Exosomes Secreted by Umbilical Cord Blood-Derived Mesenchymal Stem Cell Attenuate Diabetes in Mice

Figure 4

Timeline of the in vivo experimental design. Schematic illustration of the experimental plan. (a) In brief, 8-week-old adult male C57BL/6 mice (body weight~20 g) were used throughout the study. To induce diabetes, mice were injected with multiple low-dose injections of streptozotocin intraperitoneal (i.p.) (STZ; 40 mg/kg freshly dissolved in 0.1 mmol/l sodium citrate (pH 4.5)) for 5 consecutive days. Blood samples were collected from tail-vein and were used to monitor glucose levels. Animals were considered diabetic when their blood glucose levels were ≥200 mg/dl. Mice in the nondiabetic control group received a corresponding volume of sodium citrate buffer alone. On day 10, after STZ treatment, mice were randomly divided into three groups: (i) STZ+PBS group that received i.v. injection of PBS (), (ii) STZ+MSC group that received i.v. injection of UCB-MSC cells/mice (), and (iii) STZ+MSC-Exo group that received i.v. injection of exosomes derived from MSCs/mice from day 11 to day 17 (). To explore the homeostatic turnover of pancreatic cells, two doses of 50 μg/kg BrdU (at 2 h and 16 h) were administered at day 18 (three mice for each group). At day 18, mice were sacrificed and processed biochemical and molecular analysis.