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

角质形成细胞生长因子(KGF)是成纤维细胞生长因子家族的一员，参与调节细胞的生长、分化、黏附、迁移和组织形态发生。此外，有报道称，成纤维细胞生长因子及其受体FGFR参与了胰腺的发育。KGF的特异性受体KGFR/FGFR2-IIIb也被认为是胰腺发育早期的重要分子。在重点研究KGF和KGFFR/FGFR2-IIIb表达的基础上，我们应用大鼠胰腺切除模型和急性L-精氨酸-胰腺炎模型来观察成年胰腺的再生情况。1.大鼠胰腺切除模型1)在胰腺腺泡细胞、排泄性导管细胞和胰岛内分泌细胞中观察到大量Ki67阳性细胞。PANCR…后3d，Ki67阳性细胞数显著增加胰腺切除较多，术后7天逐渐减少。2)胰腺切除组与对照组相比，PDX-1阳性细胞也明显增多。这表明胰腺切除后PDX-1的表达增加。3)胰岛α细胞表达KGFR，提示KGF参与了α细胞的功能分化。B.L精氨酸诱导的胰腺炎1)注射L精氨酸后6h，胰腺间质水肿，注射后4d，胰腺严重坏死。2)胰腺内可见新生血管和导管-导管的增生。3)免疫组织化学显示腺泡细胞和毛细血管内皮细胞Ki-67标记增强。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。在对照组大鼠胰腺中，部分胰岛内的少数毛细血管内皮细胞可见Nestin免疫反应阳性。5)L-精氨酸注射后，巢蛋白表达于增殖中的毛细血管内皮细胞、导管周围的星状细胞和腹膜下皮下细胞。结论：在L精氨酸诱导的胰腺炎模型中，在特定细胞类型的细胞中存在一过性巢蛋白表达，可能代表干细胞和/或前体细胞对胰腺再生能力的贡献。较少

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