Tumor-Targeting gene therapy and regeneration of injured lung by mssenchymal stem cells

1.通过表达CX 3CL 1或NK的间充质干细胞（MSC）靶向基因治疗多发性肺转移瘤41）通过表达CX 3CL 1的MSC治疗肺转移瘤通过经尾静脉注射B16或C26细胞制备肺转移瘤模型。用AdRGDCX 3CL 1离体感染MSC（MSC/CX 3CL 1）。将MSC/CX 3CL 1静脉注射到具有肺转移的小鼠中。这种治疗通过诱导先天性和过继性免疫抑制肺转移的发展。小鼠的存活时间也通过这种治疗延长。2）表达NK 4的MSC治疗肺转移瘤NK 4是一种针对HGF的拮抗剂，HGF诱导肿瘤血管生成、生长和转移。用AdRGDNK 4离体感染MSC（MSC/NK 4）。将MSC/NK 4静脉注射至具有肺转移的小鼠。这种治疗通过抑制血管生成来抑制肺转移的发展。这种治疗也延长了小鼠的存活时间。1）博莱霉素对肺损伤的评价将博莱霉素注入肺内，诱导肺损伤。通过测定Ashicroft评分和羟脯氨酸含量，建立肺损伤的评价方法。2）肺损伤的MSCs治疗方法肺内注射博莱霉素诱导肺损伤。骨髓间充质干细胞静脉注射到用博来霉素预处理的小鼠中。用AdRGDHGF感染MSCs，诱导MSCs分泌HGF。AdRGDHGF感染MSCs后可大量分泌HGF

1.Targeted gene therapy for multiple lung metastases by mesenchymal stem cells (MSCs) expressing CX3CL1 or NK41)Treatment of lung metastases by MSCs expressing CX3CL1Lung metastases models were made by injection of B16 or C26 cells via tail vain. MSCs were infected with AdRGDCX3CL1 ex vivo (MSCs/CX3CL1). The MSCs/CX3CL1 were injected intravenously to the mice with lung metastases. This treatment inhibited development of lung metastases by inducing innate and adoptive immunity. The survival of mice also was prolonged by this treatment. This study is in press in Stem Cells.2)Treatment of lung metastases by MSCs expressing NK4NK4 is an antagonist against HGF which induces tumor angiogenesis, growth, and metastases. MSCs were infected with AdRGDNK4 ex vivo (MSCs/NK4). The MSCs/NK4 were injected intravenously to the mice with lung metastases. This treatment inhibited development of lung metastases by inhibiting angiogenesis The survival of mice also was prolonged by this treatment. This study is in press in Cancer Gene Therpay.2.Treatment of injured lung by MSCs expressing HGF1)Evaluation of lung injury by bleomycinBleomycin was injected intratracheally to the lung to induce lung injury. Methods of lung injury evaluation were established by measuring Ashicroft score and hydroxyproline contents.2)Treatment of injured lung by MSCsBleomycin was injected intratracheally to the lung to induce lung injury. MSCs were intravenously injected to the mice pretreated with bleomycin. Treatment of MSCs improved lung injury.HGF secretion from MSCs infected with AdRGDHGFAdRGDHGF was made. MSCs infected with AdRGDHGF secreted large amount of HGF