Salivary gland progenitor cells induced by duct ligation differentiate into hepatic and pancreatic lineages
Salivary gland progenitor cells induced by duct ligation differentiate into hepatic and pancreatic lineages
复制标题
DOI：
10.1053/jhep.2003.50259
复制
发表时间：
2003-07-01
期刊：
影响因子：
13.5
通讯作者：
Endo, F
中科院分区：
文献类型：
--
作者：
Okumura, K;Nakamura, K;Endo, F
组织损伤可以基于再生反应（包括祖细胞增殖）来评估。在唾液腺中，由主导管结扎引起的组织损伤导致腺泡细胞的消失和导管细胞的显著增殖。导管的重新开放导致腺泡细胞在1至2周内重新增殖，这表明组织祖细胞在受损状态下活化。由于下颌下腺来源于内胚层和外胚层，我们研究了内胚层祖细胞存在的可能性。我们培养从结扎的唾液腺获得的细胞，并鉴定上皮样细胞集落。我们通过有限稀释法挑选并纯化细胞，并将其中一个命名为SGP-1的细胞用于进一步的实验。SGP-1表达α 6 β 1整联蛋白和细胞质层粘连蛋白。造血干细胞标志物CD 34和肝卵圆细胞标志物如白蛋白、甲胎蛋白（AFP）和细胞角蛋白19均为A阴性。然而，当SGP-1细胞通过门静脉移植到肝脏中时，这些细胞整合到肝小梁中并产生白蛋白。当SGP-1细胞在I型胶原包被的培养皿上形成簇时，它们分化成内胚层谱系，并且出现2种主要类型的簇：一种含有AFP和/或白蛋白阳性的细胞（肝簇），另一种含有胰高血糖素和/或胰岛素阳性的细胞（胰簇）。在层粘连蛋白包被的培养皿上，SGP-1选择性地分化为肝型细胞。结论：从大鼠唾液腺中分离的多能祖细胞具有组织干细胞的特性，并能分化为内胚层细胞。
Tissue damage can be assessed based on regenerative responses, including progenitor cell proliferation. In the salivary gland, tissue damage induced by ligation of main ducts leads to the disappearance of acinar cells and to marked proliferation of ductal cells. Reopening of the ducts leads to repopulation of acinar cells within I to 2 weeks, which suggests activation of tissue progenitor cells in a damaged state. Because submandibular glands derive from the endoderm and ectoderm, we investigated the possibility of the presence of endodermal progenitor cells. We cultured cells obtained from the ligated salivary gland and identified colonies of epithelium-like cells. We singled out and purified the cells by limited dilution, and one of the cells designated SGP-1 was used for further experiments. The SGP-1 expresses both alpha6beta1 integrin and cytoplasmic laminin. The hematopoietic stem cell marker CD34 and hepatic oval cell markers such as albumin, a-fetoprotein (AFP), and cytokeratin 19 are A negative. However, when SGP-1 cells were transplanted into the liver via the portal vein, these cells were integrated into hepatic trabecula and produced albumin. When SGP-1 cells formed dusters on type I collagen-coated dishes, they differentiated into endodermal lineage and 2 major types of dusters appeared: one contained cells positive for AFP and/or albumin (hepatic cluster) and the other positive for glucagon and/or insulin (pancreatic duster). On laminin-coated dishes, SGP-1 selectively differentiated into hepatic-type cells. In conclusion, the multipotent progenitor cells isolated from the rat salivary gland have characteristics of tissue stem cells and can differentiate into cells of endodermal lineages.