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间充质干细胞作为靶向肿瘤基质的治疗性输送载体。

Mesenchymal stem cells as therapeutic delivery vehicles targeting tumor stroma.

机构信息

Telomere and Aging Group, Institute of Regional Health Research (IRS), Southern Denmark University, Vejle, Denmark.

出版信息

Cancer Biother Radiopharm. 2011 Dec;26(6):767-73. doi: 10.1089/cbr.2011.1024. Epub 2011 Aug 30.

Abstract

The field of stem cell biology continues to evolve by characterization of further types of stem cells and by exploring their therapeutic potential for experimental and clinical applications. Human mesenchymal stem cells (hMSCs) are one of the most promising candidates simply because of their easiness of both ex vivo expansion in culture dishes and genetic manipulation. Despite many extensive isolation and expansion studies, relatively little has been done with regard to hMSCs' therapeutic potential. Although clinical trials using hMSCs are underway, their use in cancer therapy still needs better understanding and in vivo supporting data. The homing ability of hMSCs was investigated by creating a human xenograft model by transplanting an ovarian cancer cell line into immunocompromised mice. Then, genetically engineered hMSC-telo1 cells were injected through the tail vein and the contribution and distribution of hMSCs to the tumor stroma were investigated by immunohistochemistry and PCR specific to the telomerase gene. Results show that exogenously administered hMSCs preferentially home, engraft, and proliferate at tumor sites and contribute to the population of stromal fibroblasts. In conclusion, this study provides support for the capacity of hMSCs to home to tumor site and serve as a delivery platform for chemotherapeutic agents.

摘要

干细胞生物学领域通过对更多类型的干细胞进行特征描述,并探索其在实验和临床应用中的治疗潜力,不断发展。人骨髓间充质干细胞(hMSC)是最有前途的候选者之一,这仅仅是因为它们在体外培养皿中易于扩增和遗传操作。尽管已经进行了许多广泛的分离和扩增研究,但在 hMSC 的治疗潜力方面相对较少。尽管正在进行使用 hMSC 的临床试验,但它们在癌症治疗中的应用仍需要更好的理解和体内支持数据。通过将卵巢癌细胞系移植到免疫功能低下的小鼠中,创建了人异种移植模型,从而研究了 hMSC 的归巢能力。然后,通过尾静脉注射基因工程 hMSC-telo1 细胞,并通过针对端粒酶基因的免疫组织化学和 PCR 特异性研究 hMSC 对肿瘤基质的贡献和分布。结果表明,外源性给予的 hMSC 优先归巢、植入并在肿瘤部位增殖,并有助于基质成纤维细胞的群体。总之,这项研究为 hMSC 向肿瘤部位归巢并作为化疗药物的递送平台的能力提供了支持。

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