Morphologic Evidence of Interactions Between Adult Ductal Epithelium of Pancreas and Fetal Foregut Mesenchyme

First, tissue recombinants were used to determine the residual capability of adult endodermal pancreatic ductal epithelium to form islets. Second, adult epithelium was challenged by placing it between adult stroma and fetal mesenchyme to investigate the epithelial response (subsequently called challenge grafts). Trypsin was used to isolate adult mouse (heteroplastic) or rat (homoplastic) pancreatic ductal epithelium and fetal rat mesenchyme. All the adult epithelium was maximally stressed with alloxan to control for β-cell contamination. Fetal mesenchyme was layered with epithelium in vitro for at least 48 h. Subsequently, the recombinants were grafted into nude mice and allowed to develop for 4–6 wk. To assess development, grafts were removed and fixed for both light and electron microscopy. In general, the grafts became organized into vesicles, tubules, and buds, many of which were in the form of vascularized isletlike structures. Epithelium responded with mitosis and intercellular adhesion. The range of cytodifferentiation varied. Culture time, age, and adhesiveness of the fetal mesenchyme and the amount of adult epithelium used in making the recombinants influenced the degree of differentiation. Analysis of fine structure of isletlike structures revealed cells with small electron-dense granules. These observations provide evidence for activation of endodermal epithelium taken from an adult mammal.