2006 Fiscal Year Final Research Report Summary
Tumor-Targeting gene therapy and regeneration of injured lung by mssenchymal stem cells
| Project/Area Number |
16390232
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Tohoku University |
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Principal Investigator |
SAIJO Yasuo Tohoku University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (10270828)
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| Co-Investigator(Kenkyū-buntansha) |
NUKIWA Toshihiro Tohoku University, Institute of Development Aging, and Cancer, Professor, 加齢医学研究所, 教授 (40129036)
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| Project Period (FY) |
2004 – 2006
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| Keywords | mesenchymal stem cells / CX3CL1 / lung metastases / HGF / lung injury / gene therapy / NK4 |
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| Research Abstract |
1.Targeted gene therapy for multiple lung metastases by mesenchymal stem cells (MSCs) expressing CX3CL1 or NK4
1)Treatment of lung metastases by MSCs expressing CX3CL1
Lung 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 NK4
NK4 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 HGF
1)Evaluation of lung injury by bleomycin
Bleomycin 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 MSCs
Bleomycin 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 AdRGDHGF
AdRGDHGF was made. MSCs infected with AdRGDHGF secreted large amount of HGF
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