Fig. 8. Therapeutic effects of the transplantation of hiPSC-EPO–producing cells on renal anemia in adenine-treated mice. Therapeutic effects of the transplantation.

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Fig. 8. Therapeutic effects of the transplantation of hiPSC-EPO–producing cells on renal anemia in adenine-treated mice. Therapeutic effects of the transplantation of hiPSC-EPO–producing cells on renal anemia in adenine-treated mice. Renal anemia was induced using adenine treatment (50 mg/kg body weight daily for 5 weeks) in immunodeficient mice (NOD.CB17-Prkdcscid/J mice). Twenty aggregates of hiPSC-EPO cells (5.0 × 105 cells per aggregate) were transplanted into the kidney subcapsules of mice with renal anemia. (A) Hematocrit was examined during the first 4 weeks after transplantation using glass capillary tubes. (B) Human EPO concentrations in mouse serum at 4 weeks after transplantation were measured using ELISA. (C) Hematocrit was examined for up to 28 weeks after transplantation. The gray shaded areas in (A) and (C) indicate the normal hematocrit range in NOD.CB17-Prkdcscid/J mice. (D) Human EPO concentrations in mouse serum after transplantation were measured using ELISA. (E) The hiPSC-EPO–producing cell grafts were evaluated using immunohistochemistry for EPO (green), AFP (red) and ALBUMIN (red) and using H&E staining. (F) The new vasculature in the grafts derived from host mice was examined by anti-mouse CD31/PECAM-1 immunostaining and H&E staining. (G) The human EPO concentrations in host mouse serum after phlebotomy were measured using ELISA. The data from three independent experiments are means ± SEM; n = 6 for hiPSC-EPO–producing cells and saline in (A) and (B). The data from two independent experiments are means ± SEM; n = 4 for hiPSC-EPO cells and saline in (C), (D), and (G). *P < 0.05 versus control; ANOVA with Bonferroni’s test (A, C, D, and G) and Student’s t test (B). Scale bars, 40 μm (E) and 20 μm (F). Hirofumi Hitomi et al., Sci Transl Med 2017;9:eaaj2300 Published by AAAS