Therapeutic potential of mesenchymal stem cells producing interferon-alpha in a mouse melanoma lung metastasis model.
Therapeutic potential of mesenchymal stem cells producing interferon-alpha in a mouse melanoma lung metastasis model.
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DOI：
10.1634/stemcells.2008-0084
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发表时间：
2008-09
期刊：
影响因子：
--
通讯作者：
Ponnazhagan S
中科院分区：
文献类型：
--
作者：
Ren C;Kumar S;Chanda D;Chen J;Mountz JD;Ponnazhagan S
成体干细胞代表了基于细胞的癌症治疗的潜在来源。本研究评价了经基因修饰表达干扰素（IFN）-α的骨髓间充质干细胞（MSC）治疗免疫活性小鼠转移性黑色素瘤肺转移的潜力。用重组腺相关病毒6型载体（rAAV）转染小鼠骨髓间充质干细胞（MSC）。在体内研究之前，确认来自rAAV转导的MSC的转基因蛋白的表达和生物活性。通过将B16 F10细胞静脉注射到8周龄C57 BL/6小鼠中来建立黑色素瘤的肺转移模型。10天后，静脉内注射用rAAV-IFN-α或GFP转导的MSC。处死一组小鼠以确定在较早时间点的治疗效果，并观察另一组小鼠的长期存活。结果表明，全身施用产生IFN-α的MSC减少了B16 F10黑素瘤细胞的生长并显著延长了存活。免疫组织化学分析显示，MSC-IFN-α治疗动物的肿瘤细胞凋亡增加，增殖和血管减少。这些数据证明了组成型产生IFN-α的成体MSC减少黑色素瘤肺转移生长的潜力。
Adult stem cells represent a potential source for cell-based therapy of cancer. The present study evaluated the potential of bone marrow derived mesenchymal stem cells (MSC), genetically modified to express interferon (IFN)-α, for the treatment of lung metastasis in an immunocompetent mouse model of metastatic melanoma. A recombinant adeno-associated virus 6 vector (rAAV) encoding IFN-α was used to transduce mouse bone marrow-derived MSC ex vivo. Expression and bioactivity of the transgenic protein from rAAV-transduced MSC were confirmed prior to in vivo studies. A lung metastasis model of melanoma was developed by intravenous injection of B16F10 cells into 8-week-old C57BL/6 mice. Ten days later, MSC, transduced with rAAV-IFN-α or GFP were intravenously injected. One cohort of mice was sacrificed to determine the effects of the therapy at an earlier time point and another cohort was observed for long-term survival. Results indicated that systemic administration of MSC producing IFN-α reduced the growth of B16F10 melanoma cells and significantly prolonged survival. Immunohistochemistry analysis of the tumors from MSC-IFN-α treated animals indicated an increase in apoptosis and decrease in proliferation and blood vasculature. These data demonstrate the potential of adult MSC, constitutively producing IFN-α, to reduce the growth of lung metastasis in melanoma.
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DOI：
10.1186/bcr554
发表时间：
2003
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Ben-Baruch A
通讯作者：
Ben-Baruch A
影响因子：
11.2
作者：
Nakamizo, A;Marini, F;Lang, FF
通讯作者：
Lang, FF
影响因子：
2.6
作者：
Conget, PA;Minguell, JJ
通讯作者：
Minguell, JJ
影响因子：
4.8
作者：
Koç, ON;Day, J;Krivit, W
通讯作者：
Krivit, W
影响因子：
2.2
作者：
Conill, Carlos;Jorcano, Sandra;Castel, Teresa
通讯作者：
Castel, Teresa