AbstractWe previously reported that allogeneic, intraperitoneally administered “Neo-Islets,” composed of cultured pancreatic islet cells co-aggregated with high numbers of immunoprotective and cytoprotective Adipose-derived Stem Cells, reestablished, through omental engraftment, redifferentiation and splenic and omental up-regulation of Regulatory T-cells, normoglycemia in autoimmune Type-1 Diabetic Non-Obese Diabetic (NOD) mice without the use of immunosuppressive agents or encapsulation devices. Based on these observations, we are currently testing this Neo-Islet technology in an FDA guided Pilot Study (INAD 012-776) in insulin-dependent, spontaneously diabetic pet dogs by the intraperitoneal administration of 2×10e5 Neo-Islets/kilogram body weight to metabolically controlled (blood glucose, triglycerides, thyroid and adrenal functions) animals under sedation and local anesthesia and ultrasound guidance. We report here initial observations on the first 4 Neo-Islet-treated, insulin dependent pet dogs that are now in the intermediate-term follow-up phase of the study (> 6 months post treatment). Current results indicate that in dogs, Neo-Islets appear to engraft, redifferentiate and physiologically produce insulin, and are neither rejected by auto- or allo-immune attacks, as evidenced by (a) an absent IgG response to the allogeneic cells contained in the administered Neo-Islets, and (b) progressively improved glycemic control that achieves up to a 50% reduction in daily insulin needs paralleled by a significant fall in serum glucose levels. This is accomplished without the use of anti-rejection drugs or encapsulation devices. No adverse or serious adverse events related to the Neo-Islet administration have been observed to date. We conclude that this minimally invasive therapy has significant translational relevance to veterinary and clinical Type 1 Diabetes Mellitus by achieving complete and at this point partial glycemic control in two species, i.e., diabetic mice and dogs, respectively.
Enzyme Histochemistry in Experimental Diabetes Mellitus. The findings of several enzymez activities in pancreatic islet cells
