Rao Rajesh C, Boyd Justin, Padmanabhan Raji, Chenoweth Josh G, McKay Ronald D
Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Stem Cells. 2009 Jan;27(1):116-25. doi: 10.1634/stemcells.2007-0205.
Oligodendrocytes derived in the laboratory from stem cells have been proposed as a treatment for acute and chronic injury to the central nervous system. Platelet-derived growth factor (PDGF) receptor alpha (PDGFRalpha) signaling is known to regulate oligodendrocyte precursor cell numbers both during development and adulthood. Here, we analyze the effects of PDGFRalpha signaling on central nervous system (CNS) stem cell-enriched cultures. We find that AC133 selection for CNS progenitors acutely isolated from the fetal cortex enriches for PDGF-AA-responsive cells. PDGF-AA treatment of fibroblast growth factor 2-expanded CNS stem cell-enriched cultures increases nestin(+) cell number, viability, proliferation, and glycolytic rate. We show that a brief exposure to PDGF-AA rapidly and efficiently permits the derivation of O4(+) oligodendrocyte-lineage cells from CNS stem cell-enriched cultures. The derivation of oligodendrocyte-lineage cells demonstrated here may support the effective use of stem cells in understanding fate choice mechanisms and the development of new therapies targeting this cell type.
实验室中由干细胞衍生而来的少突胶质细胞已被提议用于治疗中枢神经系统的急慢性损伤。已知血小板衍生生长因子（PDGF）受体α（PDGFRα）信号传导在发育和成年期均调节少突胶质细胞前体细胞数量。在此，我们分析了PDGFRα信号传导对富含中枢神经系统（CNS）干细胞的培养物的影响。我们发现，对从胎儿皮质急性分离的CNS祖细胞进行AC133分选可富集对PDGF-AA有反应的细胞。用PDGF-AA处理经成纤维细胞生长因子2扩增的富含CNS干细胞的培养物可增加巢蛋白阳性细胞数量、活力、增殖和糖酵解速率。我们表明，短暂暴露于PDGF-AA可快速有效地从富含CNS干细胞的培养物中获得O4阳性少突胶质细胞系细胞。此处展示的少突胶质细胞系细胞的获得可能有助于在理解命运选择机制以及开发针对这种细胞类型的新疗法方面有效利用干细胞。
