Human umbilical cord matrix-derived stem cells expressing interferon-β gene significantly attenuate bronchioloalveolar carcinoma xenografts in SCID mice

被引:76
作者
Matsuzuka, Takaya [1 ]
Rachakatla, Raja Shekar [1 ]
Doi, Chiyo [1 ]
Maurya, Dharmendra Kumar [1 ]
Ohta, Naomi [1 ]
Kawabata, Atsushi [1 ]
Pyle, Marla M. [1 ]
Pickel, Lara [1 ]
Reischman, Jennifer [1 ]
Marini, Frank [2 ]
Troyer, Deryl [1 ]
Tamura, Masaaki [1 ]
机构
[1] Kansas State Univ, Coll Vet Med, Dept Anat & Physiol, Manhattan, KS 66506 USA
[2] Univ Texas MD Anderson Canc Ctr, Dept Blood & Marrow Transplantat, Houston, TX 77030 USA
关键词
Bronchioloalveolar carcinoma; H358; cells; SW1573; Interferon-beta; Stem cell therapy; Umbilical cord matrix-derived stem cells; Xenografts; SCID mice; GROWTH-FACTOR; FAS LIGAND; IFN-BETA; IN-VIVO; THERAPY; CANCER; APOPTOSIS; LINES; GLIOMA; INDUCTION;
D O I
10.1016/j.lungcan.2010.01.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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-hUCMSC5 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-hUCMSC5 are a powerful anti-cancer cytotherapeutic tool for bronchioloalveolar carcinoma. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:28 / 36
页数:9
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