epidermal-growth-factor and Central-Nervous-System-Diseases

We found the expression of neurofilament was very low in undifferentiated human adult bone marrow mesenchymal stem cells (hMSCs), but its expression could be significantly induced after treatment with combination of growth factors. Approximately 16% of hMSCs differentiated into cells expressing neurofilament after treatment with a combination of FGF and RA, retinoic acid. We also examined the effect of five different cell culture substrates on the expression of neurofilament. One specific combination that was particularly effective in provoking pre-neuronal differentiation was culturing hMSCs on fibronectin-coated dishes and stimulating them with FGF and RA; 40% of cells expressed neurofilament. These results suggest that growth factors and substrates, in combination, can effectively initiate differentiation of hMSCs along a neuronal pathway.

Topics: Adult; Bone Marrow Cells; Bone Marrow Transplantation; Cell Culture Techniques; Cell Differentiation; Cell Division; Cell Lineage; Cell Size; Cells, Cultured; Central Nervous System Diseases; Colforsin; Culture Media; Cyclic AMP; Drug Combinations; Epidermal Growth Factor; Fibroblast Growth Factors; Fibronectins; Growth Substances; Humans; Male; Mesoderm; Neurofilament Proteins; Neurons; RNA, Messenger; Stem Cells; Thionucleotides; Tretinoin

Human epidermal growth factor (gEGF), a potent stimulator of the growth of many tissues in culture, has been isolated from human urine and subsequently identified in many human biological fluids. We have partially purified and characterized hEGF-like substance(s) from human cerebrospinal fluid (CSF) and determined the concentrations of immunoreactive (IR) hEGF in CSF obtained from patients with a variety of neurological diseases. Competitive binding curves generated by the CSF samples appeared to be parallel to standard hEGF both in RIA and radioreceptor assays using human placental membrane. Sephadex G-50 gel exclusion chromatography of the CSF extract revealed a single peak of IR-hEGF which coeluted with standard hEGF. The apparent mol wt of the CSF hEGF-like substances(s) was estimated to be 8000 by sodium dodecyl sulfate poplyacrylamide gel electrophoresis, and its approximate pI was 4.5 as determined by isoelectric focusing. The concentrations of IR-hEGF in CSF from patients with pituitary and brain tumors and radiculomyelopathy were significantly higher than those from control subjects, while neither patients with hydrocephalus nor encephalomeningitis had CSF IR-hEGF levels statistically different from the control subjects. The presence of hEGF-like substance(s) in human CSF suggests that it may play an important physiological role in the function of the human nervous tissues but does not provide any evidence of its source.

Topics: Adolescent; Adult; Aged; Binding, Competitive; Central Nervous System Diseases; Child; Child, Preschool; Chromatography, Gel; Electrophoresis, Polyacrylamide Gel; Epidermal Growth Factor; Female; Humans; Infant; Isoelectric Focusing; Male; Middle Aged; Radioimmunoassay; Radioligand Assay