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人类和小鼠间充质干细胞均可促进乳腺癌转移。

Both human and mouse mesenchymal stem cells promote breast cancer metastasis.

作者信息

Albarenque Stella Maris, Zwacka Ralf Michael, Mohr Andrea

机构信息

National University of Ireland, Galway, National Centre for Biomedical Engineering Science, Molecular Therapeutics Group, Galway, Ireland.

出版信息

Stem Cell Res. 2011 Sep;7(2):163-71. doi: 10.1016/j.scr.2011.05.002. Epub 2011 May 10.

DOI:10.1016/j.scr.2011.05.002
PMID:21763624
Abstract

Cell therapy has the potential to offer novel treatment modalities for a number of diseases including cancer, and stem cells and in particular mesenchymal stem cells (MSCs) have been experimentally used to deliver therapeutic transgenes. However, conflicting reports have on the one side found that human MSCs can promote metastasis, while on the other hand other studies have shown that MSCs can stall the growth of metastatic lesions. In order to clarify the role of MSCs in metastasis development, we tested whether murine MSCs would behave similarly to human cells in mice. We found that the tissue distribution of human and mouse MSCs was nearly identical after intravenous injection. In mice with MDA-MB-231 mammary carcinoma xenografts we found that a fraction of MSCs infiltrated the primary tumor mass, but that the general tissue distribution of MSCs was unaffected by the tumor-burden. About half of the tumor-burdened animals that were treated with murine and human MSCs, respectively, harbored metastatic lesions with only 17% of controls showing metastatic nodules. Hence, both human and mouse MSCs possess metastasis-promoting activity raising concerns about the safe use of MSCs, but at the same time making the use of murine transgenic model systems feasible to study the role of MSCs in metastasis development and possibly finding ways of using them safely as cell therapeutic vehicles.

摘要

细胞疗法有潜力为包括癌症在内的多种疾病提供新的治疗方式,干细胞尤其是间充质干细胞(MSCs)已被用于实验性递送治疗性转基因。然而,相互矛盾的报道一方面发现人类间充质干细胞可促进转移,而另一方面其他研究表明间充质干细胞可抑制转移灶的生长。为了阐明间充质干细胞在转移发展中的作用,我们测试了小鼠间充质干细胞在小鼠体内的行为是否与人类细胞相似。我们发现静脉注射后,人类和小鼠间充质干细胞的组织分布几乎相同。在患有MDA-MB-231乳腺癌异种移植瘤的小鼠中,我们发现一部分间充质干细胞浸润了原发性肿瘤块,但间充质干细胞的总体组织分布不受肿瘤负荷的影响。分别用小鼠和人类间充质干细胞治疗的约一半有肿瘤负荷的动物出现了转移灶,而对照组只有17%出现转移结节。因此,人类和小鼠间充质干细胞都具有促进转移的活性,这引发了对间充质干细胞安全使用的担忧,但同时也使得利用小鼠转基因模型系统来研究间充质干细胞在转移发展中的作用并可能找到安全使用它们作为细胞治疗载体的方法成为可能。

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