Figure 6. Transplanted cPB cells remain functional and protect mice from chemically induced diabetes.

(a) Schematic representation of the transplantation of cPB into immunodeficient mice. (b) ELISA analysis of serum from fasted and glucose-challenged mice 2 months post transplantation with either fibroblasts (Fib) or cPB are shown. cPB graft-bearing mice exhibit significant higher levels of circulating human C-peptide in serum after a glucose bolus, indicating that transplanted cPB cells remain functional in vivo. Mice transplanted with Fib controls do not exhibit circulating human C-peptide. n=12 mice for cPB and n=5 mice for Fib. P value was calculated using a two-tailed Student's t-test. (c) Immunofluorescence analysis of 2-month-old cPB cell grafts shows co-expression of C-peptide (C-pep) and the beta-cell transcription factors PDX1 and NKX6.1 but not the hormones glucagon (GCG) and somatostatin (SST). Scale bar, 50 μm. Data shown are representative of two mice. (d) Fed blood glucose levels of mice-bearing cPB grafts with circulating human C-peptide levels above 200 pM after glucose stimulation and control fibroblasts are shown. Mice were treated with the mouse-specific beta-cell toxin streptozotocine (STZ) to ablate endogenous beta cells. Uni-lateral nephrectomy of cPB graft-bearing mice 5 weeks after STZ treatment resulted in a rapid rise in blood glucose levels, directly demonstrating euglycemic control due to cPB grafts after STZ treatment in these mice. n=6 mice for cPB and n=6 mice for Fib. P value was calculated using a two-tailed Student's t-test. *P<0.05.