Department of Anatomy & Physiology, College of Veterinary Medicine, Kansas State University, 1600 Denison Ave, Manhattan, KS 66506, USA.
Lung Cancer. 2010 Oct;70(1):28-36. doi: 10.1016/j.lungcan.2010.01.003.
Mesenchymal stem cells derived from the human umbilical cord matrix (hUCMSCs) have great potential for therapeutic use for multiple diseases. The strategy that uses therapeutic gene-transfected hUCMSCs as cellular vehicles for targeted biologic agent delivery has solved the problem of short half-life or excessive toxicity of biological agent(s) in vivo. Interferon-beta (IFN-beta) has demonstrated a potent antitumor effect on many types of cancer cell lines in vivo. The aim of this study was to determine the anti-cancer effect of IFN-beta gene-transfected hUCMSCs (IFN-beta-hUCMSCs) on cells derived from bronchioloalveolar carcinoma, a subset of lung adenocarcinoma that is difficult to treat. The co-culture of a small number of IFN-beta-hUCMSCs with the human bronchioloalveolar carcinoma cell lines H358 or SW1573 significantly inhibited growth of both types of carcinoma cell lines. The culture medium conditioned by these cells also significantly attenuated the growth of both carcinoma cells, but this attenuation was abolished by adding anti-IFN-beta antibody. Finally, systemic administration of IFN-beta-hUCMSCs through the tail vein markedly attenuated growth of orthotopic H358 bronchioloalveolar carcinoma xenografts in SCID mice by increasing apoptosis. These results clearly indicate that IFN-beta-hUCMSCs caused cell death of bronchioloalveolar carcinoma cells through IFN-beta production, thereby attenuating tumor growth in vivo. These results indicate that IFN-beta-hUCMSCs are a powerful anti-cancer cytotherapeutic tool for bronchioloalveolar carcinoma.
人脐带基质来源的间充质干细胞（hUCMSCs）在治疗多种疾病方面具有巨大的应用潜力。将治疗基因转染的 hUCMSCs 作为靶向生物制剂传递的细胞载体的策略解决了生物制剂（s）在体内半衰期短或毒性过大的问题。干扰素-β（IFN-β）已在体内证明对许多类型的癌细胞系具有强大的抗肿瘤作用。本研究旨在确定 IFN-β 基因转染的 hUCMSCs（IFN-β-hUCMSCs）对难以治疗的肺腺癌亚类——细支气管肺泡癌细胞的抗癌作用。少量 IFN-β-hUCMSCs 与人类细支气管肺泡癌细胞系 H358 或 SW1573 的共培养显著抑制了这两种癌细胞系的生长。这些细胞的条件培养基也显著减弱了两种癌细胞的生长，但添加抗 IFN-β 抗体可消除这种减弱作用。最后，通过尾静脉系统给予 IFN-β-hUCMSCs 可通过增加细胞凋亡明显减弱 SCID 小鼠原位 H358 细支气管肺泡癌异种移植物的生长。这些结果清楚地表明，IFN-β-hUCMSCs 通过产生 IFN-β 导致细支气管肺泡癌细胞死亡，从而减轻体内肿瘤生长。这些结果表明，IFN-β-hUCMSCs 是治疗细支气管肺泡癌的强大抗癌细胞治疗工具。
