Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
Biomaterials. 2015 Jul;55:1-11. doi: 10.1016/j.biomaterials.2015.03.029. Epub 2015 Apr 5.
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/β-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/β-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.
人尿液来源的干细胞(USCs)具有巨大的细胞治疗应用潜力,因为它们可以通过非侵入性和简单的方法获得。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。在本研究中,首先我们研究了 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 CS 颗粒掺入聚乳酸-共-羟基乙酸(PLGA)中以获得 PLGA/CS 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 USCs 形成的细胞外基质的矿化。结果表明,CS 离子提取物显著增强了细胞增殖、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/β-catenin 信号通路抑制剂卡瓦胡椒素降低了 CS 离子提取物对 USCs 成骨分化的刺激作用,表明 CS 离子提取物观察到的 USCs 成骨分化涉及 Wnt/β-catenin 信号通路。此外,组织学分析表明,PLGA/CS 复合支架显著增强了 USCs 在体内的成骨分化。综上所述,这些结果表明将 USCs 和 PLGA/CS 支架相结合在骨组织再生中具有治疗潜力。