Biomaterials:基因处理增强干细胞的成骨效果

2018-03-16 MedSci MedSci原创

当培养基补充有蛋白质(例如生长因子(GF))时,可以引导高密度间充质干细胞(MSC)聚集体通过体外软骨内成骨来形成骨样组织,首先引导软骨模板的形成,随后用肥大因子培养。 近期研究报道通过从嵌入在人MSC集合体内的微粒控制软骨形成转化生长因子-β1(TGF-β1)和软骨形成及成骨骨形态发生蛋白-2(BMP-2)的受控时空递送来重现这些结果,以避免重复补充昂贵的外源必需的体外培养。然而,由于GF

当培养基补充有蛋白质(例如生长因子(GF))时,可以引导高密度间充质干细胞(MSC)聚集体通过体外软骨内成骨来形成骨样组织,首先引导软骨模板的形成,随后用肥大因子培养。

近期研究报道通过从嵌入在人MSC集合体内的微粒控制软骨形成转化生长因子-β1(TGF-β1)和软骨形成及成骨骨形态发生蛋白-2(BMP-2)的受控时空递送来重现这些结果,以避免重复补充昂贵的外源必需的体外培养。然而,由于GFs稳定性有限,局部基因递送是蛋白质使用的一种有希望的替代方案。

本研究中,将能够局部递送编码TGF-β1(pTGF-β1)和BMP-2(pBMP-2)的Lipofectamine-质粒DNA(pDNA)纳米复合物的羟基磷灰石微粒(MCM)单独或组合地整合至来自三个健康猪供体MSC中以诱导这些转基因的持续表达。由于在文献中记载的MSC供体对供体的分化能力的不同,本研究中探究了三个供体群体。

在供体1中聚集的pBMP-2聚集促进了第2周的软骨形成,随后在第4周增强了成骨表型。供体2和3聚集在第2周时不促进葡糖胺聚糖(GAG)产生,但是在第4周时促进其产生。具有pTGF-β1/pBMP-2的供体2和具有MCM和pBMP-2的供体3可增强骨生成。

这些结果表明,在细胞群中通过控制的非病毒基因递送来促进干细胞聚集体中骨生成的能力。这些发现还表明,在临床应用之前需要筛选供体MSC再生潜能以响应基因转移。总之,这项工作展示了一种有前途的基因治疗方法来控制仿生3D凝聚中干细胞的转化以治疗骨缺损。

原始出处:


McMillan A, Nguyen MK, et al., Dual non-viral gene delivery from microparticles within 3D high-density stem cell constructs for enhanced bone tissue engineering. Biomaterials. 2018 Apr;161:240-255. doi: 10.1016/j.biomaterials.2018.01.006. Epub 2018 Jan 3.

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    2018-08-21 sunylz
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    2018-03-18 zhaojie88
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    2018-03-17 changjiu

    学习一下谢谢

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