MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350108, P.R. China.
Nanoscale. 2021 Jan 28;13(3):1813-1822. doi: 10.1039/d0nr07272a.
Adipose tissue-derived mesenchymal stem cell (ADSC)-based therapy is attractive for liver diseases, but the long-term therapeutic outcome is still far from satisfaction due to the low hepatic engraftment efficiency of ADSC transplantation. Herein, we propose a strategy based on liver sinusoidal endothelial cell (LSEC)-targeting peptide modification and near infrared (NIR) fluorescent probe labeling for enhancing LSEC-barrier-migration ability and in vivo tracking of ADSCs in a liver injury mouse model. RLTRKRGLK (RK), a LSEC-targeted peptide, and indocyanine green (ICG), a FDA approved infrared fluorescent dye, were simultaneously modified on the ADSC surface via a bioorthogonal click reaction. The equipped ADSCs not only exhibited significant binding ability towards LSEC both in vitro and in vivo, but could also be monitored by NIR imaging in vivo. In particular, the RK-modified ADSCs showed remarkable higher hepatic accumulation as compared to unmodified ADSCs, resulting in better therapeutic outcomes. Therefore, this study provides a simple and convenient method for enhancing the homing of transplanted ADSCs to injured liver accompanying with in vivo cell tracking ability, which may shed light on accelerating the clinical translation of the ADSC-based therapy for liver diseases.
脂肪组织来源的间充质干细胞（ADSC）为基础的治疗方法对于肝脏疾病具有吸引力，但由于 ADSC 移植的肝内植入效率低，其长期治疗效果仍远未令人满意。在此，我们提出了一种基于肝窦内皮细胞（LSEC）靶向肽修饰和近红外（NIR）荧光探针标记的策略，以增强 LSEC-屏障迁移能力，并在肝损伤小鼠模型中对 ADSC 进行体内跟踪。RLTRKRGLK（RK）是一种 LSEC 靶向肽，吲哚菁绿（ICG）是一种 FDA 批准的近红外荧光染料，通过生物正交点击反应同时修饰在 ADSC 表面。修饰后的 ADSC 不仅在体外和体内表现出对 LSEC 的显著结合能力，而且可以通过体内 NIR 成像进行监测。特别是，与未修饰的 ADSC 相比，RK 修饰的 ADSC 表现出更高的肝内蓄积，从而产生更好的治疗效果。因此，本研究提供了一种简单方便的方法，可增强移植的 ADSC 向受损肝脏的归巢能力，并具有体内细胞跟踪能力，这可能为加速基于 ADSC 的肝脏疾病治疗的临床转化提供新的思路。
