基于多模态分子MGd的MRI评价携带自杀基因的新型人源间充质干细胞移植治疗胆管癌肝转移的研究

胆管癌的转移致死率极高。传统的放化疗基本无效且造成极大毒副作用。以间充质干细胞为载体的基因治疗技术为胆管癌转移的治疗带来了新希望。但由于传统来源干细胞的数量受到限制，进展缓慢。人胚胎干细胞来源的间质祖细胞（hESC-MPs）可以归巢到肿瘤转移部位，并可通过无限获得的胚胎干细胞分化而得到，解决了细胞来源这一临床应用的瓶颈问题，是治疗基因的优良载体。以hESC-MPs作为单纯疱疹病毒胸苷激酶基因载体结合腺相关病毒(AAV)介导的基因转染体系，可实现对肿瘤转移灶的精准投放和靶向治疗。多模态T1对比剂MGd标记移植用的hESC-MPs后，可以通过MRI监测hESC-MPs向靶部位归巢的路径和体内分布，并进而实现对基因药物在靶部位的作用时间和剂量的动态调整。因此以hESC-MPs为治疗基因载体结合MGd标记hESC-MPs后体内分布和治疗效果的MRI监测将为转移性肿瘤治疗开辟一条新通路。

The lethality of cholangiocarcinoma is high. The chemotherapy and radiotherapy is largely ineffective and cause great side effects. A new approach arise with the mesenchymal stem cells as a carrier of the therapeutic genes for the treatment of cholangiocarcinoma. But it is limited because of the rare number of stem cells for treatment, the progress is slow. Human embryonic stem cell-derived mesenchymal progenitor cells (hESC-MPs) may home to sites of metastasis , meanwhile those can be obtained from unlimited human embryonic stem cells. Thus the bottleneck problem of the source of stem cell is solved. The combination of hESC-MPs as herpes simplex virus thymidine kinase gene carrier with adeno-associated virus vector (AAV) -mediated gene transfer system may realize targeted therapy for tumor metastases. After transplantion of marked hESC-MPs by multi-modal T1 contrast agent MGd was completed, the homing path and distribution of hESC-MPs in vivo can be monitored by MRI. Dynamic adjustment of gene drug dose and time of drug action at the target site may achieved. Therefore, combination of treatment of hESC-MPs as gene carrier with MRI monitoring based MGd may be an new pathway for the therapy of metastatic tumors.