epidermal-growth-factor and Brain-Diseases

To evaluate neural stem/progenitor cell (NPC) transplantation therapy in cat models of neurodegenerative diseases, we have isolated, expanded and characterized feline NPCs (fNPCs) from normal fetal cat brain. Feline NPCs responsive to both human epidermal growth factor (hEGF) and human fibroblast growth factor 2 (hFGF2) proliferated as neurospheres, which were able to differentiate to neurons and glial cells. The analysis of growth factors indicated that both hEGF and hFGF2 were required for proliferation of fNPCs. In contrast to the effect on human NPCs, human leukemia inhibitory factor (hLIF) enhanced differentiation of fNPCs. Expanded fNPCs were injected into the brains of normal adult cats. Immunohistochemical analysis showed that the majority of transplanted cells were located adjacent to the injection site and some fNPCs differentiated into neurons. The survival of transplanted fNPCs over time was monitored using non-invasive bioluminescent imaging technology. This study provided the first evidence of allotransplantation of fNPCs into feline CNS. Cats have heterogeneous genetic backgrounds and possess neurological diseases that closely resemble analogous human diseases. The characterization of fNPCs and exploration of non-invasive bioluminescent imaging to track transplanted cells in this study will allow evaluation of NPC transplantation therapy using feline models of human neurological diseases.

Topics: Animals; Biomarkers; Brain; Brain Diseases; Brain Tissue Transplantation; Cell Differentiation; Cell Proliferation; Cell Separation; Cell Survival; Cells, Cultured; Epidermal Growth Factor; Fibroblast Growth Factor 2; Graft Survival; Humans; Leukemia Inhibitory Factor; Luminescent Proteins; Models, Animal; Nerve Tissue Proteins; Neuroglia; Neurons; Stem Cell Transplantation; Stem Cells

Recent development in stem cell biology has indicated a new possible approach for the treatment of neurological diseases. However, in spite of tremendous hope generated, we are still on the way to understand if the use of stem cells to repair mature brain and spinal cord is a reliable possibility. In particular, we know very little on the in situ regulation of adult neural stem, and this also negatively impact on cell transplant possibilities. In this chapter we will discuss issues concerning the role and function of stem cells in neurological diseases, with regard to the impact of features of degenerating neurons and glial cells on in situ stem cells. Stem cell location and biology in the adult brain, brain host reaction to transplantation, neural stem cell reaction to experimental injuries and possibilities for exogenous regulation are the main topics discussed.

Topics: 2',3'-Cyclic-Nucleotide Phosphodiesterases; Animals; Bisbenzimidazole; Blotting, Western; Brain; Brain Diseases; Cell Differentiation; Cell Division; Cells, Cultured; Cerebral Ventricle Neoplasms; Encephalomyelitis, Autoimmune, Experimental; Epidermal Growth Factor; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; In Vitro Techniques; Injections, Intraventricular; Intermediate Filament Proteins; Male; Microscopy, Confocal; Neoplasms; Nerve Degeneration; Nerve Growth Factor; Nerve Tissue Proteins; Nestin; Neural Cell Adhesion Molecule L1; Neuroglia; Neurons; Rats; Sialic Acids; Stem Cell Transplantation; Stem Cells; Wound Healing

Since EGF is known to protect and stimulate the activity of dopaminergic neurons, an autoradiographic study of [125I]EGF binding sites was performed in the striatum and pallidal complex in parkinsonian syndromes. The analysis was performed on postmortem brain tissues of three control subjects, three patients with Parkinson's disease, and three patients with progressive supranuclear palsy, another parkinsonian syndrome in which dopaminergic neurons also degenerate. Since all six patients had been treated with L-Dopa, we also analyzed the effects of this drug in an animal model of Parkinson's disease. Quantitative analysis of [125I]EGF binding was performed on the brains of three control monkeys, nine monkeys rendered parkinsonian by MPTP intoxication, three of which were treated with L-Dopa. An increased density of [125I]EGF binding was observed at anterior levels in the dorsal striatum, but not in the pallidum, of patients with Parkinson's disease and progressive supranuclear palsy. [125I]EGF binding was unchanged in parkinsonian monkeys whether or not they had been treated with L-Dopa. The data suggest an increased expression of EGFRs in the striatum in chronic parkinsonian syndromes but not in acute models of the disease.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Aged; Aged, 80 and over; Animals; Basal Ganglia; Brain Diseases; Dopamine Agents; Epidermal Growth Factor; ErbB Receptors; Female; Humans; Immunohistochemistry; Iodine Radioisotopes; Macaca fascicularis; Male; Parkinson Disease; Supranuclear Palsy, Progressive; Tetrabenazine