生物纳米颗粒修饰对骨髓间充质干细胞向神经诱导分化的调控

Bionanoparticles, such as plant virus and ferritin are especially attractive for development in drug delivery, tissue engineering and nanoblock chemistry because of their unique structure character and properties. Our recent study demonstrated that turnip yellow mosaic virus (TYMV), cucumber mosaic virus (CMV), and ferritin etc. are useful nano-scale building blocks for polyvalent display of various functional motifs; Bionaoparticles, which combined multiple functions of targeting, imaging, induction, self-assembly and nano-meter surface feature, showed superior in vitro performance in comparison with traditional materials. Our published results pave the way for other possible bionanoparticle-based nanosensors, drug delivery carrier or tissue engineering materials using different cell recognition motifs. In this proposal, various kind of bionanoparticle will be employed to anchor different introduction motifs either by site specific mutation or chemical derivatization. Whether the derivatized binonanoparticle can regulate the neural differentiation of bone marrow mesenchymal stem cell will be explored，MALDI-TOF, FPLC, HPLC, affinity chromatography, TEM, SEM, SDS-PAGE, western blot, fluorescence quantification, ELISA, immunohistochemistry, real-time PCR analysis will be used to disclose the corresponding mechanism. Our research aim to build bionanoparticles as a multifunctional material platform for nerve regeneration, expedite the development of bionanotechnology.

植物病毒和铁蛋白等生物纳米颗粒的独特结构特征为开发新型的医用材料提供了诱人的机会。我们最近的研究表明，植物病毒和铁蛋白等生物纳米颗粒是可偶联多种分子的多功能平台，生物纳米颗粒表面键接的官能团可在纳米尺度上通过自组装调节材料表面的生物学性能，较其它传统的材料有明显的优越性。本研究拟采用MALDI-TOF、FPLC、扫描和透射电镜、酶联免疫吸附、荧光定量、免疫组化分析、实时定量PCR等分析技术，结合位点特异性突变、化学衍生化修饰等方法，深入研究在生物纳米颗粒经促神经生长多肽等特定官能团修饰后对骨髓间充质干细胞向神经诱导分化的影响，探讨用生物纳米颗粒诱导骨髓间充质干细胞向神经分化的机理，完善和优化骨髓间充质干细胞向神经元定向分化的材料体系，为后期高效获得功能性神经元奠定基础。本研究将为神经再生提供一个多用途的新材料平台，并推动生物纳米科技的发展。

用适当的细胞外基质调节干细胞向特定谱系特异性分化是干细胞研究的重要方向之一，细胞外基质的硬度、纳米形貌、表面化学基团都会影响干细胞的分化。植物病毒纳米颗粒因独特结构成为可偶联多种分子的多功能平台，其表面键接的多价官能团可调节材料表面的生物学性能。在这项研究中，我们利用烟草花叶病毒（TMV）偶联多价促神经突起生长的IKVAV肽段（称为TMV-IKVAV）以促进骨髓间充质干细胞（MSCs）在其表面粘附、增殖以及在有视黄酸存在时向神经细胞分化。将在TMV-IKVAV基质表面培养的向神经分化的骨髓间充质干细胞移植入SD大鼠脊髓横断模型中的横断部位，可促进脊髓损伤后的重建并再生出轴突高线性成束的结构。我们的研究结果勾勒出一种形式的中枢神经系统再生，对推动制备多用途的促组织修复生物纳米颗粒平台具有重要参考意义。