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人胚胎干细胞在层粘连蛋白衍生合成肽丙烯酸酯表面向少突胶质前体细胞的分化。

Differentiation of oligodendrocyte progenitor cells from human embryonic stem cells on vitronectin-derived synthetic peptide acrylate surface.

机构信息

Geron Corporation , Menlo Park, California, USA.

出版信息

Stem Cells Dev. 2013 May 15;22(10):1497-505. doi: 10.1089/scd.2012.0508. Epub 2013 Feb 13.

Abstract

Human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) are being studied for cell replacement therapies, including the treatment of acute spinal cord injury. Current methods of differentiating OPCs from hESCs require complex, animal-derived biological extracellular matrices (ECMs). Defined, low-cost, robust, and scalable culture methods will need to be developed for the widespread deployment and commercialization of hESC-derived cell therapies. Here we describe a defined culture system that uses a vitronectin-derived synthetic peptide acrylate surface (VN-PAS; commercially available as Corning(®) Synthemax(®) surface) in combination with a defined culture medium for hESC growth and differentiation to OPCs. We show that synthetic VN-PAS supports OPC attachment and differentiation, and that hESCs grown on VN-PAS are able to differentiate into OPCs on VN-PAS. Compared to OPCs derived from hESCs grown on ECM of animal origin, higher levels of NG2, a chondroitin sulfate proteoglycan expressed by OPCs, were observed in OPCs differentiated from H1 hESCs grown on VN-PAS, while the expression levels of Nestin and PDGFRα were comparable. In summary, this study demonstrates that synthetic VN-PAS can replace complex, animal-origin ECM to support OPC differentiation from hESCs.

摘要

人胚胎干细胞(hESC)衍生的少突胶质前体细胞(OPC)正在被研究用于细胞替代疗法,包括急性脊髓损伤的治疗。目前从 hESC 分化 OPC 的方法需要复杂的、源自动物的生物细胞外基质(ECM)。需要开发定义明确、成本低、稳健且可扩展的培养方法,以便广泛部署和商业化 hESC 衍生的细胞疗法。在这里,我们描述了一种使用纤连蛋白衍生的合成肽丙烯酸酯表面(VN-PAS;可商购获得,称为康宁® Synthemax®表面)与定义明确的培养基结合的定义明确的培养系统,用于 hESC 生长和分化为 OPC。我们表明,合成的 VN-PAS 支持 OPC 的附着和分化,并且在 VN-PAS 上生长的 hESC 能够分化为 VN-PAS 上的 OPC。与源自动物来源 ECM 的 hESC 衍生的 OPC 相比,在从 VN-PAS 上生长的 H1 hESC 分化而来的 OPC 中观察到更高水平的 NG2,一种 OPC 表达的软骨素硫酸盐蛋白聚糖,而 Nestin 和 PDGFRα 的表达水平相当。总之,这项研究表明,合成的 VN-PAS 可以替代复杂的、源自动物的 ECM,以支持 hESC 分化为 OPC。

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