Role of pancreatic polypeptide as a market of transplanted insulin-producing fetal pig cells

Transplantation of insulin-producing fetal pancreatic tissue into diabetic recipients has been shown to normalize blood glucose levels after several m onths. This time period is required for the growth and maturation of the fe tal tissue so insulin levels cannot be used as a marker of graft function w hile the p-cell is immature. Therefore, we have examined the use of another pancreatic endocrine hormone, pancreatic polypeptide (PP), to monitor graf t function. The cell that produces this hormone has been shown to be the fi rst mature endocrine cell in the fetal pancreas. Fetal pig pancreatic tissu e, both in the form of 1 mm(3) explants and islet-like cell clusters (ICCs) , was transplanted into immunodeficient SCID mice and the levels of PP and insulin were measured in plasma and in the graft for up to 12 weeks. PP was detected in the untransplanted explants (0.58 pmol/mg) and ICCs (0.06 pmol /ICC) and the PP to insulin ratio was 2.7% and 5.8%, respectively. PP (but not porcine C-peptide, a marker of insulin secretion) was detectable in the plasma of SCID mice from 4 days to 3 weeks after transplantation, but not thereafter. The highest values were obtained at 4 days to 1 week. In the gr afted tissue PP and insulin were present at all time points and the ratio o f PP to insulin was 59%, 87%, 75%, 56%, 7%, 8%, and 7% at 4 days, 1, 2, 3, 6, 9, and 12 weeks, respectively. The decline in PP levels 3 weeks after tr ansplantation was associated with p-cell development in the graft. PP was a lso secreted by fetal pig pancreatic explants transplanted into diabetic NO D/SCID mice, with plasma levels measurable in the first week after the tiss ue was grafted. In immunocompetent BALB/c mice transplanted with the tissue , PP was detectable in plasma for 2 days after transplantation but not at 4 days, when cellular rejection commenced, or thereafter. We conclude that p lasma PP levels can be used as a marker of the viability of fetal porcine p ancreatic tissue in the first 3 weeks after it is transplanted into mice. T hese findings may have relevance to fetal pancreatic tissue transplanted in to humans if suitable techniques can be developed to separate pig from huma n PP.