Neurotrophins such as nerve growth factor (NGF) were initially considered to be the major neurotrophic factors. Recently, however, other growth factors have also been identified as being involved in neuronal differentiation; these include epidermal growth factor (EGF), fibroblast growth factor (FGF), insulin-like growth factor (IGF) and cytokines. Among these recently discovered growth factors, two major cytokine superfamilies, the transforming growth factor-β (TGF-β) and the hemopoietins, have been found to mediate an extensive range of developmental event in the nervous system that often rivals and freauentlv exceeds that of the classic neurotrophins. Bone marrow stromal cells, which produce lots of cytokines, have been shown to support the growth and differentiation of neuroblastoma...[ Read more ]

Neurotrophins such as nerve growth factor (NGF) were initially considered to be the major neurotrophic factors. Recently, however, other growth factors have also been identified as being involved in neuronal differentiation; these include epidermal growth factor (EGF), fibroblast growth factor (FGF), insulin-like growth factor (IGF) and cytokines. Among these recently discovered growth factors, two major cytokine superfamilies, the transforming growth factor-β (TGF-β) and the hemopoietins, have been found to mediate an extensive range of developmental event in the nervous system that often rivals and freauentlv exceeds that of the classic neurotrophins. Bone marrow stromal cells, which produce lots of cytokines, have been shown to support the growth and differentiation of neuroblastoma cells. Thus, in order to study the effects of bone marrow stromal cells on neuronal differentiation, we have co-cultured neuroblastoma X glioma hybrid NG108-15 cells with human bone marrow stromal cells. After co-culturing, clones were isolated exhibiting morphologically differentiated phenotypes and high levels of neurofilament expression. Interestingly, these clones maintain their ability to proliferate in contrast to differentiated NG108-15 cells induced by dibutyryladenosine 3':5'-cyclic monophosphate (Bt₂-cAMP). The effect of human bone marrow stromal cells was further studied on a human neuroblastoma cell line, IMR-32. Both co-culturing with stromal cells and treatment with stromal cellular extract can induce the differentiation of IMR-32 cells. Moreover, this study demonstrated that the factor in stromal cellular extract responsible for IMR-32 cells differentiation might be of protein nature. Thus, the finding that bone marrow stromal cells can induce the differentiation of NG108-15 cells and IMR-32 cells, indicates that these cells might be a possible source for screening of novel neurotrophic factors.