多肽修饰的超顺磁微粒的构建及间充质干细胞在体MRI示踪研究

Stem cell research has been the most significant scientific and technological breakthrough in bioscience field during last few years. Unfortunately, with the extensively clinical applications of stem cells, there is still no desirable contrast agent for tracking stem cells however, which makes it urgent to develop a non-invasive technology of tracking transplanted stem cells in vivo. While the previous studies have proven some drawbacks of present contrast agent such as low resolution, low sensitivity, etc. We propose a novel technique of superparamagnetic particles(SPIO), which is modified by a biocompatible self-assembly short peptide sequence, to improve the effectiveness and quality of contrast. Also the SPIO can lay a technical support for identifying the treatment mechanism of transplanted stem cells. The purpose of this study is to examine the hydrophilic modified effect of self-assembly peptide on the hydrophobic surface of superparamagnetic particles'(SPIO),and preliminary result showed that this modification can prolong the T2 relaxation rate and improve the negative enhancement effect of SPIO dramatically. In addition, the tracer study of mesenchymal stem cells will be performed to select a new contrast agent with best contrasting effect and lowest biological toxicity under a certain condition of suitable concentration and labeling time. In this way, locating and quantitating the transplanted stem cell sustainably and visually can be realized.

干细胞研究是近几年生命科学领域的重大科学技术突破，随着干细胞的大量临床应用，迫切需要有一种在活体上无创示踪移植干细胞的技术，但目前缺乏一种理想的示踪干细胞的对比剂。我们前期研究已通过临床对比剂标记间充质干细胞发现其存在以下不足之处,如分辨率低、敏感性差等。基于以往研究和本课题组的工作积累,我们提出使用具有生物相容性的自组装短肽序列修饰超顺磁微粒（SPIO）制备新型造影剂，以提高显影效果，有望为明确干细胞移植治疗机制提供技术支持。本研究拟系统性地研究这种亲水的序列对超顺磁微粒疏水表面的亲水修饰作用，初步实验发现此自组装多肽超顺磁微粒通过延长SPIO的弛豫率使其在T2 像上呈现出很强的负增强效果；另外通过对间充质干细胞的示踪研究，筛选出适当浓度和标记时间的显影效果最佳、生物毒性最低的新型对比剂，从而实现对移植干细胞行可持续性可视化定位定量评价。

干细胞研究是近几年生命科学领域的重大科学技术突破,随着干细胞的大量临床应 用,迫切需要有一种在活体上无创示踪移植干细胞的技术,但目前缺乏一种理想的示踪 干细胞的对比剂。我们前期研究已通过临床对比剂标记间充质干细胞发现其存在以下不 足之处,如分辨率低、敏感性差等。基于以往研究和本课题组的工作积累,我们提出使用具有生物相容性的自组装短肽序列修饰超顺磁微粒(SPIONs)制备新型造影剂,以提高显影效果,有望为明确干细胞移植治疗机制提供技术支持。本实验设计一段两亲性自组装多肽修饰的SPIONs作为新型的MRI造影剂，并用于大鼠源间充质干细胞（MSCs）的标记。研究结果表明该多肽化SPIONs在MSCs标记与追踪上极具应用潜力。该纳米粒在水溶液条件下展示出良好的单分散性与稳定性。弛豫性能方面，在7.0 T 磁场条件下，多肽修饰可提高SPIONs的r2值达到194.2 s-1 /mM。细胞由多肽化SPIONs标记，结果显示新型的纳米颗粒具有更高的内在化效率，更高效的T2加权成像结果，以及对MSCs更低的细胞毒性。这些结果均有效证明了该自组装多肽修饰的SPIONs可作为MSCs的标记与体内示踪的潜在造影剂候选，有望用于以后的MRI辅助诊断与治疗。