Arch Hellen Med, 28(1), January-February 2011, 89-102
Complete regeneration of the pancreas including islets of Langerhans,
OBJECTIVE Elucidation of in vivo systems for complete pancreatic regeneration in animal models.
METHOD Using only syngeneic Lewis rats, whole liver, bone marrow (BM) with bone, BM clot, or nonparenchymal liver tissue was transplanted into the host pancreas. In addition, either insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibody (mAb) or vascular endothelial growth factor (VEGF) Ab was injected into the host spleen. The experimental rats were followed for 5.5−6 months. Insulin-like growth factor binding protein 2 (IGFBP2) was examined in hematopoietic mononuclear cells (MNC) and pancreatic cells using flow cytometry (FCM). Electron microscopic analyses were applied for the embryological studies of regenerated pancreas.
RESULTS Complete pancreatic regeneration, including both the endocrine and exocrine cells, was confirmed in 2 (50%) of 4 females receiving BM clot grafts and VEGF Ab, in 1 (17%) of 6 males receiving whole liver grafts and IGF-1R mAb, and in 3 (60%) of 5 males receiving nonparenchymal liver grafts and VEGF Ab. On FCM, weakly-positive IGFBP2 cells were increased due to rebound activation of injected IGF-1R mAb. IGFBP2 was also expressed in islet β-cells. Islet progenitor cells smaller than erythrocytes regenerated in blood vessels and developed outside of the vessels. Centro-acinar progenitor cells smaller than erythrocytes regenerated in a microcapillary, the walls of which were destroyed after the full development. Acinar cells proliferated through the mitosis of mature cells outside of blood vessels.
CONCLUSIONS Nonparenchymal liver and BM clot grafts produced identical results of pancreatic regeneration. It was concluded that epiblast/germ line-derived host BM cells were mobilized to the grafts, resulting in complete pancreatic regeneration.
Key words: Complete pancreatic regeneration, Insulin-like growth factor binding protein 2, Insulin-like growth factor-1 receptor, Nonparenchymal liver graft, Vascular endothelial growth factor.