Astrocyte proliferation is strictly controlled during development and in the adult nervous system. In this Study, we examined the role of sulfated hyaluronan (SHya) in the proliferation and differentiation of normal human astrocytes (NHAs). Cells were Cultured with different concentrations of SHya for 7 days, and the number of viable cells and the presence Of neural cell-specific genes were determined to assess their proliferation and development, respectively. With SHya, cell proliferation increased non-significantly. Furthermore, remarkable enhancing action by SHya on connexin-26, -32, and -43 gene expressions were observed during the culture of NHAs. It has been Suggested that a fraction of NHAs have neural precursor activity that gives rise to astrocytes themselves, oligodendrocytes, and neurons, Our results clearly demonstrated that the e expression of specific genes for neural precursor cells, astrocytes, neurons, and oligodendrocytes was significantly increased to 50 mu g/mL in SHya-treated Cultures when compared with that of the control culture. These findings Suggest that SHya plays an important role in the proliferation and differentiation of NHAs and in the production of a novel material for tissue engineering. (C) 2008 Wiley Periodicals, Inc. J Biomed Mater Res 90A: 713-719, 2009