Tissue Culture Studies of Schwann Cell Proliferation and Differentiation

Abstract

Neonatal rat sciatic nerve Schwann cells in monolayer culture are stimulated to proliferate and to express a lipid and a protein characteristic of myelin by agents which raise intracellular cyclic adenosine 3'',5''-monophosphate. Both glial growth factor and axolemmal fragments increase the rate of mitosis of cultured rat and human Schwann cells. Rat Schwann cell mitosis is enhanced by a soluble factor produced by concanavalin A-stimulated blood mononuclear cells and inhibited by lead salts. Schwann-like cells cultured from human dermal and plexiform neurofibromas resemble normal human Schwann cells in phenotype and response to mitogens.

Neurofibromin, the Neurofibromatosis Type 1 Ras‐GAP, Is Required for Appropriate P0 Expression and Myelination

“…Expression of activated Ras increased P 0 expression in a Schwann cell line, 9,32 and we have shown here that expression of oncogenic Ras in primary Schwann cells also upregulates P 0 expression. In normal Schwann cells, increasing intracellular cAMP augments Schwann cell differentiation 25,26,33–35 as assessed by increased P 0 expression. Activation of protein kinase A by cAMP inhibits the Ras pathway at the level of Raf activation in some cell types.…”

Nerve growth factor receptors on cultured rat Schwann cells

“…of development (Asbury, 1967), as well as during injury or disease (Thomas, 1948;Asbury and Amason, 1968). In tissue culture, Schwann cells from different regions and different species proliferate in response to mitogens in a uniform manner (Pleasure et al, 1985). In contrast to their PNS counterparts, cultured rat astrocytes contained no detectable NGF binding sites (Table 1).…”

Non‐antagonistic relationship between mitogenic factors and cAMP in adult Schwann cell re‐differentiation

“…Schwann cells (SCs) are a unique cell type in their capacity to respond to cyclic adenosine monophosphate (cAMP) because elevation of intracellular cAMP levels both enhances the rate of G1-S progression stimulated by polypeptide growth factors (Raff et al, 1978a,b) and induces MG expression (Pleasure et al, 1985), therefore mimicking the action of axonal signals (Jessen et al, 1991). Thus, with regard to proliferation, cAMP-stimulating agents synergistically increase the mitogenic potency of neuregulin (Dong et al, 1997; Monje et al, 2006; Rahmatullah et al, 1998; Salzer and Bunge, 1980), and also that of platelet-derived growth factor, PDGF (Davis and Stroobant, 1990; Kim et al, 2001), basic fibroblast growth factor-2, FGF-2 (Dong et al, 1997), insulin, insulin-like growth factor-1, IGF-1 (Stewart et al, 1996) and transforming growth factor-β, TGF-β (Ridley et al, 1989; Stewart et al, 1991).…”