Upper panel: expression of markers in HAE cells and HAM cells. Lane 1: HAE cells, lane 2: pancreatic induced HAE cells, lane 3: HAM cells, lane 4: pancreatic induced HAM cells, middle panel: changes in blood glucose level (a) and body weight (b) of mice. Sham-operated diabetic mice (filled triangle, n = 6), HAE transplanted mice (filled circle, n = 11), and HAM transplanted mice (filled square, n = 9). Lower panel: detection of human-specific β-2 microglobulin. Lane 1: mouse genomic DNA, lane 2: human genomic DNA, lane 3: HAE transplanted mice spleen, lane 4: pancreas, and lane 5: liver. The figure is modified from Wei JP et al. 
6 Diabetes Treatment Using Amnion Cells
Several studies have reported the possibility of diabetes treatment using amnion-derived cells. Amnion-derived cells were induced into insulin-producing cells in vitro by treating with nicotinamide and other supplements. The expression level of pancreatic β-cell related genes, insulin, glucagon, somatostatin, Pdx-1, pancreas and duodenum homeobox-4 (Pdx-4), paired box gene 6 (Pax-6), NK2 transcription factor-related locus 2 (Nkx-2.2), NK6 transcription factor-related locus1 (Nkx6.1), Islet-1(Isl-1), glucokinase (GCK), glucose transporter-2 (Glut2), and Neuro D were all increased after the pancreatic induction in vitro (Fig. 23.1 upper panel, Fig. 23.2, [22–24]).
Histological analysis of implanted mice. (a, c, e, g) anti-human-β-2 microglobulin, (b, d, f, h) anti-human insulin. (a, b) Normal mouse spleen (c, d), diabetic mouse spleen (e, f), HAE-transplanted mouse spleen (g), human lung, and (h) human pancreas. Original magnification: ×200. The figure is modified from Wei JP et al. 
To see the effect of amnion derived cells in vivo, a diabetic mouse model was made by a single IP injection of streptozotocin (STZ) into severe combined immunodeficient (SCID) mice. The body weight of STZ-injected mice was lower than that of normal mice and the blood glucose level increased after injection. HAE cells or HAM cells were implanted into the spleens of diabetic mice. Body weight of HAE cell-implanted mice increased gradually and was significantly higher than that of sham-operated mice. The blood glucose level of HAE cell-implanted mice gradually decreased to a normal level, which was significantly lower than that of sham-operated mice (Fig. 23.1 middle panel, ).
The body weight of HAM cell-implanted mice decreased but was significantly higher than that of sham-operated diabetic mice. The blood glucose level of HAM-implanted mice was also significantly lower than that of sham-operated diabetic mice (Fig. 23.1 middle panel, [22, 23]). Transplanted human cells were detected 1 month after the transplantation by immunohistochemistry and RT-PCR (Fig. 23.1 lower panel and Fig. 23.2, ). The results indicated that the implanted human cells had been integrated into the spleen and migrated into the liver and pancreas. Also, they had differentiated into insulin-secreting cells within 1 month. However, more efficient induction methods will be investigated for clinical use, such as gene introduction.
The therapeutic potential of both amnion epithelial cells and mesenchymal cells for diabetes has been reported. They appear to be cell sources for cell therapy and to be more useful than ES cells or iPS cells or other somatic stem cells as amnion cells could be used for allogeneic transplantation. Amnion-derived cells may be a good cell source for the transplantation therapy of diabetes.
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