TNF-α预激活的人脐带间充质干细胞靶向治疗乳腺癌的分子影像学研究

The tumor tropism of mesenchymal stem cells (MSCs) allows them to engraft into the tumor microenvironment and serves as vehicles for delivering therapeutic agents to isolated tumors and metastases. Molecular imaging enables the longitudinal, noninvasive assessment of cell fate and function in vivo following cell transplantation, which makes it an invaluable tool in tracking cell delivery and tumor response in MSC therapies. We found previously that the incubation of human umbilical cord-derived MSCs with tumor necrosis factor-α (TNF-α) activated the expression of tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL), which has cancer apoptotic activity, and significantly inhibited the progression of breast cancer cells (MDA-MB-231). In this proposal, bioluminescence imaging of double-fusion reporter genes will be developed for tracking TNF-α pre-activated MSCs and the tumor cells simultaneously. Moreover, near-infrared imaging will be used to monitor the tumor angiogenesis and apoptosis in mouse breast cancer models. We are hopeful that this project will illuminate: first, molecular imaging technologies can well monitor and evaluate MSC delivery and antitumor activity of MSC therapy; second, TNF-α pre-activated hUC-MSCs may represent a useful strategy to develop MSCs-based approaches for the treatment of breast cancer. Furthermore, the important theory basis will be provided for clinical studies.

间充质干细胞（MSCs）能够归巢到实体肿瘤原发及转移病灶，作用于肿瘤微环境，是良好的肿瘤靶向治疗载体。分子影像能够无创、实时的监测移植细胞的命运和功能，为评价干细胞治疗肿瘤提供了有力工具。前期研究发现人脐带间充干细胞（hUC-MSCs）在孵育肿瘤坏死因子（TNF-α）后，TNF-α相关凋亡诱导配体（TRAIL）被激活，抑制肿瘤的效果显著增强。本项目将通过双融合报告基因方法标记TNF-α预激活的hUC-MSCs（pre-activated MSCs），以生物发光成像和近红外成像为主要工具，结合体外实验，长时间动态的监测pre-activated MSCs靶向治疗乳腺癌的效果和安全性，探索pre-activated MSCs抑制乳腺癌生长的机理。本项目能够：1）阐明分子影像可以较好的监测并评价干细胞靶向治疗肿瘤；2）为以MSCs为载体治疗乳腺癌提供新的可能策略，为临床试验提供理论基础和依据。

间充质干细胞（MSCs）能够归巢到实体肿瘤原发及转移病灶，作用于肿瘤微环境，是良好的肿瘤靶向治疗载体。分子影像能够无创、实时的监测移植细胞的命运和功能，为评价干细胞治疗肿瘤提供了有力工具。 本项目通过双融合报告基因方法标记TNF-α预激活的hUC-MSCs（pre-activated MSCs），以生物发光成像和近红外成像为主要工具，结合体外实验，动态的监测了pre-activated MSCs靶向治疗乳腺癌的效果和安全性，探索了pre-activated MSCs抑制乳腺癌生长的机理。本项目阐述了分子影像可以较好的监测并评价干细胞靶向治疗肿瘤；为以MSCs为载体治疗乳腺癌提供新的可能策略，为临床试验提供理论基础和依据。