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Platelet-Derived Growth Factor Enables Direct Derivation of Oligodendrocyte Progenitors from CNS Stem Cells

by Rao, Rajesh Chalamalasetty

Abstract (Summary)
Oligodendrocytes derived in the laboratory from stem cells have been proposed as a treatment for acute and chronic injury to the central nervous system (CNS). Platelet-derived growth factor-receptor alpha (PDGFRÑ)w signaling is known to play an important role for regulation of oligodendrocyte progenitor cell numbers both during development and adulthood. Here, we analyze the effect of PDGFRÑ signaling on CNS stem cells derived from embryonic day 13.5 murine cortex and cultured in monolayer. Fetal and adult CNS stem cells express PDGFRÑ, and PDGF-AA treatment increases viability and proliferation of these cells. In the absence of insulin, this effect of PDGF-AA is very clear. Consistent with this result, PDGF-AA strongly stimulates glycolytic rate. PDGF-AA treatment rapidly induces morphological changes in the cells although the cells maintain expression of a wide range of precursor markers. We show that a brief exposure to PDGF-AA rapidly and efficiently induces oligodendrocytes from CNS stem cells. Our data suggest that phosphoinositide kinase-3 (PI3K)/Akt, mitogen-activated protein/extracellular signal-regulated kinase kinase/extracellular signal-related kinase (MEK/Erk), mammalian target of rapamycin (mTOR) regulate survival, proliferation, glycolytic rate, and oligodendrogliogenesis induced by PDGF-AA. By treating with PDGF-AA, progenitor cells directly from embryonic cortex can be expanded and differentiated into oligodendrocytes with high efficiency. Our results show that PDGF-AA promotes oligodendrocyte progenitor generation from CNS stem cells and supports their survival and proliferation. The derivation of oligodendrocytes demonstrated here may support the safe and effective use of stem cells in the development of new therapies targeting this cell type.
Bibliographical Information:

Advisor:Diane Krause

School:Yale University

School Location:USA - Connecticut

Source Type:Master's Thesis

Keywords:receptor platelet derived growth factor alpha receptors injuries central nervous system humans oligodendroglia

ISBN:

Date of Publication:04/09/2008

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