Studeny Matus, Marini Frank C, Champlin Richard E, Zompetta Claudia, Fidler Isaiah J, Andreeff Michael
Section of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer Res. 2002 Jul 1;62(13):3603-8.
Molecules that physiologically control cell proliferation are often produced locally in tissues and are rapidly destroyed when they enter circulation. This allows local effects while avoiding interference with other systems. Unfortunately, it also limits the therapeutic use of these molecules via systemic delivery. We here demonstrate that, for the purpose of anticancer therapy, bone marrow-derived mesenchymal stem cells (MSCs) can produce biological agents locally at tumor sites. We show that the tumor microenvironment preferentially promotes the engraftment of MSCs as compared with other tissues. MSCs with forced expression of IFN-beta inhibited the growth of malignant cells in vivo. Importantly, this effect required the integration of MSCs into the tumors and could not be achieved by systemically delivered IFN-beta or by IFN-beta produced by MSCs at a site distant from the tumors. Our results indicate that MSCs may serve as a platform for delivery of biological agents in tumors.
生理上控制细胞增殖的分子通常在组织局部产生，进入循环后会迅速被破坏。这使得它们能够产生局部效应，同时避免干扰其他系统。不幸的是，这也限制了这些分子通过全身给药的治疗用途。我们在此证明，为了进行抗癌治疗，骨髓来源的间充质干细胞（MSCs）可以在肿瘤部位局部产生生物制剂。我们表明，与其他组织相比，肿瘤微环境优先促进MSCs的植入。强制表达IFN-β的MSCs在体内抑制了恶性细胞的生长。重要的是，这种效应需要MSCs整合到肿瘤中，通过全身递送IFN-β或由远离肿瘤部位的MSCs产生的IFN-β无法实现。我们的结果表明，MSCs可能作为肿瘤中生物制剂递送的平台。
