Astrocytes promote process outgrowth by adult human oligodendrocytes in vitro through interaction between bFGF and astrocyte extracellular matrix.

Cell-cell interactions regulate many important functions within the central nervous system. In this report, we demonstrate that process outgrowth by adult human oligodendrocytes (OLs) in vitro, an early event of myelinogenesis in vivo, is promoted by astrocytes. To elucidate the mechanisms by which astrocytes might exert this effect, we tested several growth factors known to be produced by astrocytes and found that only basic fibroblast growth factor (bFGF) could enhance process extension by the OL. In correspondence, the treatment of astrocytes with a neutralizing antibody to bFGF decreased their effects in promoting oligodendroglial process outgrowth. The potency of bFGF, however, was only one-third that of astrocytes, and since bFGF did not synergize with other soluble growth factors, we investigated the potential facilitatory role of the extracellular matrix (ECM) deposited by astrocytes. The astrocyte ECM was found to be a promoter of oligodendroglial process extension, and significantly, bFGF synergized with astrocyte ECM to match the potency of live astrocytes. The astrocyte ECM was found in Western blot analyses to contain fibronectin, vitronectin, and laminin. These purified ECM components, as well as heparan sulfate proteoglycan, did not promote oligodendroglial process extension by themselves, although laminin and fibronectin potentiated the effects of bFGF. We conclude that process outgrowth by OLs is guided by astrocytes; the mechanism of the astrocyte effect appears to be due to the combination of bFGF and an unidentified ECM component.