https://scholars.lib.ntu.edu.tw/handle/123456789/468716
標題: | CXCR4 antagonist TG-0054 mobilizes mesenchymal stem cells, attenuates inflammation, and preserves cardiac systolic function in a porcine model of myocardial infarction | 作者: | WAN-TSENG HSU Jui H.-Y. Huang Y.-H. MAO-YUAN SU YEN-WEN WU WEN-YIH TSENG Hsu M.-C. BOR-LUEN CHIANG Wu K.K. CHII-MING LEE |
公開日期: | 2015 | 出版社: | Cognizant Communication Corporation | 卷: | 24 | 期: | 7 | 起(迄)頁: | 1313-1328 | 來源出版物: | Cell Transplantation | 摘要: | Interaction between chemokine stromal cell-derived factor 1 and the CXC chemokine receptor 4 (CXCR4) governs the sequestration and mobilization of bone marrow stem cells. We investigated the therapeutic potential of TG-0054, a novel CXCR4 antagonist, in attenuating cardiac dysfunction after myocardial infarction (MI). In miniature pigs (minipigs), TG-0054 mobilized CD34+CXCR4+, CD133+CXCR4+, and CD271+CXCR4+ cells into peripheral circulation. After isolation and expansion, TG-0054-mobilized CD271+ cells were proved to be mesenchymal stem cells (designated CD271-MSCs) since they had trilineage differentiation potential, surface markers of MSCs, and immunosuppressive effects on allogeneic lymphocyte proliferation. MI was induced in 22 minipigs using balloon occlusion of the left anterior descending coronary artery, followed by intravenous injections of 2.85 mg/kg of TG-0054 or saline at 3 days and 7 days post-MI. Serial MRI analyses revealed that TG-0054 treatment prevented left ventricular (LV) dysfunction at 12 weeks after MI (change of LV ejection fraction from baseline, ?1.0 ± 6.2% in the TG-0054 group versus ?7.9 ± 5.8% in the controls). The preserved cardiac function was accompanied by a significant decrease in the myocardial expression of TNF-α, IL-1β, and IL-6 at 7 days post-MI. Moreover, the plasma levels of TNF-α, IL-1β, and IL-6 were persistently suppressed by the TG-0054 treatment. Infusion of TG-0054-mobilized CD271-MSCs reduced both myocardial and plasma cytokine levels in a pattern, which is temporally correlated with TG-0054 treatment. This study demonstrated that TG-0054 improves the impaired LV contractility following MI, at least in part, by mobilizing MSCs to attenuate the postinfarction inflammation. This insight may facilitate exploring novel stem cell-based therapy for treating post-MI heart failure. ? 2015 Cognizant Comm. Corp. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84937432800&doi=10.3727%2f096368914X681739&partnerID=40&md5=6f2c9f461395591a282229d22076793d https://scholars.lib.ntu.edu.tw/handle/123456789/468716 |
ISSN: | 0963-6897 | DOI: | 10.3727/096368914X681739 | SDG/關鍵字: | CD133 antigen; CD34 antigen; chemokine receptor CXCR4; chemokine receptor CXCR4 antagonist; interleukin 1beta; interleukin 6; tg 0054; tumor necrosis factor alpha; unclassified drug; chemokine receptor CXCR4; adult; animal cell; animal experiment; animal model; animal tissue; Article; balloon occlusion; cell differentiation; cell isolation; cell lineage; controlled study; female; heart function; heart infarction; heart left ventricle contractility; heart left ventricle ejection fraction; human; immunomodulation; inflammation; left anterior descending coronary artery; lymphocyte proliferation; male; mesenchymal stem cell; minipig; nonhuman; nuclear magnetic resonance imaging; peripheral circulation; priority journal; protein expression; single drug dose; stem cell expansion; stem cell mobilization; animal; antagonists and inhibitors; cytology; disease model; heart left ventricle function; inflammation; mesenchymal stem cell transplantation; mesenchymal stroma cell; metabolism; Myocardial Infarction; physiology; pig; porcine reproductive and respiratory syndrome; Suidae; Sus; Animals; Disease Models, Animal; Immunomodulation; Inflammation; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells; Myocardial Infarction; Porcine Reproductive and Respiratory Syndrome; Receptors, CXCR4; Swine; Ventricular Function, Left |
顯示於: | 醫療器材與醫學影像研究所 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。