Astroglial differentiation of fibronectin‑positive human "glia-like" cells.

Abstract

Fibronectin (Fn) is a glycoprotein of extracellular matrix produced by a variety of mesenchymal and neoplastic cell types. In adult brain tissue, Fn is restricted to blood vessels. However, adult human brain cultures are almost entirely comprised of flat or spindle‑shaped Fn-positive cells usually referred to as "glia-like" cells. Since Fn is primarily present in fibroblasts, these cultures may be considered to be of non-glial origin. Cells gained by long-term culturing of adult human brain tissue derived from brain biopsies obtained from 12 patients with non-malignant diagnoses were examined by immunofluorescence methods. Primary cultures contained GFAP-/Vim+/Fn+ "glia-like" cells (95-98 %) and GFAP+/Vim+/Fn- astrocytes (0.1 %) which disappeared by passage number 3. The formation of cell processes and enlargement of cell bodies was observed in 9 of 12 cultures with decreased cell growth during passages 12 to 17. It is remarkable that during this period, all "glia-like" cells became GFAP+/Vim+/Fn+. Herein, we confirm our previously published hypothesis about the origin of adult human "glia-like" cells, which we consider to be precursor cells scattered through the brain cortex and subcortical white matter. Cultures were comprised entirely of GFAP-/Fn+ "glia-like" cells and showed morphological and immunochemical astroglial differentiation with spontaneously decelerated growth during prolonged passaging. We propose that the adult human brain tissue contains a "dormant population" of undefined glial precursor cells. Under culture, these cells show to have a high proliferative capacity and different stages of cell dedifferentiation (Fig. 2, Ref. 21).