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首页> 外文期刊>Advanced Functional Materials >In Situ Crosslinkable Gelatin Hydrogels for Vasculogenic Induction and Delivery of Mesenchymal Stem Cells
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In Situ Crosslinkable Gelatin Hydrogels for Vasculogenic Induction and Delivery of Mesenchymal Stem Cells

机译：原位可交联明胶水凝胶的间充质干细胞的血管生成诱导和传递。

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摘要

Clinical trials utilizing mesenchymal stem cells (MSCs) for severe vascular diseases have highlighted the need to effectively engraft cells and promote pro-angi-ogenic activity. A functional material accomplishing these two goals is an ideal solution as spatiotemporal and batch-to-batch variability in classical therapeutic delivery can be minimized, and tissue regeneration would begin rapidly at the implantation site. Gelatin may serve as a promising biomaterial due to its excellent biocompatibility, biodegradability, and non-immuno/antigenicity. However, the dissolution of gelatin at body temperature and quick enzymatic degradation in vivo have limited its use thus far. To overcome these challenges, an inject-able, in situ crosslinkable gelatin was developed by conjugating enzymatically crosslinkable hydroxyphenyl propionic acid (GHPA). When MSCs are cultured in 3D in vitro or injected in vivo in GHPA, spontaneous endothelial differentiation occurs, as evidenced by marked increases in endothlelial cell marker expressions (Flk1, Tie2, ANGPT1, vWF) in addition to forming an extensive perfusable vascular network after 2-week subcutaneous implantation. Additionally, favorable host macrophage response is achieved with GHPA as shown by decreased iNOS and increased MRC1 expression. These results indicate GHPA as a promising soluble factor-free cell delivery template which induces endothelial differentiation of MSCs with robust neovasculature formation and favorable host response.
机译：利用间充质干细胞（MSCs）治疗严重血管疾病的临床试验强调了有效植入细胞并促进促血管生成活性的需求。实现这两个目标的功能材料是一种理想的解决方案，因为可以最大程度地减少经典治疗中时空和批次间的差异，并且组织再生将在植入部位迅速开始。明胶由于其优异的生物相容性，生物降解性和非免疫/抗原性而可以用作有前途的生物材料。然而，迄今为止，明胶在体温下的溶解和体内酶的快速降解限制了其用途。为了克服这些挑战，通过缀合酶促可交联的羟苯基丙酸（GHPA），开发了一种可注射的原位可交联明胶。当MSC在体外3D培养或在GHPA体内注射时，会发生自发性内皮分化，内皮细胞标志物表达（Flk1，Tie2，ANGPT1，vWF）的显着增加证明了这一点，此外在2次后形成了广泛的可灌注血管网络周皮下植入。此外，如减少的iNOS和增加的MRC1表达所示，用GHPA可以实现良好的宿主巨噬细胞应答。这些结果表明GHPA是有前途的无可溶性因子的细胞递送模板，其诱导具有强大的新脉管系统形成和有利的宿主反应的MSC的内皮分化。

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  • 来源
    《Advanced Functional Materials》 |2014年第43期|6771-6781|共11页
  • 作者

    Sue Hyun Lee; Yunki Lee; Young Wook Chun; Spencer W. Crowder; Pampee P. Young; Ki Dong Park; Hak-Joon Sung;

  • 作者单位

    Dept. of Biomedical Engineering Vanderbilt University Nashville, TN 37235, USA,Center for Stem Cell Biology Vanderbilt University Medical Center Nashville, TN 37235, USA;

    Dept. of Molecular Science and Technology Ajou University Suwon 443-749, South Korea;

    Dept. of Biomedical Engineering Vanderbilt University Nashville, TN 37235, USA,Center for Stem Cell Biology Vanderbilt University Medical Center Nashville, TN 37235, USA;

    Dept. of Biomedical Engineering Vanderbilt University Nashville, TN 37235, USA,Center for Stem Cell Biology Vanderbilt University Medical Center Nashville, TN 37235, USA;

    Dept. of Pathology, Microbiology, and Immunology Vanderbilt University Medical Center Nashville, TN 37235, USA;

    Dept. of Molecular Science and Technology Ajou University Suwon 443-749, South Korea;

    Dept. of Biomedical Engineering Vanderbilt University Nashville, TN 37235, USA,Center for Stem Cell Biology Vanderbilt University Medical Center Nashville, TN 37235, USA;

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