lewis-x-antigen and Neurodegenerative-Diseases

Achieving efficient distribution of neural stem cells throughout the central nervous system (CNS) and robust generation of specific neurons is a major challenge for the development of cell-mediated therapy for neurodegenerative diseases. We isolated a primitive neural stem cell subset, double positive for LeX(Le) and CXCR4(CX) antigens that possesses CNS homing potential and extensive neuronal repopulating capacity. Le+CX+ cells are multipotential and can generate neurons as well as myogenic and endothelial cells. In vivo Le+CX+ cells displayed widespread incorporation and differentiated into cortical and hippocampal pyramidal neurons. Since intravenous delivery could be a less invasive route of transplantation, we investigated whether Le+CX+ cells could migrate across endothelial monolayers. Intracerebral coadministration of SDF enabled migration of intravenously injected Le+CX+ cells into the CNS and a small, yet significant, number of donor cells differentiated into neurons. The isolation of a specific neural stem cell population could offer major advantages to neuronal replacement strategies.

Topics: Actins; Animals; Apoptosis; Bacterial Proteins; Blotting, Western; Brain; Cell Differentiation; Cell Lineage; Cell Movement; Cell Proliferation; Cell Separation; Cell Survival; Central Nervous System; Chemotaxis; Flow Cytometry; Green Fluorescent Proteins; Hematopoietic Stem Cells; Hippocampus; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Lewis X Antigen; Luminescent Proteins; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Models, Biological; Muscle, Skeletal; Neurodegenerative Diseases; Neurons; Phenotype; Receptors, CXCR4; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Stem Cell Transplantation; Stem Cells; Time Factors; Transcription, Genetic