| Abstract No.: | B-D2139 |
| Country: | Canada |
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| Title: | PROMOTING DIFFERENTIATION OF HUMAN FETAL OLIGODENDROCYTE PROGENITORS |
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| Authors/Affiliations: | 2 QiaoLing Cui*; 1 Gabriela Fragoso; 1 Guillermina Almazan; 2 Jack Antel;
1 Department of Pharmacology and Therapeutics; 2 Montreal Neurological Institute, Montreal, QC, Canada
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| Content: | The objective of this study is to identify the factors, which promote differentiation of human fetal oligodendrocyte progenitor cells (OPCs) into mature myelin producing cells. A2B5, a monoclonal antibody that recognizes gangliosides expressed on the surface of OPCs, was used to select OPCs from human fetal brain cells. We observed that (1) a combination of factors PDGF, FGF, IGF-I, T3 and BDNF, used to promote oligodendrocyte differentiation in rodent systems, promotes human A2B5-selected OPC to differentiate into myelin basic protein-expressing oligodendrocytes, but in a delayed time course (only after 3-4 weeks) compared to rodent counterparts. (2) Similar to results in rodent systems, increasing intracellular levels of the second messenger cAMP promotes a 2-fold increase in differentiation of OPC into O4+ cells. Similarly, activation of peroxisomal proliferator-activated receptors (PPARs), a superfamily of ligand-activated transcription factors, increases OPC differentiation into O4+ or O1+ cells by 1.5-fold. (3) Co-culturing human fetal OPCs with dorsal root ganglion neurons (DRGs) results promotes O1 expression by OPCs but yet has not produced compact myelin, unlike the results obtained with rodent OPCs (Fragoso, et al. 2007). Fully elucidating the mechanisms that control differentiation of oligodendrocytes would enable us to propagate human OPCs to promote myelin repair in MS.
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