Suppression of Epithelial-to-Mesenchymal Transitioning Enhances Ex Vivo Reprogramming of Human Exocrine Pancreatic Tissue Toward Functional Insulin-Producing β-Like Cells

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FIG. 8.
FIG. 8.

Reprogrammed insulin-producing cells prevent STZ-induced diabetes in vivo. A: Body weight and blood glucose levels were measured in NOD/SCID mice grafted with transdifferentiated cells or exocrine pancreatic cells or in nongrafted mice (Ctrl) over a 38-day period after surgery. A single dose (150 mg/kg) of STZ was administered 1 day before surgery. Transdifferentiated cells, n = 5; exocrine pancreatic cells, n = 3; control, n = 2. B: Serum C-peptide levels were measured in NOD/SCID mice grafted with transdifferentiated cells or exocrine pancreatic cells and in nongrafted mice (Ctrl) after a 4-h starvation period (fast) or with ad libitum feeding (fed) conditions. Transdifferentiated cells, n = 5; exocrine pancreatic cells, n = 3; control, n = 2. C: Immunostaining for insulin and glucagon of grafted kidneys after kidney removal. Yellow dashed lines indicate the border between the kidney (k) and the graft. The red circle in panel a indicates the difference in glucagon staining observed within the cluster. A 5× higher magnification of the cells inside this circle is shown in panel c; 10× higher magnifications of the cells inside (panel e) and outside (panel f) the circle are shown. Panel d shows a 5× higher magnification of insulin staining within the area marked by the red square in panel b. A 10× higher magnification of insulin-positive cells present in the center of the cluster is shown in panel g. Scale bar for panels a and b = 100 µm. Scale bar for panels cg = 20 µm. D: Immunofluorescent staining for Pdx1 in kidneys grafted with transdifferentiated cells. Scale bar = 50 µm. A 5× higher magnification inlet is shown. Ctrl, control; Exoc Cells, exocrine pancreatic cells; GLC, glucagon; INS, insulin; Transdif Cells, transdifferentiated cells.

This Article

  1. Diabetes vol. 62 no. 8 2821-2833