Human urine-derived stem cells can be induced into osteogenic lineage by silicate bioceramics via activation of the Wnt/β-catenin signaling pathway
Human urine-derived stem cells can be induced into osteogenic lineage by silicate bioceramics via activation of the Wnt/β-catenin signaling pathway
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DOI：
10.1016/j.biomaterials.2015.03.029
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发表时间：
2015-07-01
期刊：
影响因子：
14
通讯作者：
Chang, Jiang
中科院分区：
文献类型：
--
作者：
Guan, Junjie;Zhang, Jieyuan;Chang, Jiang
人尿源性干细胞（USCs）因其无创、简便的获取方法而在细胞治疗中具有巨大的应用潜力。硅酸盐生物陶瓷，包括硅酸钙（CS），可以刺激干细胞的成骨分化。然而，硅酸盐生物陶瓷对USCs成骨分化的影响尚未见报道。本研究首先探讨了CS离子提取物对USCs增殖和成骨分化的影响及其相关机制。将壳聚糖颗粒与聚乳酸-羟基乙酸共聚物（PLGA）复合，制备PLGA/壳聚糖复合支架。然后将USCs接种到这些支架上，随后将其移植到裸鼠体内，以分析USCs的成骨分化和由USCs形成的细胞外基质的矿化。结果表明，CS离子提取物显着增强细胞增殖、碱性磷酸酶（ALP）活性、钙沉积以及某些成骨细胞相关基因和蛋白的表达。此外，Wnt/beta-catenin信号通路抑制剂小豆蔻素可降低CS离子提取物对USCs成骨分化的刺激作用，提示CS离子提取物诱导USCs成骨分化可能与Wnt/beta-catenin信号通路有关。组织学分析显示PLGA/CS复合支架能显著促进USCs在体内的成骨分化。综上所述，这些结果表明了USCs和PLGA/CS支架组合在骨组织再生中的治疗潜力。(C)2015爱思唯尔有限公司版权所有。
Human urine-derived stem cells (USCs) have great application potential for cytotherapy as they can be obtained by non-invasive and simple methods. Silicate bioceramics, including calcium silicate (CS), can stimulate osteogenic differentiation of stem cells. However, the effects of silicate bioceramics on osteogenic differentiation of USCs have not been reported. In this study, at first, we investigated the effects of CS ion extracts on proliferation and osteogenic differentiation of USCs, as well as the related mechanism. CS particles were incorporated into poly (lactic-co-glycolic acid) (PLGA) to obtain PLGA/CS composite scaffolds. USCs were then seeded onto these scaffolds, which were subsequently transplanted into nude mice to analyze the osteogenic differentiation of USCs and mineralization of extracellular matrix formed by USCs in vivo. The results showed that CS ion extracts significantly enhanced cell proliferation, alkaline phosphatase (ALP) activity, calcium deposition, and expression of certain osteoblast-related genes and proteins. In addition, cardamonin, a Wnt/beta-catenin signaling inhibitor, reduced the stimulatory effects of CS ion extracts on osteogenic differentiation of USCs, indicating that the observed osteogenic differentiation of USCs induced by CS ion extracts involves Wnt/beta-catenin signaling pathway. Furthermore, histological analysis showed that PLGA/CS composite scaffolds significantly enhanced the osteogenic differentiation of USCs in vivo. Taken together, these results suggest the therapeutic potential of combining USCs and PLGA/CS scaffolds in bone tissue regeneration. (C) 2015 Elsevier Ltd. All rights reserved.