We 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.