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首页> 外文期刊>Biomaterials Science >Tubulogenesis of co-cultured human iPS-derived endothelial cells and human mesenchymal stem cells in fibrin and gelatin methacrylate gels
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Tubulogenesis of co-cultured human iPS-derived endothelial cells and human mesenchymal stem cells in fibrin and gelatin methacrylate gels

机译：共培养人IPS衍生的内皮细胞和纤维蛋白和明胶甲基丙烯酸甲酯凝胶中的人间充质干细胞的微管发生

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摘要

Here, we investigate the tubulogenic potential of commercially-sourced iPS-ECs with and without supporting commercially-sourced hMSCs within 3D natural fibrin or semi-synthetic gelatin methacrylate (GelMA) hydrogels. We developed a selectable dual color third generation lentiviral reporter (hEF1a-H2BmOrange2-IRES-EGFP PGK-Puro) to differentially label the nucleus and cytoplasm of iPS-ECs which allowed real-time tracking of key steps of vascular morphogenesis such as vacuole formation and coalescence to form shared multicellular lumens. We implement 3D quantification of the network character and validate that transduced and untransduced iPS-ECs can form tubules in fibrin with or without supporting hMSCs. In addition to natural fibrin gels, we also investigated tubulogenesis in GelMA, a semisynthetic material that has received increased interest due to its ability to be photopatterned and 3D printed, and which may thus boost development of complex 3D models for regenerative medicine studies. We find that iPS-ECs alone have a muted tubulogenic response within GelMA, but that their tubulogenic response is enhanced when they are co-cultured with a small fraction of hMSCs (2% of total cells). Our work bolsters previous findings by validating established tubulogenic mechanisms with commercially available iPS-ECs, and we expect our findings will benefit biologic studies of vasculogenesis and will have applications in tissue engineering to pre-vascularize tissue constructs which are fabricated with advanced photopatterning and three-dimensional printing.
机译：在这里，我们研究了商业源性IPS-ECS的微孔潜力，并且不支持在3D天然纤维蛋白或半合成明胶甲基丙烯酸酯（GELMA）水凝胶中的商业源于商业化的HMSC。我们开发了一种可选择的双色第三代慢病毒报告器（HEF1A-H2BMORANGE2-IRES-EGFP PGK-PURO），以差异地标记IPS-EC的细胞核和细胞质，允许实时跟踪血管形态发生的关键步骤，例如液泡形成和液体形成结合形成共用多细胞流明。我们实施网络字符的3D量化，并验证转导和未经转化的IPS-EC可以在具有或不支持HMSC的纤维蛋白中形成小管。除了天然纤维蛋白凝胶外，我们还在GELMA中调查了小管发生，这是一种半合成材料，这是由于其被照射的能力和3D印刷的能力而受到增加的利益，因此可以促进复合3D模型的开发进行再生医学研究。我们发现单独的IPS-EC在凝胶中的柔软小微分响应，但是当它们共同培养时，它们的微管响应在用少量HMSC（占总细胞的2％）中时增强。我们的工作通过验证具有商业上可用的IPS-ECS的成熟的小管生机制，我们预计我们的发现将使我们的研究结果受益于血管生成的生物学研究，并将在组织工程中应用于血管形成的组织构建体，这些组织构建体由先进的PhotoPatterning制造和三个 - 尺寸印刷。

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  • 来源
    《Biomaterials Science》 |2017年第8期|共9页
  • 作者

    Calderon G. A.; Thai P.; Hsu C. W.; Grigoryan B.; Gibson S. M.; Dickinson M. E.; Miller J. S.;

  • 作者单位

    Rice Univ Dept Bioengn 6100 Main St Houston TX 77005 USA;

    Rice Univ Dept Bioengn 6100 Main St Houston TX 77005 USA;

    Baylor Coll Med Dept Mol Physiol &

    Biophys One Baylor Plaza Houston TX 77030 USA;

    Rice Univ Dept Bioengn 6100 Main St Houston TX 77005 USA;

    Rice Univ Dept Bioengn 6100 Main St Houston TX 77005 USA;

    Baylor Coll Med Dept Mol Physiol &

    Biophys One Baylor Plaza Houston TX 77030 USA;

    Rice Univ Dept Bioengn 6100 Main St Houston TX 77005 USA;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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