基于多功能诊疗体系促进衰老内皮祖细胞修复血管损伤的研究

衰老致动脉内皮损伤是触发动脉粥样硬化性血管疾病发生发展的关键环节，内皮祖细胞（EPCs）移植疗法是修复血管损伤的重要手段，如何提高衰老EPCs靶向归巢、促进其定向分化、评估移植后的疗效是目前干细胞再生疗法亟待解决的科学难题。本课题拟以EPCs表面的CD34为靶点，构建特异性识别EPCs的多功能纳米载体，体外安全、高效靶向输送归巢基因（CXCR4）、增殖分化基因（VEGF），提高衰老EPCs体内移植后的靶向归巢及定向分化能力；进一步构建特异识别功能的多功能影像探针，携带磁共振显影剂和活体荧光染料，整合磁共振成像和光学成像的优势，以期实现动态监测EPCs体内移植后的分布、归巢、增殖、分化和血管损伤修复的整个生物学过程。本研究预期结果将为明确干细胞修复血管损伤机制、合理选择提高修复能力手段、评价移植后的疗效提供新的视野，从而为推动干细胞防治缺血性血管病的临床转化研究提供更充分的科学依据。

Arterial endothelial injury caused by aging plays a key role in the development of atherosclerosis vascular diseases. Endothelial progenitor cells (EPCs) represents one of the most promising cell-based strategies for the repair of endothelial injury. However, how to enhance the targeted homing to the sites of injured endothelium, accelerate directional differentiating to endothelial cells and evaluate the effect of endothelial injury repair of aging EPCs is so far an unsolved scientific problem. A specific identification the surface CD34 multifunctional nano carrier will be applied to improve the targeted homing and directional differentiation of EPCs by transfer CXCR4 and VEGF gene to EPCs safely and effectively in vitro. Consequently, two different multifunctional imaging probes loaded magnetic resonance imaging contrast or living fluorescent dyes will be used to dynamic monitor the whole biological process of homing, proliferation and differentiation, vascular injury repair of EPCs in vivo. Our present study will provide new perspectives for the mechanism illustration, reasonable improved measures choice and the therapy effect evaluation of EPC vascular injury repair. Also, the present study will offer new scientific evidences for the clinical translational research about the prevention and treatment of ischemic vascular diseases.