Unveiling the improved targeting migration of mesenchymal stem cells with CXC chemokine receptor 3-modification using intravital NIR-II photoacoustic imaging.
Unveiling the improved targeting migration of mesenchymal stem cells with CXC chemokine receptor 3-modification using intravital NIR-II photoacoustic imaging.
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DOI：
10.1186/s12951-022-01513-7
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发表时间：
2022-06-28
影响因子：
10.2
通讯作者：
Ren, Jie
中科院分区：
文献类型：
--
作者：
Lin, Yuejun;Zhou, Hui-chao;Chen, Ningbo;Ren, Yaguang;Gao, Rongkang;Li, Qiaojia;Deng, Yiwen;Han, Xuejiao;Zhang, Xiaoran;Xiang, Andy Peng;Guo, Bing;Liu, Chengbo;Ren, Jie
关键词：
转基因间充质干细胞(MSCs)治疗具有临床应用前景。MSCs靶向迁移能力的优化有赖于对MSCs分布和外渗动力学的准确成像，而相应的成像结果可以用来预测治疗结果和指导治疗方案的优化。在不同的成像方式中，二次近红外(NIR-II)光学分辨率光声显微镜(OR-PAM)具有分辨率高、穿透深、灵敏度高、信本比大等优点。它将是精确监测MSCs的理想选择，尽管到目前为止还没有进行过这方面的测试。将具有较强近红外吸收的穿透性多肽修饰共轭聚合物纳米粒(TAT-CPNPs)用于标记趋化因子受体基因修饰的MSCs，随后在活体NIR-II或PAM下评估其靶向迁移能力。在接触性超敏小鼠炎症耳部趋化因子(C-X-C基序)配体10上调的基础上，成功地诱导出相应受体--趋化因子(C-X-C基序)受体3(CXCR3)高表达的MSCs(MSCCxcr3)。TAT-CPNPs标记使NIR-II光声成像能够识别被1.2厘米厚的鸡胸组织覆盖的MSCCxcr3。纵向OR-PAM成像显示，由于CXCR3基因的修饰，MSCCxcr3的炎症靶向迁移随着时间的推移而增强，这一点得到了组织学分析的进一步验证。TAT-CPNPs辅助的NIR-II PA显像有望监测MSCs的分布和渗出动力学，这将极大地促进MSC治疗的优化。网上版载有补充材料，可在10.1186/s12951-022-01513-7查阅。
Therapy with genetically modified mesenchymal stem cells (MSCs) has clinical translation promise. Optimizing the targeting migratory ability of MSCs relies on accurate imaging of the distribution and extravasation kinetics of MSCs, and the corresponding imaging results could be used to predict therapeutic outcomes and guide the optimization of the treatment program. Among the different imaging modalities, second near-infrared (NIR-II) optical-resolution photoacoustic microscopy (OR-PAM) has merits, including a fine resolution, a deep penetration, a high sensitivity, and a large signal-to-background ratio. It would be an ideal candidate for precise monitoring of MSCs, although it has not been tested for this purpose so far. Penetrating peptide-decorated conjugated polymer nanoparticles (TAT-CPNPs) with strong NIR-II absorbance were used to label chemokine-receptor genetically modified MSCs, which were subsequently evaluated under intravital NIR-II OR-PAM regarding their targeting migratory ability. Based on the upregulation of chemokine (C-X-C motif) ligand 10 in the inflamed ears of contact hypersensitivity mice, MSCs with overexpression of corresponding receptor, chemokine (C-X-C motif) receptor 3 (Cxcr3) were successfully generated (MSCCxcr3). TAT-CPNPs labeling enabled NIR-II photoacoustic imaging to discern MSCCxcr3 covered by 1.2 cm of chicken breast tissue. Longitudinal OR-PAM imaging revealed enhanced inflammation-targeting migration of MSCCxcr3 over time attributed to Cxcr3 gene modification, which was further validated by histological analysis. TAT-CPNPs-assisted NIR-II PA imaging is promising for monitoring distribution and extravasation kinetics of MSCs, which would greatly facilitate optimizing MSC-based therapy. The online version contains supplementary material available at 10.1186/s12951-022-01513-7.
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