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

肿瘤靶向基因治疗和间充质干细胞损伤肺的再生

基本信息

批准号：
16390232
负责人：
SAIJO Yasuo
金额：
$ 9.28万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390232/
关键词：
mesenchymal stem cells CX3CL1 lung metastases HGF lung injury gene therapy NK4 肺傷害固形腫瘍アデノウイルスベクター骨髄由来間葉系幹細胞

项目摘要

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

1.表达CX3CL1或NK41的间充质干细胞（mesenchymal stem cells, MSCs）靶向基因治疗多发性肺转移瘤用表达CX3CL1的间充质干细胞治疗肺转移瘤用尾静脉注射B16或C26细胞制备肺转移瘤模型。AdRGDCX3CL1在体外感染MSCs （MSCs/CX3CL1）。将MSCs/CX3CL1静脉注射到肺转移小鼠。这种治疗通过诱导先天免疫和过继免疫抑制肺转移的发展。小鼠的存活时间也得到了延长。2)表达nk4的MSCs治疗肺转移瘤nk4是HGF的拮抗剂，可诱导肿瘤血管生成、生长和转移。AdRGDNK4在体外感染MSCs （MSCs/NK4）。将MSCs/NK4静脉注射到肺转移小鼠体内。该治疗通过抑制血管生成来抑制肺转移的发展，并延长了小鼠的存活时间。这项研究发表在《癌症基因治疗》杂志上。表达HGF1的间充质干细胞治疗肺损伤的研究博来霉素肺损伤的评价通过气管内注射博来霉素诱导肺损伤。通过测定Ashicroft评分和羟脯氨酸含量，建立肺损伤评价方法。2)损伤肺的治疗：气管内注射博来霉素，诱导肺损伤。经博来霉素预处理的小鼠静脉注射间充质干细胞。MSCs治疗可改善肺损伤。转染AdRGDHGFAdRGDHGF的MSCs分泌HGF。感染AdRGDHGF的MSCs分泌大量HGF

项目成果

期刊论文数量（33）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Vaccination of dendritic cells loaded with interleukin-12-secreting cancer cells augments in vivo antitumor immunity :

接种负载有白细胞介素 12 分泌癌细胞的树突状细胞可增强体内抗肿瘤免疫力：

DOI：
发表时间：
2005
期刊：
Clinical Cancer Research 11
影响因子：
0
作者：
Suzuki T;Saijo Y et al.
通讯作者：
Saijo Y et al.

Infiltration of COX-2-expressing macrophages is a prerequisite for IL-1 beta-induced neovascularization.

表达 COX-2 的巨噬细胞的浸润是 IL-1 β 诱导的新血管形成的先决条件。

DOI：
发表时间：
2005
期刊：
J Clin Invest 115
影响因子：
0
作者：
Inoue A;Usui K;Kanbe M;Gomi K;Koinumaru S;Saijo Y;Nukiwa T.;Nakao S;Kikuchi T;Xin H;Suzuki T;Nakao S
通讯作者：
Nakao S

Involvement of Fractalkine/CX3CL1 expression by dendritic immunity against Legionella peumophilia cells in the enhancement of host

Fractalkine/CX3CL1 表达通过针对嗜肺军团菌细胞的树突状免疫增强宿主

DOI：
发表时间：
2005
期刊：
Infect Immun 73
影响因子：
0
作者：
Inoue A;Usui K;Kanbe M;Gomi K;Koinumaru S;Saijo Y;Nukiwa T.;Nakao S;Kikuchi T;Xin H;Suzuki T;Nakao S;Kikuchi T
通讯作者：
Kikuchi T

Antitumor Immune Response by CX3CL1 Fractalkine Gene Transfer Depends on both NK and Cells

CX3CL1 Fractalkine 基因转移的抗肿瘤免疫反应取决于 NK 和细胞