Heterogeneous expression of nestin in myofibroblasts of various human tissues

In this study we explored the distribution of nestin-positive cells in extraneural human tissues with special reference to stromal myofibroblasts. Tissue microarrays were constructed from various tissues with normal histology and tissues with fibrosing disorders. Sections were immunostained for nestin, alpha-smooth muscle actin (alpha-SMA), desmin, vimentin, CD34, and other stromal markers. Nestin was expressed in the myoepithelium of the breast, podocytes of the renal glomerulus, and endothelial cells of most organs. Nestin was also expressed in the stroma of several organs, including the intestine, uterine cervix, and endometrium. Nestin-positive fibroblast-like cells appeared in the stroma of the kidney, pancreas, lung, and skin in fibrosing conditions. With the notable exception of endometrial stromal cells, most of these nestin-positive stromal cells were alpha-SMA-positive. Interestingly, we observed a concomitant appearance of nestin- and CD34-positive myofibroblasts under fibrosing conditions. Further investigation showed that nestin was expressed by stromal fibroblasts in cervical squamous cell carcinoma, but not in lung adenocarcinoma, pointing to heterogeneity of cancer stroma. In conclusion, nestin was expressed in variable proportions of stromal myofibroblasts in human tissues. The differential expression of nestin may indicate phenotypic and functional heterogeneity. Nestin-positive myofibroblast may represent a relatively immature subpopulation of cells with multipotentiality.