Differentiation of patient-specific induced pluripotent stem cells derived from type 1 diabetes peripheral blood mononuclear cells into pancreatic β-like cells

Figure 4 Regulation of hyperglycemia by type 1 diabetes-β-like cells in diabetic mice. A: Schematic of renal subcapsular transplantation. Schematic representation of the process involved in subcapsular kidney transplantation of type 1 diabetes (T1D)-β-like cells aimed at regulating blood glucose levels in streptozotocin-induced diabetic mice; B: Longitudinal body weight monitoring. Body weight measurements in streptozotocin-induced diabetic mice demonstrated a gradual decline starting from the onset of the experiment, continuing throughout the entire 30-day duration until study completion (n = 15, 18.90 ± 0.40 vs 22.9 ± 0.89, ^aP < 0.01); C: Random blood glucose profiles. Random blood glucose assessments in the tail vein of mice from each diabetic group (n = 5 samples per group) showed that following transplantation of T1D-β-like cells under the renal capsule (performed on day 10 post-modeling), blood glucose levels in the M3C and M3C + triiodothyronine (T3) + vitamin C (Vc) groups decreased significantly over 2 days, compared to the control (21.16 ± 2.13 vs 26.8 ± 2.51; 20.3 ± 1.50 vs 26.8 ± 2.51; ^aP < 0.01, ^bP < 0.01, M3C and M3C + T3 + Vc group compared with the control group, respectively). However, glucose levels rose again and stabilized at high levels, with no statistically significant differences relative to the control group; D: Flow cytometry analysis of grafted cells. Flow cytometry results indicated an increase in the percentages of insulin⁺ (0.5%, 0.7%) and mCherry⁺ (3.8%, 4.5%) cells compared to isotype-negative controls 20 days post-transplantation, though no significant difference was noted between the M3C and M3C + T3 + Vc groups; E: Intraperitoneal glucose tolerance test. Intraperitoneal glucose tolerance test (n = 5 samples per group), M3C and M3C + T3 + Vc groups initially registered high blood glucose levels which peaked at 15 minutes, subsequently decreasing at the 60^th and 90^th minutes. In contrast, blood glucose in the control group began to decrease post 15 minutes, but no significant differences were observed between the M3C and M3C + T3 + Vc groups; F: Insulin tolerance test in transplanted mice. Insulin tolerance test (n = 5 samples per group), post-intraperitoneal insulin injections, blood glucose levels in the tails of M3C and M3C + T3 + Vc mice reached their lowest at the 30-minute mark before rising again. This pattern was consistent in the control group, where levels also decreased after 15 minutes, with no significant differences between the M3C and M3C + T3 + Vc groups. T1D: Type 1 diabetes; STZ: Streptozotocin; T3: Triiodothyronine; Vc: Vitamin C.