Aizawa Yukie, Leipzig Nic, Zahir Tasneem, Shoichet Molly
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Canada.
Biomaterials. 2008 Dec;29(35):4676-83. doi: 10.1016/j.biomaterials.2008.08.018. Epub 2008 Sep 17.
Neural stem/progenitor cells (NSPCs) hold great promise in regenerative medicine; however, controlling their differentiation to a desired phenotype within a defined matrix is challenging. To guide the differentiation of NSPCs, we first created a cell-adhesive matrix of agarose modified with glycine-arginine-glycine-aspartic acid-serine (GRGDS) and then demonstrated the multipotentiality of NSPCs to differentiate to the three primary cell types of the central nervous system on this matrix: neurons, oligodendrocytes and astrocytes. We then examined whether immobilized platelet derived growth factor AA (PDGF-AA) would promote differentiation similarly to the same soluble factor and found similar percentages of NSPCs differentiated to oligodendrocytes as determined by immunohistochemistry (IHC) and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Interestingly, the gene expression of the differentiated oligodendrocytes was similar for 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) but different for myelin oligodendrocyte glycoprotein (MOG) in the presence of soluble PDGF-AA vs. immobilized PDGF-AA. These results demonstrate for the first time, that it is possible to control the differentiation of NSPCs, and specifically to oligodendrocytes, in cell-adhesive matrices with immobilized PDGF-AA.
神经干/祖细胞(NSPCs)在再生医学中极具前景;然而,在特定基质内将其分化控制为所需表型具有挑战性。为了引导NSPCs的分化,我们首先创建了一种用甘氨酸-精氨酸-甘氨酸-天冬氨酸-丝氨酸(GRGDS)修饰的琼脂糖细胞粘附基质,然后证明了NSPCs在该基质上分化为中枢神经系统三种主要细胞类型的多能性:神经元、少突胶质细胞和星形胶质细胞。然后,我们研究了固定化血小板衍生生长因子AA(PDGF-AA)是否会与相同的可溶性因子一样促进分化,并通过免疫组织化学(IHC)和定量逆转录-聚合酶链反应(qRT-PCR)发现,分化为少突胶质细胞的NSPCs百分比相似。有趣的是,在存在可溶性PDGF-AA与固定化PDGF-AA的情况下,分化的少突胶质细胞的2',3'-环核苷酸3'-磷酸二酯酶(CNPase)基因表达相似,但髓鞘少突胶质细胞糖蛋白(MOG)的基因表达不同。这些结果首次证明,在含有固定化PDGF-AA的细胞粘附基质中,有可能控制NSPCs的分化,特别是向少突胶质细胞的分化。