transplantation corrects abnormal glucose metabolism but subjects patients to morbidity and mortality associated with chronic immunosuppression. A vascularized artificial pancreas device containing pancreatic islets is designed to provide glycemic control without immunosuppression. We report here that devices seeded with porcine islets implanted into pancreatectomized severely diabetic dogs maintained a marked improvement in glycemic control with reduced exogenous insulin requirements for up to 9 months with improved glucose tolerance and a reduction in glycosylated hemoglobin levels. No immunosuppression was used. Thus, use of a vascularized artificial pancreas containing xenogeneic porcine islets could be an alternative to intensive insulin therapy and pancreatic transplantation in treating diabetic patients before the development of severe diabetic complications.

Initial clinical results of the bioartificial kidney containing human cells in ICU patients with acute renal failure

“…The overall ratio for all 10 patients averaged 0.903 ± 0.050 (SE). The proximal tubule converts 25-OH-Vit D 3 to the most active vitamin D derivative, 1,25-(OH) 2 -Vit D 3 [29]. The loss of this proximal tubule hormonal ac- Replacement of proximal tubule function should result in higher 1,25-(OH) 2 -Vit D 3 plasma levels.…”

“…This form of treatment is dependent on cell and tissue culture methodologies to expand and supply stem/progenitor cells to replace important differentiated processes damaged or lost in various disease states. Recent approaches have made progress by placing cells into hollow-fiber bioreactors or encapsulating membranes as a means to deliver cell activities to a patient [2,3]. A reasonable extension of this approach is to add cell therapy to the current continuous renal replacement therapy (CRRT) [4].…”

Scientific and Political Impediments to Successful Islet Transplantation

“…Thus, a device with many parallel hollow fibers is fed by an artery and drained by a vein. One group has tested this approach extensively in dogs and has been able to normalize glucose levels with allografted islets for prolonged periods of time without immunosuppression; they have even had partial success with porcine islets (84). These important experiments provide proof for the principle that immunobarrier membranes can protect islets from xenograft rejection.…”

Progress and challenges in macroencapsulation approaches for type 1 diabetes (T1D) treatment: Cells, biomaterials, and devices

“…First demonstration of the long-term use of a bioartificial pancreas in a large animal using a vascular perfusion device was demonstrated in the 1990s (Maki et al, 1991a, b, 1993, 1996b). Maki and co-workers developed a hybrid pancreas device, which contains an acrylic housing with islets separated from the common iliac artery and vein in dogs through the semipermeable membrane (80kDa) (Fig.…”