A Novel Pre-Vascularized Subcutaneous Site Safely Accommodates Stem Cell Derived Therapies for Treating Diabetes

Islet transplantation has become an important treatment modality for Type 1 Diabetes Mellitus (T1DM); nonetheless, the procedure may be limited by donor availability. An alternative has been the increasing use of cellular therapies derived from human Embryonic Stem Cells (hESC), showing very promising results in maturation, yield and ultimately, in insulin secretion in response to adequate stimuli. We recently developed a new technique for cellular transplantation under the skin. This manuscript evaluates the capabilities of the pre-vascularized DeviceLess (DL) site to allow transplantation of Pancreatic Endoderm (PE) cells differentiated from hESC to treat diabetes mellitus. Fifty immunodeficient mice, n = 25 diabetic and n = 25 non-diabetic, were transplanted with PE cells. Animals were followed for 22 weeks and grafts were retrieved to evaluate engraftment and subsequent maturation. Diabetic mice showed slightly better engraftment (48% vs. 36%, p = 0.19) and secreted higher concentration of human C-peptide upon glucose stimulation (0.32 ± 0.15 ng/mL vs. 0.13 ± 0.09 ng/mL, p = 0.30), although differences were not significant. This maturation was not sufficient to successfully reverse diabetes. Monomorphic cystic changes were detected in 12% and 8%, respectively (diabetics vs. non-diabetics, p = 0.32) and all grafts seemed to be adequately contained by the surrounding collagen wall within the DL space. Our findings support the capabilities of the DL site to host PE cells and allow safe maturation as a new strategy to treat diabetes.