The Impact of Potential Islet Precursor Cells on Islet Autotransplantation Outcomes

Abstract

Islet autotransplant patients represent excellent subjects to assess the posttransplant impact of islet precursors, as chronic pancreatitis (CP) causes an elevation of ductal cells, pancreatic precursors cells, and hormone-positive acinar cells. The relationship between these cell types and autograft outcomes should be more apparent than would be the case in the context of an allograft program with confounding immunological variables. To improve diabetic control following total pancreatectomy for CP, nonpurified islets were autotransplanted into the liver. Pancreas specimens were recovered from 23 patients and stained for antigens including: insulin, glucagon, cytokeratin 19, cytokeratin 7, and PDX-1. In line with previous reports, the prevalence of ductal cells, non-islet endocrine cells and non-islet PDX-1-expressing cells was significantly higher in CP glands compared with normal pancreata. When correlating follow-up data (i.e., fasting and stimulated C-peptide/glucose levels and HbA1c%) with pancreas immunoreactivity, high levels of ductal cells, non-islet PDX-1-positive cells, and non-islet glucagon-positive cells were associated with superior outcomes, detectable up to 2 years posttransplant. To conclude, the acinar parenchyma and ductal epithelium of the CP pancreas show an upregulation of both endocrine and pre-endocrine cell types, which appear to have a positive effect on islet graft outcomes in autotransplantation setting.