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诱导多能干细胞在水凝胶生物材料中向神经元的分化。

Differentiation of induced pluripotent stem cells toward neurons in hydrogel biomaterials.

机构信息

Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan 62102, Republic of China.

出版信息

Colloids Surf B Biointerfaces. 2013 Feb 1;102:405-11. doi: 10.1016/j.colsurfb.2012.08.061. Epub 2012 Sep 6.

DOI:10.1016/j.colsurfb.2012.08.061
PMID:23010124
Abstract

Regeneration of nerve tissue is one of the most significant challenges in contemporary surgical therapy for nervous system injury. This study presents the neuronal differentiation of induced pluripotent stem (iPS) cells in hydrogels comprising alginate and poly(γ-glutamic acid) (γ-PGA) with surface neuron growth factor (NGF). Differentiating iPS cells in NGF-grafted alginate/γ-PGA constructs were identified by immunochemical staining of anti-SSEA-1 and anti-β III tubulin. The results revealed that the pore diameter of hydrogels increased with an increasing weight ratio of alginate to γ-PGA. The porosity slightly decreased with an increasing weight ratio of alginate to hydrogel. In addition, an increase in the weight ratio of alginate to hydrogel raised the swelling ratio. Morphological images of differentiating iPS cells in NGF-grafted alginate/γ-PGA constructs exhibited neuronal characteristics. The surface NGF enhanced the intensity of β III tubulin and inhibited the intensity of SSEA-1 expressed by differentiating iPS cells in cultured constructs, indicating the differentiation of iPS cells toward neurons. NGF-grafted alginate/γ-PGA hydrogels can be efficient biomaterials in the production of neurons from iPS cells for animal study and preclinical trial.

摘要

神经组织的再生是当代神经系统损伤外科治疗中最具挑战性的问题之一。本研究介绍了在包含藻酸盐和聚(γ-谷氨酸)(γ-PGA)的水凝胶中诱导多能干细胞(iPS)细胞向神经元分化的情况,这些水凝胶表面生长有神经生长因子(NGF)。通过对抗 SSEA-1 和抗 β III 微管蛋白的免疫化学染色,鉴定了在 NGF 接枝藻酸盐/γ-PGA 构建体中分化的 iPS 细胞。结果表明,水凝胶的孔径随藻酸盐与 γ-PGA 重量比的增加而增加。随着藻酸盐与水凝胶重量比的增加,孔隙率略有下降。此外,藻酸盐与水凝胶重量比的增加提高了溶胀比。NGF 接枝藻酸盐/γ-PGA 构建体中分化 iPS 细胞的形态图像表现出神经元特征。表面 NGF 增强了培养构建体中分化的 iPS 细胞表达的 β III 微管蛋白的强度,并抑制了 SSEA-1 的表达强度,表明 iPS 细胞向神经元分化。NGF 接枝藻酸盐/γ-PGA 水凝胶可以作为 iPS 细胞生成神经元的有效生物材料,用于动物研究和临床前试验。

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