Fig 1.
Marginal number of islets required to ameliorate hyperglycemia in STZ-induced diabetic recipient mice by islet transplantation into the liver, beneath the kidney capsules, or into the spleen.
(A) Non-fasting blood glucose levels in STZ-induced diabetic mice (C57BL/6) transplanted with 200, 100, 50, or 25 syngeneic islets into the liver (PV), kidney capsule (KC), or spleen (SP). Individual lines represent glucose levels for each animal. The arrowhead indicates the time of graftectomy. (B) Photomicrographs of islet cells after transplantation in the spleen. Sections were stained with Haematoxylin & Eosin (H&E), anti-insulin antibody, or anti-vWF antibody. vWF+ cells are indicated by arrowheads. Scale bars: 100 μm (H&E and insulin staining); 200 μm (vWF and insulin staining). (C) The response to intraperitoneal glucose tolerance tests (IPGTT; 1 g/kg body weight) in naïve (circles), STZ-DM (triangles), and SP50 (squares) mice. Blood glucose levels were measured at the indicated time points. (D) Area under the curve following an IPGTT for each individual mouse. Values are means±SD. *p<0.05.
Fig 2.
Early inflammatory reactions after receiving the marginal number of islets into the liver, beneath the kidney capsules, or into the spleen.
(A–C) Plasma MCP-1, G-CSF, and HMGB1 levels were measured 6 hours after islet transplantation into the portal vein (PV), beneath the kidney capsule (KC), or into the spleen (SP) (n = 7). Untreated naïve mice were used as a control (n = 7). Values are means±SD. *p<0.05. (D) Photomicrographs of islet cells after transplantation in the PV, KC, or SP. Sections were stained with anti-Gr-1 or F4/80 followed by staining with Haematoxylin. Scale bars: 100 μm.
Table 1.
Plasma cytokine (chemokine) levels.
Fig 3.
Long-term effects of intra-splenic islet transplantation.
(A) Non-fasting blood glucose levels in STZ-induced diabetic mice (C57BL/6) transplanted with 25 syngeneic islets in the spleen (SP) and 100 syngeneic islets under the kidney capsule (KC). Individual lines represent glucose levels in each animal. (B) Photomicrographs of transplanted islet cells in the SP on day 290. Sections were stained with anti-insulin antibody followed by hematoxylin. Scale bars: 100 μm. (C) Insulin content was measured after islet transplantation on days 0 (n = 6) and 280 (n = 6). Values are means±SD. *p<0.0001.
Fig 4.
Tlx1-related gene expression analysis.
(A) Tlx1 (Hox11)-related gene expression levels were significantly altered. A hierarchical clustering image reveals differences between Samples 1, 2, and 3. (B) Photomicrographs of transplanted islet cells in the spleen on days 0, 154, and 290. Sections were stained with anti-insulin antibody (green) and anti-Rrm2b antibody (red). Scale bars: 100 μm. The yellow boxed regions in the second column were enlarged, and the scale bars are 200 μm. (C) Photomicrographs of transplanted islet cells in the spleen on days 0, 154, and 290. Sections were stained with anti-insulin antibody (green) and anti-Pla2g2d antibody (red). Scale bars: 100 μm. The yellow boxed regions in the second column were enlarged, and the scale bars are 200 μm.