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肽修饰的纳米纤维龛增强人多能干细胞体外定向成骨分化。

Peptide-Decorated Nanofibrous Niche Augments In Vitro Directed Osteogenic Conversion of Human Pluripotent Stem Cells.

机构信息

School of Chemical Engineering, Sichuan University , Chengdu 610065, China.

Department of Materials Engineering, Sichuan College of Architectural Technology , Deyang 618000, China.

出版信息

Biomacromolecules. 2017 Feb 13;18(2):587-598. doi: 10.1021/acs.biomac.6b01748. Epub 2017 Jan 24.

DOI:10.1021/acs.biomac.6b01748
PMID:28068081
Abstract

Realization of clinical potential of human pluripotent stem cells (hPSCs) in bone regenerative medicine requires development of simple and safe biomaterials for expansion of hPSCs followed by directing their lineage commitment to osteoblasts. In the present study, a chemically defined peptide-decorated polycaprolactone (PCL) nanofibrous microenvironment was prepared through electrospinning technology and subsequent conjugation with vitronectin peptide to promote the culture and osteogenic potential of hPSCs in vitro. The results indicated that hPSCs successfully proliferated and maintained their pluripotency on the biointerface of peptide-conjugated nanofibers without Matrigel under defined conditions. Moreover, the prepared niche exhibited an appealing ability in promoting directed differentiation of hPSCs to osteoblastic phenotype without embryoid body formation step, determined from the cell morphological alteration, alkaline phosphate activity, and osteogenesis-related gene expression, as well as protein production. Such well-defined, xeno-free, and safe nanofiber scaffolds that allow the survival and facilitate osteo-differentiation of hPSCs provide a novel platform for hPSCs differentiation via cell-nanofiber interplay, and possess great value in accelerating the translational perspectives of hPSCs in bone tissue engineering.

摘要

在骨再生医学中实现人类多能干细胞(hPSCs)的临床潜力,需要开发简单、安全的生物材料来扩增 hPSCs,然后指导其向成骨细胞分化。本研究通过静电纺丝技术制备了一种化学定义的肽修饰的聚己内酯(PCL)纳米纤维微环境,并通过与纤连蛋白肽缀合来促进 hPSCs 在体外的培养和成骨潜能。结果表明,hPSCs 在不使用 Matrigel 的定义条件下,在肽修饰纳米纤维的生物界面上成功增殖并保持其多能性。此外,该制备的小生境在促进 hPSCs 向成骨表型的定向分化方面表现出吸引力,而无需形成胚状体步骤,这可以从细胞形态改变、碱性磷酸酶活性、成骨相关基因表达以及蛋白质产生来确定。这种具有明确定义、无动物源和安全的纳米纤维支架,允许 hPSCs 的存活并促进其成骨分化,为通过细胞-纳米纤维相互作用来分化 hPSCs 提供了一个新的平台,在加速 hPSCs 在骨组织工程中的转化方面具有重要价值。

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