Multipotentiality, homing properties, and pyramidal neurogenesis of CNS‐derived LeX(ssea‐1) + /CXCR4 + stem cells

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Abstract
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.
Funding Information
  • Ministero dell’Istruzione, dell’Università e della Ricerca