Fig. 5. In vivo characterization of EM CC in xenogeneic diabetic mouse and NHP recipient model.

(A) Schematic of human islet donor and naked (black) and CC EM (green) islets. (B) Schematic of diabetic recipient model NSG mouse and NHP (left) and a photograph of NHP omentum with CC EM human islets. (C) Phase-contrast image of CC EM human islets (left; scale bar, 200 μm); phase-contrast image of dithizone-stained CC EM human islets (right; scale bar, 200 μm). (D) GSIS of naked (black) and CC DM (green) human islets as absolute insulin (L1, 2.8 mM glucose; H, 20 mM glucose; L2, 2.8 mM glucose; KCl, 2.8 mM glucose and 30 mM KCl), stimulation index (H/L1), and delta (H-L1) (n = 3 technical repeats). (E) Perifusion (dynamic GSIS) of naked (black, n = 3 technical repeats) and CC EM (green, n = 3 technical repeats) human islets (3G, 3 mM glucose; 11G, 11 mM glucose; KCl, 25 mM KCl). (F) Stimulation index calculated as insulin secretion rate during high step divided by insulin secretion rate during first low step. Delta is calculated as insulin secretion rate during high step minus insulin secretion rate during first low step. (G) Daily blood glucose readings of mice receiving 4000 IEQ of naked (black, n = 3) and CC EM (green, n = 3) human islets and stimulated C-peptide measurement (n = 3) for both conditions. (H) Metabolic data for diabetic NHP recipient H17C39 including fasting (solid green line) and prandial (dashed green line) blood glucose and daily insulin requirements (pink, shaded) in the left graph and serum C-peptide in the right graph. (I) Light microscopy images of H&E-stained (left) and immunofluorescence confocal micrographs [CD31 in green, α smooth muscle actin (αSMA) in red, nuclei in blue] of explanted omental tissue containing islet grafts (scale bars, 200 μm).