Street C N, Lakey J R T, Seeberger K, Helms L, Rajotte R V, Shapiro A M J, Korbutt G S
Surgical Medical Research Institute, University of Alberta, Edmonton, Alberta, Canada T6G 2N8.
J Endocrinol. 2004 Feb;180(2):213-25. doi: 10.1677/joe.0.1800213.
The discovery of a pancreatic adult stem cell would have significant implications for cell-based replacement therapies for type 1 diabetes mellitus. Nestin, a marker for neural precursor cells, has been suggested as a possible marker for islet progenitor cells. We have characterized the expression and localization of nestin in both the intact human pancreas and clinical human pancreatic islet grafts. Nestin was found to be expressed at different levels in the acinar component of human pancreatic biopsies depending on donor, as well as in ductal structures and islets to some degree. In islets, insulin-producing beta-cells rarely co-expressed the protein, and in the ducts a small percentage (1-2%) of cells co-expressed nestin and cytokeratin 19 (CK19) while most expressed only CK19 (90%) or nestin (5-10%) alone. Assessment of nestin expression in neonatal pancreatic sections revealed an increased number of islet-associated positive cells as compared with adult islets. Nestin immunoreactivity was also found in cells of the pancreatic vasculature and mesenchyme as evidenced by co-localization with smooth muscle actin and vimentin. Samples from post-islet isolation clinical islet grafts revealed a pronounced heterogeneity in the proportion of nestin-positive cells (<1-72%). Co-localization studies in these grafts showed that nestin is not co-expressed in endocrine cells and rarely (<5%) with cytokeratin-positive ductal cells. However, relatively high levels of co-expression were found with acinar cells and cells expressing the mesenchymal marker vimentin. In conclusion we have shown a diffuse and variable expression of nestin in human pancreas that may be due to a number of different processes, including post-mortem tissue remodeling and cellular differentiation. For this reason nestin may not be a suitable marker solely for the identification of endocrine precursor cells in the pancreas.
胰腺成体干细胞的发现对于1型糖尿病基于细胞的替代疗法具有重大意义。巢蛋白是神经前体细胞的标志物，有人提出它可能是胰岛祖细胞的标志物。我们已经对巢蛋白在完整的人胰腺和临床人胰岛移植组织中的表达及定位进行了特征分析。研究发现，根据供体不同，巢蛋白在人胰腺活检组织的腺泡成分中表达水平各异，在导管结构和胰岛中也有一定程度的表达。在胰岛中，产生胰岛素的β细胞很少共表达该蛋白，在导管中，一小部分细胞（1 - 2%）同时表达巢蛋白和细胞角蛋白19（CK19），而大多数细胞仅单独表达CK19（90%）或巢蛋白（5 - 10%）。对新生儿胰腺切片中巢蛋白表达的评估显示，与成人胰岛相比，胰岛相关阳性细胞数量增加。胰腺血管和间充质细胞中也发现了巢蛋白免疫反应性，这通过与平滑肌肌动蛋白和波形蛋白的共定位得以证实。胰岛分离后临床胰岛移植组织样本显示，巢蛋白阳性细胞比例存在显著异质性（<1 - 72%）。这些移植组织中的共定位研究表明，巢蛋白在内分泌细胞中不共表达，与细胞角蛋白阳性导管细胞的共表达也很少（<5%）。然而，在腺泡细胞和表达间充质标志物波形蛋白的细胞中发现了相对较高水平的共表达。总之，我们已经证明巢蛋白在人胰腺中呈弥漫性和可变表达，这可能是由于多种不同过程导致的，包括死后组织重塑和细胞分化。因此，巢蛋白可能并非仅适用于识别胰腺中的内分泌前体细胞的标志物。
