Cell and gene therapy using mesenchymal stem cells (MSCs)
Cell and gene therapy using mesenchymal stem cells (MSCs)
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DOI：
10.1016/j.jaut.2007.12.008
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发表时间：
2008-05-01
影响因子：
12.8
通讯作者：
Kume, Akihiro
中科院分区：
文献类型：
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作者：
Ozawa, Keiya;Sato, Kazuya;Kume, Akihiro
骨髓间充质干细胞（MSC）被认为是一个有前途的平台，为各种疾病的细胞和基因治疗。首先，在造血干细胞移植领域，MSC有两个应用：1）基于造血支持能力的干细胞移植的改善和造血重建的加速;和2）基于免疫调节能力的严重移植物抗宿主病（GVHD）的治疗。关于免疫抑制能力，我们发现一氧化氮（NO）参与MSC介导的T细胞增殖抑制。第二，向荷瘤裸鼠注射表达端粒酶的MSC。体内成像分析显示MSC在肿瘤部位的显著积累。研究结果表明，MSC可用于靶向转移性肿瘤并局部递送抗癌分子。作为第三种应用，MSC可以用作蛋白质补充基因治疗的细胞载体。当需要长期的转基因表达时，治疗性基因应该以最小的插入诱变风险被引入。为此，通过使用腺相关病毒（AAV）的整合机制位点特异性整合到染色体19（19q13.4）上的AAVS 1基因座中将是特别有价值的。骨髓间充质干细胞在未来的医学前沿领域有着广泛的应用前景。(C)2008爱思唯尔有限公司保留所有权利。
Mesenchymal stem cells (MSCs) are considered to be a promising platform for cell and gene therapy for a variety of diseases. First, in the field of hematopoietic stem cell transplantation, there are two applications of MSCs: 1) the improvement of stem cell engrafting and the acceleration of hematopoietic reconstitution based on the hematopoiesis-supporting ability; and 2) the treatment of severe graft-versus-host disease (GVHD) based on the immunomodulatory ability. Regarding the immunosuppressive ability, we found that nitric oxide (NO) is involved in the MSC-mediated suppression of T cell proliferation. Second, tumor-bearing nude mice were injected with luciferase-expressing MSCs. An in vivo imaging analysis showed the significant accumulation of the MSCs at the site of tumors. The findings suggest that MSCs can be utilized to target metastatic tumors and to deliver anti-cancer molecules locally. As the third application, MSCs may be utilized as a cellular vehicle for protein-supplement gene therapy. When long-term transgene expression is needed, a therapeutic gene should be introduced with a minimal risk of insertional mutagenesis. To this end, site-specific integration into the AAVS 1 locus on the chromosome 19 (19q13.4) by using the integration machinery of adeno-associated virus (AAV) would be particularly valuable. There will be wide-ranging applications of MSCs to frontier medical treatments in the near future. (C) 2008 Elsevier Ltd. All rights reserved.