The Effect of EPO Gene Overexpression on Proliferation and Migration of Mouse Bone Marrow-Derived Mesenchymal Stem Cells

详细信息    查看全文

• 作者：Haihong Lin ; Xinping Luo ; Bo Jin ; Haiming Shi ; Hui Gong
• 关键词：EPO ; Transfection ; MSCs ; Proliferation ; Migration ; Signaling pathway
• 刊名：Cell Biochemistry and Biophysics
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：71
• 期：3
• 页码：1365-1372
• 全文大小：1,384 KB
• 参考文献：1.Sanganalmath, S. K., & Bolli, R. (2013). Cell therapy for heart failure: a comprehensive overview of experimental and clinical studies, current challenges, and future directions. Circulation Research, 113(6), 810-34.View Article PubMed Central PubMed
  2.Chen, Y., Liu, W., Li, W., & Gao, C. (2010). Autologous bone marrow mesenchymal cell transplantation improves left ventricular function in a rabbit model of dilated cardiomyopathy. Experimental and Molecular Pathology, 88(2), 311-15.View Article PubMed
  3.Mu, Y., Cao, G., Zeng, Q., & Li, Y. (2011). Transplantation of induced bone marrow mesenchymal stem cells improves the cardiac function of rabbits with dilated cardiomyopathy via upregulation of vascular endothelial growth factor and its receptors. Experimental Biology and Medicine (Maywood)., 236(9), 1100-107.View Article PubMed
  4.Yu, Q., Li, Q., Na, R., Li, X., Liu, B., Meng, L., et al. (2014). Impact of repeated intravenous bone marrow mesenchymal stem cells infusion on myocardial collagen network remodeling in a rat model of doxorubicin-induced dilated cardiomyopathy. Molecular and Cellular Biochemistry, 387(1-), 279-85.View Article PubMed
  5.Müller-Ehmsen, J., Krausgrill, B., Burst, V., Schenk, K., Neisen, U. C., Fries, J. W., et al. (2006). Effective engraftment but poor mid-term persistence of mononuclear and mesenchymal bone marrow cells in acute and chronic rat myocardial infarction. Journal of Molecular and Cellular Cardiology, 41, 876-84.View Article PubMed
  6.Westenbrink, B. D., Oeseburg, H., Kleijn, L., et al. (2008). Erythropoietin stimulates normal endothelial progenitor cell-mediated endothelial turnover, but attributes to neovascularization only in the presence of local ischemia. Cardiovascular Drugs and Therapy, 22(4), 265-74.View Article PubMed
  7.Wang, Y., Cooke, M. J., Morshead, C. M., et al. (2012). Hydrogel delivery of erythropoietin to the brain for endogenous stem cell stimulation after stroke injury. Biomaterials, 33(9), 2681-692.View Article PubMed
  8.Sanchis-Gomar, F., Garcia-Gimenez, J. L., Pareja-Galeano, H., et al. (2014). Erythropoietin and the heart: physiological effects and the therapeutic perspective. International Journal of Cardiology, 71(2), 116-25.View Article
  9.Chen, L., Qiu, R., & Xu, Q. (2014). Stem cell therapy for ischemic stroke. Journal of Nanoscience and Nanotechnology, 14(1), 976-82.View Article PubMed
  10.Gupta, N. K., Armstrong, E. J., & Parikh, S. A. (2014). The current state of stem cell therapy for peripheral artery disease. Current Cardiology Reports, 16(2), 447.View Article PubMed
  11.Fung, M. E., & Thébaud, B. (2014). Stem cell-based therapy for neonatal lung disease: it is in the juice. Pediatric Research, 75(1-), 2-.View Article PubMed Central PubMed
  12.Strauer, B. E., & Steinhoff, G. (2011). 10?years of intracoronary and intramyocardial bone marrow stem cell therapy of the heart: from the methodological origin to clinical practice. Journal of the American College of Cardiology, 58(11), 1095-104.View Article PubMed
  13.Caplan, A. I., & Correa, D. (2011). The MSC: An injury drugstore. Cell Stem Cell, 9, 11-5.View Article PubMed Central PubMed
  14.Lee, R. H., Pulin, A. A., Seo, M. J., et al. (2009). Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell, 5, 54-3.View Article PubMed Central PubMed
  15.Ortiz, L. A., Dutreil, M., Fattman, C., et al. (2007). Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proceedings of the National Academy of Sciences of the United States of America, 104, 11002-1007.View Article PubMed Central PubMed
  16.Sato, K., Ozaki, K., Oh, I., et al. (2007). Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood, 109, 228-34.View Article PubMed
  17.Xu, J., Qu, J., Cao, L., et al. (2008). Mesenchymal stem cell-based angiopoietin-1gene therapy for acute lung injury induced by lipopolysaccharide in mice. The Journal of Pathology, 214, 472-81.View Article PubMed
  18.Cheng, Z., Ou, L., Zhou, X., et al. (2008). Targeted migration of mesenchymal stem cells modified with CXCR4 gene to infarcted myocardium improves cardiac performance. Molecular Therapy, 16, 571-79.View Article PubMed
  19.Wu, J., Sun, Z., Sun, H. S., et al. (2008). Intravenously administered bone marrow cells migrate to damaged brain tissue and improve neural function in ischemic rats. Cell Transplantation, 16, 993-005.View Article PubMed
  20.Parekkadan, B., & Milwid, J. M. (2010). Mesenchymal stem cells as therapeutics. Annual Review of Biomedical Engineering, 12, 87-17.View Article PubMed Central PubMed
  21.Clifford, D.M., Fisher, S.A., Brunskill, S.J., et al. (2012). Stem cell treatment for acute myocardial infarction. Cochrane Database of Sys
• 作者单位：Haihong Lin (1)
  Xinping Luo (2)
  Bo Jin (2)
  Haiming Shi (2)
  Hui Gong (1)
  
  1. Department of Cardiology, Jinshan Hospital Affiliated to Fudan University, Shanghai, 200433, China
  2. Department of Cardiology, Huashan Hospital Affiliated to Fudan University, Shanghai, 200433, China
  
• 刊物主题：Biochemistry, general; Pharmacology/Toxicology; Biotechnology; Cell Biology; Biophysics and Biological Physics;
• 出版者：Springer US
• ISSN：1559-0283

文摘

The aim of this study is to investigate the effect of erythropoietin (EPO) gene overexpression on proliferation and migration of mouse bone marrow-derived mesenchymal stem cells (MSCs), and to determine the underlying signaling pathway. Mouse MSCs were cultured in vitro and EPO gene was transfected into the 6th generation of MSCs via lentivirus vector. The transfected cells were identified by flow cytometry and the EPO levels in supernatant were measured with ELISA. In addition, cell proliferation was assessed by CCK-8 assay and cell migration was evaluated by Transwell assay. The activation of Akt, ERK1/2, and p38MAPK signaling was detected by western blotting. The lentivirus vector containing EPO was successfully constructed and transfected into MSCs. No remarkable change was found in the cell surface markers after transfection while a significant increase of EPO level in supernatant was noticed in transfected MSCs compared to controls (P?<?0.01). In addition, transfected MSCs showed a significantly enhanced proliferation (P?<?0.01) as well as a notable increase in migration (P?<?0.01) compared to controls. Furthermore, we also found that EPO modification enhanced the phosphorylation of PI3K/Akt and ERK signaling pathway, and suppressed the phosphorylation of p38MAPK without affecting the levels of total Akt, ERK1/2, and p38MAPK in MSCs. After transfection, MSCs secreted more EPO which enhanced the capability of proliferation and migration. Moreover, our results suggested that the enhanced proliferation and migration might be associated with activation of PI3K/Akt and ERK or inhibition of P38MAPK signaling pathway.