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近日,国际学术期刊Oncogene在线发表了中科院上海生命科学研究院健康科学研究所时玉舫研究组题为Interferon-α-secreting mesenchymal stem cells exert potent antitumor effect in vivo的研究论文,报道了间充质干细胞(Mesenchymal stem cells, MSCs)作为抗肿瘤药物载体在肿瘤靶向治疗中的重要作用及机制。2 ^7 `( l# l1 Y2 Z/ \8 u* f
MSCs作为干细胞的一种,在机体大部分组织中广泛存在,并且较易获得。除了自我更新和多向分化潜能外,MSCs还具有免疫调节作用以及向损伤部位迁移的特性。由于肿瘤被认为是“永不愈合的创伤”,因此MSCs成为实施肿瘤靶向治疗的理想载体。一型干扰素(Interferon-a, IFNa )是在临床上广泛应用的抗肿瘤药物,由于半衰期较短,它在治疗肿瘤时的应用剂量往往较高,给病人带来严重副作用。博士研究生徐春亮等成功构建了能高效、持续分泌功能性IFNa的MSCs(MSC-IFNa),并利用该细胞进行黑色素瘤治疗。研究表明,MSC-IFNa可以在体内肿瘤部位存活超过两周,并且MSC-IFNa可以极为有效地抑制B16黑色素瘤细胞的增殖,促进黑色素瘤细胞凋亡,其抗肿瘤机制与NK细胞和CD8+T细胞相关。值得注意的是,MSC-IFNa产生的IFNa尽管远低于临床应用剂量,但其治疗效果却明显优于高剂量IFNa的治疗效果。该研究表明,MSCs是一个理想的肿瘤靶向治疗及药物缓释载体,为临床上治疗肿瘤提供了重要参考。
% v( B8 |" u7 d ~7 b; N该研究得到了国家科技部、中国科学院战略性先导科技专项、国家自然科学基金委及上海市科委的资助。(生物谷Bioon.com)! |% k% l! V4 n$ @" L- U
生物谷推荐的英文摘要4 d) e* [4 ?2 d2 c% r% J/ ^% N
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Oncogene doi: 10.1038/onc.2013.458% k/ P( l$ e* o
Interferon-α-secreting mesenchymal stem cells exert potent antitumor effect in vivo.: [# Z/ H+ b& J
Xu C, Lin L, Cao G, Chen Q, Shou P, Huang Y, Han Y, Wang Y, Shi Y.0 q6 o3 \! o& V4 i# v
Mesenchymal stem cells (MSCs) are a kind of adult stem cells that can be isolated easily from bone marrow, adipose tissue, umbilical cord and many other tissues. MSCs have been shown to specifically migrate to inflammatory sites, including tumors, and hold great promise as tumor-specific vectors to deliver antitumor agents. Interferon-α (IFNα) has been used in clinic to treat various types of tumors; however, because of its short half-life, significant therapeutic effects require high doses that often results in serious side effects. Here, we tested whether MSCs continuingly secreting IFNα can exert a persistent antitumor effect and eliminate the side effects associated with high clinical doses of recombinant IFNα. We found that even a small number of IFNα-secreting MSCs could potently halt B16 tumor growth in vivo. The antitumor activity of IFNα-secreting MSCs was largely abolished in immunodeficient mice, an effect largely attributed to natural killer cells and CD8+ T cells. Therefore, IFNα-secreting MSCs provide an innovative strategy for tumor therapy.
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