Multipotentiality, homing properties, and pyramidal neurogenesis of CNS-derived LeX(ssea-1)+/CXCR4+ stem cells.
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.
Corti
Stefania
S
Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation, Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Milan, Italy.
Locatelli
Federica
F
Papadimitriou
Dimitra
D
Donadoni
Chiara
C
Del Bo
Roberto
R
Fortunato
Francesco
F
Strazzer
Sandra
S
Salani
Sabrina
S
Bresolin
Nereo
N
Comi
Giacomo P
GP
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D002469:Cell Separation; D002470:Cell Survival; D002490:Central Nervous System / Q000378:metabolism*; D002633:Chemotaxis; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016256:Lewis X Antigen / Q000235:genetics; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000628:therapy; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D014158:Transcription, Genetic
D000199:Actins; D001426:Bacterial Proteins; D016256:Lewis X Antigen; D008164:Luminescent Proteins; D019718:Receptors, CXCR4; C054562:yellow fluorescent protein, Bacteria; D049452:Green Fluorescent Proteins