Fig. 5
Comparison of transplantation efficiency between transplantation of insulin-producing cell (IPC) sheets (one or three sheets) on the liver surface and injection of IPCs through the portal vein. a Photographs of experimental protocols of IPC portal vein injection (upper) and IPC sheet transplantation on the liver surface of immune-deficient diabetic mouse. b Distribution of transplanted or injected IPCs in mice. The distribution of transplanted IPCs in recipient mice was examined with an in vivo imaging system. Optical imaging of IPC labeled Qdot 800 in vivo and ex vivo. Fluorescence color images were processed using Living Image V.3.2. A grayscale body image was collected and overlaid by a pseudo-color image representing the spatial distribution of the detected photons. c Fluorescence images of IPCs and IPC sheet before transplantation (left). Seven days after treatment, the liver, kidney, spleen, pancreas, heart, and lung were harvested, and ex vivo fluorescent images were acquired (right). d Human insulin levels in blood serum from mice transplanted with one or three cell sheets and PV injected. Diabetic mice without transplants were negative controls. N = 4 or 5. The asterisk symbol (*) indicates a significant increase in the insulin level of IPC sheets (three layers) upon IPC injection at each time point; P < 0.05. e Therapeutic effects of insulin-producing cell (IPC) sheet transplantation in diabetic nude mice. Two weeks before transplantation, mice were induced with insulin-dependent diabetes using streptozotocin (180 mg/mL). At day 0, diabetic nude mice were transplanted with three IPC sheets or injected with 106 IPCs through the portal vein. Diabetic nude mice and wild-type mice were used as negative and positive controls, respectively. At different time points, non-fasting blood glucose levels and body weights were measured in sheet transplanted on liver surface, portal vein injected IPCs, and diabetic control (n = 5). The asterisk (*) indicates a significant increase in body weight upon IPCs; P < 0.05. f Immunohistochemical analyses of PDX1and insulin in the liver at 7, 14, and 28 days after transplantation of IPCs and IPC sheets. Arrows indicate positive cell staining. Original magnifications are × 200 (PDX1) and × 400 (insulin). g Immunohistochemical analyses of CD31 in the liver at 28 days after transplantation of IPC sheets. Arrow indicated positive cell staining. Original magnifications are × 200