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  • Meifeng Xu, PhD
  • Research Associate Professor
  •  
  • UC Cardiovascular Diseases Center
  • Phone: (513) 558-4725
  • meifeng.xu@uc.edu

Specialty/Interest:

  • My research interest is focused on two areas:

    The first is on the molecular and cellular mechanisms of myocardial ischemic injury, with the primary endpoint of identifying therapies that prevent cell damage/death in the ischemic heart. Significant protection of cardiomyocytes against ischemic injury is possible with ischemic or pharmacological preconditioning.

    The second area of interest is in the cell based therapy. Following an ischemic event, damaged muscle is replaced with scar tissue, which impairs the pump function of the heart. Therefore my current investigation is exploiting the potential of bone marrow derived mesenchymal stem cells (BMSC) in regenerating the dead myocardium and protecting the ischemic areas through paracrine factors. We found that mobilized bone marrow stem cells, are superior to the niched BMSC in the repair of ischemic myocardium due to upregulation of GATA-4 which results in an enhanced differentiation and release of multiple paracrine factors. Therefore, my laboratory has developed a novel approach of combining stem cell transplantation with therapeutic gene delivery via genetic modulation of the donor cells prior to transplantation. The overexpression of GATA-4 in BMSC not only promotes BMSC and myocyte survival but also regulates expression of several bioactive molecules, including miRNAs. Currently, we are testing the new concepts as how stem cells carry and transfer miRNAs and/or genes and other bioactive molecules to neighboring cells where cytoprotection and regeneration of injury tissue occur. Our study has indicated that gap junctions and exosomesare involved in transfer of bioactive molecules among different type of cells. Understanding of these innovative ideas would be of great importance in designing cell based therapy against ischemic myocardium.   

    Education/Credentials:

  • MD: Suzhou Medical College, 1982
  • M.Sc.: Suzhou Medical College, 1989
  • PhD: The Hong Kong Polytechnic University, 1999

Research Grants:

  • R01 HL083236 National Heart, Lung and Blood Institute. Mobilized Stem Cells in Cardiomyogenesis and Angiogenesis, PI, 003577-001.
  • R01 HL089824 National Heart, Lung and Blood Institute. A Novel Approach to Enhance Cell Therapy for Myocardial Regeneration, Collaborator, 005723-001.
  • R01 HL105176 National Heart, Lung and Blood Institute. Wnt11 Signaling in Stem Cell Survival and Cardiac Regeneration, PI, 007099-001.
  • R01 HL110740 National Heart, Lung and Blood Institute. iPS Cells-Derived Progenitor Cells for Angiomyogenesis, Collaborator, Active.
  • R01HL114654 National Heart, Lung and Blood Institute. MicroRNA as Mediators of Angiogenesis and Ischemic Myocardial Repair, PI, Active.

Peer Reviewed Publications (in chronological order):

  • Xu M, Millard RW, Ashraf M (2012). Role of GATA-4 in Differentiation and Survival of Bone Marrow Mesenchymal Stem Cells . Prog Mol Biol Transl Sci. , 111 , 217-241.
  • Zuo S, Jones WK, Li H, He Z, Pasha Z, Yang Y, Wang YG, Fan GC, Ashraf M, Xu M (2012). Paracrine Effect of Wnt11 Overexpressing Mesenchymal Stem Cells on Ischemic Injury . Stem Cells Dev , 21 , 598-608.
  • Huang W, Wang T, Zhang D, Zhao T, Dai B, Ashraf A, Wang X, Xu M, Millard RW, Fan GC, Ashraf M, Yu XY, Wang YG (2012). Mesenchymal Stem Cells Overexpressing CXCR4 Attenuate Remodeling of Post-myocardial Infarction by Releasing Matrix Metalloproteinase-9 . Stem Cells Dev , 21 , 778-89.
  • Zuo, S., Jones, W. K., Li, H., He, Z., Pasha, Z., Yang, Y., Wang, Y., Fan, G., Ashraf, M., & Xu, M. (2011). Paracrine Effect of Wnt11 Overexpressing Mesenchymal Stem Cells on Ischemic Injury . Stem Cells and Development.
  • He, Z., Li, H., Zuo, S., Pasha, Z., Wang, Y., Yang, Y., Jiang, W., Ashraf, M., & Xu, M. (2011). Transduction of Wnt11 Promotes Mesenchymal Stem Cell Transdifferentiation into Cardiac Phenotypes . Stem Cells and Development.
  • Dai B, Huang W, Xu M, Millard RW, Gao MH, Hammond HK, Menick DR, Ashraf M, Wang Y (2011). Reduced Collagen Deposition in Infarcted Myocardium Facilitates Induced Pluripotent Stem Cells (iPSC) Engraftment and Angiomyogenesis for Improvement of Left Ventricular Function . J Am Coll Cardiol , 58 , 2118-27 .
  • Li H, Zuo S, Pasha Z, Yu B, He Z, Wang Y, Yang X, Ashraf M, Xu M (2011). GATA-4 promotes myocardial transdifferentiation of mesenchymal stromal cells via up-regulating IGFBP-4 . Cytotherapy , 13 , 1057-1065.
  • Li, H., Zuo, S., He, Z., Yang, Y., Pasha, Z., Wang, Y., & Xu, M. (2010). Paracrine factors released by GATA-4 overexpressed mesenchymal stem cells increase angiogenesis and cell survival . American Journal of Physiology. Heart and Circulatory Physiology , 299 (6) , H1772-81.
  • Huang, W., Zhang, D., Millard, R. W., Wang, T., Zhao, T., Fan, G., Ashraf, A., Xu, M., Ashraf, M., & Wang, Y. (2010). Gene manipulated peritoneal cell patch repairs infarcted myocardium . Journal of Molecular and Cellular Cardiology , 48 (4) , 702-12.
  • Wang, X., Zhao, T., Huang, W., Wang, T., Qian, J., Xu, M., Kranias, E. G., Wang, Y., & Fan, G. (2009). Hsp20-engineered mesenchymal stem cells are resistant to oxidative stress via enhanced activation of Akt and increased secretion of growth factors . Stem Cells (Dayton, Ohio) , 27 (12) , 3021-31.
  • Dai, Y., Ashraf, M., Zuo, S., Uemura, R., Dai, Y., Wang, Y., Haider, H. K., Li, T., & Xu, M. (2008). Mobilized bone marrow progenitor cells serve as donors of cytoprotective genes for cardiac repair . Journal of Molecular and Cellular Cardiology , 44 (3) , 607-17.
  • Zhang, D., Fan, G., Zhou, X., Zhao, T., Pasha, Z., Xu, M., Zhu, Y., Ashraf, M., & Wang, Y. (2008). Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium . Journal of Molecular and Cellular Cardiology , 44 (2) , 281-92.
  • Dai, Y., Xu, M., Wang, Y., Pasha, Z., Li, T., & Ashraf, M. (2007). HIF-1alpha induced-VEGF overexpression in bone marrow stem cells protects cardiomyocytes against ischemia . Journal of Molecular and Cellular Cardiology , 42 (6) , 1036-44.
  • Xu, M., Uemura, R., Dai, Y., Wang, Y., Pasha, Z., & Ashraf, M. (2007). In vitro and in vivo effects of bone marrow stem cells on cardiac structure and function . Journal of Molecular and Cellular Cardiology , 42 (2) , 441-8.
  • Uemura, R., Xu, M., Ahmad, N., & Ashraf, M. (2006). Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling . Circulation Research , 98 (11) , 1414-21.
  • Wang, Y., Haider, H. K., Ahmad, N., Xu, M., Ge, R., & Ashraf, M. (2006). Combining pharmacological mobilization with intramyocardial delivery of bone marrow cells over-expressing VEGF is more effective for cardiac repair . Journal of Molecular and Cellular Cardiology , 40 (5) , 736-45.
  • Xu, M., Wani, M., Dai, Y., Wang, J., Yan, M., Ayub, A., & Ashraf, M. (2004). Differentiation of bone marrow stromal cells into the cardiac phenotype requires intercellular communication with myocytes . Circulation , 110 (17) , 2658-65.
  • Xu M, Wani M, Dai Y, Wang J, Yan M, Ashraf M (2004). Differentiation of bone marrow stromal cells into cardiac phenotype requires intercellular communication with myocytes . Circulation , 110 , 2658-65.
  • Kudo, M., Wang, Y., Wani, M. A., Xu, M., Ayub, A., & Ashraf, M. (2003). (In Press). Implantation of bone marrow stem cells reduces the infarction and fibrosis in ischemic mouse heart. . Journal of Molecular and Cellular Cardiology , 35 (9) , 1113-9.
  • Kudo, M., Wang, Y., Xu, M., Ayub, A., & Ashraf, M. (2002). Adenosine A(1) receptor mediates late preconditioning via activation of PKC-delta signaling pathway . American Journal of Physiology. Heart and Circulatory Physiology , 283 (1) , H296-301.
  • Xu, M., & Ashraf, M. (2002). (In Press). Melatonin protection against lethal myocyte injury induced by doxorubicin as reflected by effects on mitochondrial membrane potential. . Journal of Molecular and Cellular Cardiology , 34 (1) , 75-9.