OBJECTIVE: Platelet-derived growth factor (PDGF)-responsive neural precursors (PRPs; also known as oligodendrocyte progenitor cells) are one of the best characterized precursor cell populations of the rodent central nervous system. Yet little is known about the biology of human PRPs because of an apparent inability to culture and expand them in large numbers. This study was designed to establish an approach that allows direct comparisons between the biology of fetal and adult human PRPs, as a means to address potential differences in intrinsic myelin-production capabilities. METHODS: We used the neurosphere culture system, under low plating density, to isolate, culture, and compare the properties of fetal and adult human PRPs. RESULTS: PDGF stimulated fetal human PRPs to generate neurospheres that differentiated primarily into oligodendrocytes, which acquired myelin basic protein expression, as well as neurons and a small number of astrocytes. Together with PDGF, fibroblast growth factor 2 promoted fetal human PRP expansion. In contrast, adult human PRPs isolated from the corpus callosum required twice the culture period to generate neurospheres, which contained oligodendrocytes, as well as astrocytes, but not neurons. Strikingly, fibroblast growth factor 2 did not promote adult human PRP self-renewal. INTERPRETATION: Differences in the intrinsic proliferation, phenotype, and self-renewal properties of fetal and adult human PRPs suggest they are distinct populations, which may result in distinct myelin-production capabilities.
OBJECTIVE: Platelet-derived growth factor (PDGF)-responsive neural precursors (PRPs; also known as oligodendrocyte progenitor cells) are one of the best characterized precursor cell populations of the rodent central nervous system. Yet little is known about the biology of humanPRPs because of an apparent inability to culture and expand them in large numbers. This study was designed to establish an approach that allows direct comparisons between the biology of fetal and adult humanPRPs, as a means to address potential differences in intrinsic myelin-production capabilities. METHODS: We used the neurosphere culture system, under low plating density, to isolate, culture, and compare the properties of fetal and adult humanPRPs. RESULTS: PDGF stimulated fetal humanPRPs to generate neurospheres that differentiated primarily into oligodendrocytes, which acquired myelin basic protein expression, as well as neurons and a small number of astrocytes. Together with PDGF, fibroblast growth factor 2 promoted fetal humanPRP expansion. In contrast, adult humanPRPs isolated from the corpus callosum required twice the culture period to generate neurospheres, which contained oligodendrocytes, as well as astrocytes, but not neurons. Strikingly, fibroblast growth factor 2 did not promote adult humanPRP self-renewal. INTERPRETATION: Differences in the intrinsic proliferation, phenotype, and self-renewal properties of fetal and adult humanPRPs suggest they are distinct populations, which may result in distinct myelin-production capabilities.
Authors: Owen D Stechishin; H Artee Luchman; Yibing Ruan; Michael D Blough; Stephanie A Nguyen; John J Kelly; J Gregory Cairncross; Samuel Weiss Journal: Neuro Oncol Date: 2012-12-21 Impact factor: 12.300