Self-assembling peptide nanofiber scaffolds enhance dopaminergic differentiation of mouse pluripotent stem cells in 3-dimensional culture.
Self-assembling peptide nanofiber scaffolds enhance dopaminergic differentiation of mouse pluripotent stem cells in 3-dimensional culture.
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DOI：
10.1371/journal.pone.0084504
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Su H
中科院分区：
文献类型：
--
作者：
Ni N;Hu Y;Ren H;Luo C;Li P;Wan JB;Su H
胚胎干细胞多巴胺能分化因其在帕金森病的神经修复治疗中具有潜在的应用前景而受到越来越多的关注。传统的二维细胞培养皿中含有各种动物源性基质，如胶原凝胶、层粘连蛋白和基质，广泛用于诱导多巴胺能分化，这可能会限制ESCs产生多巴胺能神经元的效率，并阻碍其在人类治疗中的应用。在这里，我们报道了一种由天然氨基酸制成的自组装肽具有为多巴胺能分化产生真正的3D环境的特性。与层粘胶蛋白包被的2D培养或基质包被的3D培养相比，包被rada16 -1肽衍生纳米纤维支架的小鼠ESCs （R1）和小鼠iPSCs （TTF-1）的多巴胺能分化明显增加。这些分化的神经元表达特定的多巴胺能标记物，并产生适当的动作电位放电模式。与自组装肽纳米纤维支架（SAPNS）中R1或TTF-1分化的多巴胺能神经元数量增加一致，SAPNS培养中多巴胺能分化成熟相关基因的表达水平和多巴胺释放水平均显著升高。研究结果表明，SAPNS为多巴胺能分化提供了一个很有前途的3D培养系统。
Dopaminergic differentiation of embryonic stem cells (ESCs) gains more and more attention worldwide owing to its potential use for neurorestorative therapy for the treatment of Parkinson’s disease. The conventional 2D cell culture on petri dishes with various animal derived substrata such as collagen gels, laminin, and Matrigel is widely used to induce dopaminergic differentiation and it may limit the efficiency in the generation of dopaminergic neurons from ESCs and prevent their application for human therapies. Here, we reported that a self-assembling peptide made from natural amino acids has a property to generate a true 3D environment for dopaminergic differentiation. Mouse ESCs (R1) and mouse iPSCs (TTF-1) embedded in RADA16-I peptide-derived nanofiber scaffolds led to a marked increase in dopaminergic differentiation compared to the laminin-coated 2D culture or Matrigel-encapsulated 3D culture. These differentiated neurons expressed specific dopaminergic markers and produced appropriate patterns of action potential firing. Consistent with the increase in the number of dopaminergic neurons differentiated from R1 or TTF-1 in the self-assembling peptide nanofiber scaffold (SAPNS), both the expression levels of genes that involve in dopaminergic differentiation and maturation and the dopamine release in SAPNS culture were significantly elevated. The results of the study suggest that SAPNS provides a promising 3D culture system for dopaminergic differentiation.
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DOI：
10.1073/pnas.0902396106
发表时间：
2009-05-05
影响因子：
11.1
作者：
Friling, Stina;Andersson, Elisabet;Ericson, Johan
通讯作者：
Ericson, Johan
影响因子：
56.9
作者：
Cukierman, E;Pankov, R;Yamada, KM
通讯作者：
Yamada, KM
DOI：
10.1073/pnas.0404700101
发表时间：
2004-08-24
影响因子：
11.1
作者：
Perrier, AL;Tabar, V;Studer, L
通讯作者：
Studer, L
影响因子：
46.9
作者：
Lee, SH;Lumelsky, N;McKay, RD
通讯作者：
McKay, RD
影响因子：
4.9
作者：
Sieminski, A. L.;Semino, C. E.;Kamm, R. D.
通讯作者：
Kamm, R. D.