Identification and application of pancreatic internal and external progenitor cell having differentiation potency to β-cells

角化细胞生长因子（Keratinocyte growth factor， KGF）是FGF家族中的一员，参与调节细胞生长、分化、粘附、迁移和组织形态发生。此外，据报道，FGF和受体FGFR有助于胰腺的发育。KGF的特异性受体KGFR/FGFR2-IIIb也被认为是胰腺发育早期的一个重要分子。我们专注于KGF和KGFR/FGFR2-IIIb的表达，应用胰腺切除术模型和大鼠急性l -精氨酸-胰腺炎模型来观察成年胰腺的再生。我们试图进一步鉴定胰腺祖细胞对再生内分泌和外分泌细胞有贡献。大鼠胰腺切除术模型1)胰腺腺泡细胞、胰岛排泄导管细胞和内分泌细胞中可见大量Ki67阳性细胞。Ki67阳性细胞数量在胰腺切除术后第3天显著增加，在胰腺切除术后第7天逐渐减少。2)胰腺切除术组与对照组相比，PDX-1阳性细胞数量也明显增多。这表明胰切除术后PDX-1的表达增加。3) KGFR在胰岛α-细胞中表达，提示KGF参与了胰岛α-细胞的功能分化。l -精氨酸诱导胰腺炎1)注射后6 h胰腺间质水肿，注射后第4 d胰腺严重坏死。2)胰腺也有新生血管和导管-导管增生。3)免疫组化分析显示，腺泡细胞和毛细血管内皮细胞中Ki-67标记升高。4)抗巢蛋白抗体免疫印迹显示，注射l -精氨酸后巢蛋白表达增加。在对照大鼠胰腺，部分胰岛毛细血管内皮细胞检测到巢蛋白免疫反应性。5)注射l -精氨酸后，nestin在增殖的毛细血管内皮细胞、导管结构周围的星状细胞和间皮下细胞中表达。结论：在l -精氨酸诱导的胰腺炎恢复后的增殖阶段，特定类型的细胞中出现了短暂的巢蛋白表达，可能代表了干细胞和/或祖细胞对胰腺再生能力的贡献。少

Keratinocyte growth factor, KGF, is a member of FGF families that has been known to participate in regulation of cell growth, differentiation, adhesion, migration and the tissue morphogenesis. Furthermore, it is reported that FGF and the receptor FGFR contribute to the development of the pancreas. The specific receptor of KGF, KGFR/FGFR2-IIIb, is also suggested to be an important molecule in the early period of pancreatic development. We, having focused on the expression of KGF and KGFR/FGFR2-IIIb, applied both the pancreatectomy model and the acute L-arginine-pancreatitis model of the rat to scrutinize regeneration of the adult pancreas. We tried further to identify the pancreatic progenitor cells that contribute to regenerate endocrine and exocrine cells.A. Rat pancreatectomy model1) Many Ki67 positive cells were observed in pancreatic acinar cells, excretory ductal cells and endocrine cells of the islet. The number of Ki67 positive cells increased significantly in 3 days after pancr … More eatectomy and decreased gradually in seven days after the pancreatectomy. 2) The PDX-1 positive cells also were observed in significantly large numbers in pancreatectomy group in comparison with control group. This suggests that expression of PDX-1 increases after pancreatectomy. 3) KGFR was expressed in α-cells of the pancreatic islets implying that KGF contributes to the functional differentiation of the α-cells.B. L-arginine-induced pancreatitis1) Six hours after L-arginine injection, interstitial edema was observed in the pancreas, whereas on day 4 postinjection, there was severe pancreatic necrosis. 2) Neovascularization and ductal-ductular proliferation were also present in the pancreas. 3) Immunohistochemical analysis revealed increased Ki-67 labeling in acinar cells and capillary endothelial cells. 4) Immunoblotting using anti-nestin antibody revealed increased nestin expression after L-arginine injection. In the control rat pancreas, nestin immunoreactivity was detected in a few capillary endothelial cells in some islets. 5) After L-arginine injection, nestin was expressed in proliferating capillary endothelial cells, in stellate cells surrounding ductular structures and in submesothelial cells. Conclusions : Transient nestin expression occurs in specific cell types during the proliferative stage after recovery from L-arginine-induced pancreatitis and may represent the contribution of stem cells and/or progenitor cells to the regenerative capacity of the pancreas. Less