Heterogeneous expression of nestin in myofibroblasts of various human tissues

Abstract

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.

Mesenchymal Stem Cell Therapy Protects Lungs from Radiation-Induced Endothelial Cell Loss by Restoring Superoxide Dismutase 1 Expression

“…In line with our findings, immunofluorescence microscopy already revealed that Nestin is expressed in small proportions of fibroblasts (70). Furthermore, a concomitant appearance of Nestin-and CD34-positive myofibroblasts was observed under fibrosing conditions, suggesting that the differential expression of Nestin may not only indicate phenotypic and functional heterogeneity but may also indicate that Nestinpositive myofibroblast may represent a relatively immature subpopulation of cells with multipotentiality (41).…”

Characterization of nestin expression and vessel association in the ischemic core following focal cerebral ischemia in rats

“…Interestingly, the aforementioned findings and spatiotemporal patterns of nestin-positive cells are analogous to those described for cells derived from the adventitial fibroblasts following brain infarct (Brierley and Brown 1982). In addition, nestin is induced in fibroblast-like cells under fibrotic conditions or after injury in various tissues including heart and kidney (Calderone 2012;Kishaba et al 2010). Our data raise the possibility that these nestin-positive cells are derived from fibroblasts comprising the vascular adventitia of the larger caliber vessels at this later time point, when the capillary bed is actually being destroyed.…”

Human mesenchymal stem cells express neuronal markers after osteogenic and adipogenic differentiation

“…The early neuronal marker III-tubulin, abundantly expressed in the central and peripheral nervous system [16], is also present in non-neural tissues, both in embryonic and adult stages [16,42], in tumor cells [43,44] and as a component of the mitotic spindles of many cell types [45]. Nestin, considered a major neural progenitor marker [46], has also been found in extra-neural tissues [47] and various types of human solid tumors [48], and has been considered a predictor of poor prognosis in patients with malignant melanoma [49]. Similarly, the glial cell markers S100 and GFAP are expressed in a great variety of normal and pathological tissues [50,51].…”