Meifeng Xu
Meifeng Xu, MSc, MD, PhD
Associate Professor of Pathology and Laboratory Medicine

University of Cincinnati Medical Center
USA

Education

1995-1999 Ph.D Biological Sciences The Hong Kong Polytechnic University, Hong Kong, P R China
1986-1989 M.Sc Pharmacology Suzhou Medical College, P R China
1977-1982 M.D. Medicine Suzhou Medical College, P R China

 

Biography

 

Research Interest

The research in our laboratory is focused on cell therapy to regenerate the damaged myocardium and restore cardiac function following a myocardial infarction. We use a combination of gene profiling, tissue engineering, physiological testing, and molecular imaging techniques to investigate whether the cardiac regenerative capacity of stem cells is associated with their survival, proliferation, and/or differentiation. We have obtained substantial expertise in this field, and have published our findings in peer-reviewed journals, including JACC, JMCC, Circulation, Cir Res, Stem Cell, Stem Cells and Development, AJP, and etc. We have engineered bone marrow derived mesenchymal stem cells (MSCs) carrying different genes, e.g., Wnt11, GATA-4, etc. to increase the capacity of stem cells to regenerate ischemic myocardium.

MSC preprogrammed to overexpress GATA-4 (MSCGATA-4) can significantly accelerate repair of ischemic heart tissue. We have demonstrated that paracrine effect plays a critical role in MSCGATA-4 mediated cardiac regeneration. Extracellular vesicles (EVs), including microvesicles (MVs) and exosomes (EXO), have been identified as the paracrine factors secreted by MSCs. One of our present research programs is to characterize EVs that are secreted from MSCGATA-4, and to elucidate the molecular processes of their biogenesis and uptake. We will also investigate the molecular basis for their efficacy in reducing tissue injury in animal models of myocardial ischemia, stroke and other diseases. This research will provide the platform from which to translate our research findings into clinical applications.

Professional Activities:

09/12- Present Associate Prof Department of Pathology and Laboratory Medicine University of Cincinnati
08/06 -- 08/12 Assistant Prof Department of Pathology and Laboratory Medicine University of Cincinnati
01/03 – 07/06 Res. Instructor Department of Pathology and Laboratory Medicine University of Cincinnati
07/99 – 12/02 Postdoctoral fellow Department of Pathology and Laboratory Medicine University of Cincinnati
03/95 – 06/99 Associate Professor Dept. Of Pharmacology Suzhou Medical College, P R China
11/89 – 02/95 Lecturer Dept. Of Pharmacology Suzhou Medical College, P R China
01/83 – 10/89 Assistant Professor Dept. Of Pharmacology Suzhou Medical College, P R China

 

Publications

  1. Yu B, Yang Y, Liu H, Gong M, Millard RW, Wang Y, Ashraf M, Xu M. Clusterin/Akt up-regulation is critical for GATA-4 mediated cytoprotection of mesenchymal stem cells against ischemia injury. PLoS One. 2016 Mar 10;11(3):e0151542. doi: 10.1371/journal.pone.0151542. eCollection 2016. PMID: 26962868
  2. Yang H, Borg TK, Ma Z, Xu M, Wetzel G, Saraf LV, Markwald R, Runyan RB, Gao BZ. Biochip-based study of unidirectional mitochondrial transfer from stem cells to myocytes via tunneling nanotubes.Biofabrication. 2016 Feb 4;8(1):015012. doi: 10.1088/1758-5090/8/1/015012. (PMID: 26844857)
  3. Okada M, Kim HW, Matsu-Ura K, Wang YG, Xu M, Ashraf M.Abrogation of Age-Induced MicroRNA-195 Rejuvenates the Senescent Mesenchymal Stem Cells by Reactivating Telomerase.Stem Cells. 2015 Sep 21. doi: 10.1002/stem.2211. [Epub ahead of print](PMID:26390028)
  4. Kang K, Ma R, CaiW, Huang W, Paul C, Liang J, Wang Y, Zhao T, Kim HW, Xu M, Millard R, Wen Z and Wang Y. Exosomes Secreted From CXCR4 Overexpressing Mesenchymal Stem Cells Promotes Cardioprotection via Akt Signaling Pathway Following Myocardial Infarction," Stem cell International. 01/2015; 2015:1-14. DOI: 10.1155/2015/659890
  5. Cai WF, Kang K, Huang W, Liang JL, Feng YL, Liu GS, Chang H, Wen ZL, Paul C, Xu M, Millard RW, Wang Y.CXCR4 attenuates cardiomyocytes mitochondrial dysfunction to resist ischaemia-reperfusion injury. J Cell Mol Med. 2015 Mar 30. doi: 10.1111/jcmm.12554. [Epub ahead of print](PMID:25824297)
  6. Yu B,Kim HW, Gong M, Wang J, Millard RW, Wang Y, Ashraf M, Xu M.Exosomes secreted from GATA-4 overexpressing mesenchymal stem cells serve as a reservoir of anti-apoptotic microRNAs for cardioprotection. International Journal of Cardiology.2015; 182: 349-360; doi:10.1016/j.ijcard.2014.12.043. (PMID:25590961)
  7. Wang Y, Huang W, Liang J, Wen Z, Chang D, Kang K, Wang J, Xu M,Millard RW, Wang Y.Suicide Gene-Mediated Sequencing Ablation Revealed the Potential Therapeutic Mechanism of Induced Pluripotent Stem Cell-Derived Cardiovascular Cell Patch Post-Myocardial Infarction. Antioxid Redox Signal.2014;Dec 1;21(16):2177-91. 2014; Aug 13. [Epub ahead of print] (PMID:24787391)
  8. Liu H, Chen R, Yang H, Qin W, Borg TK, Dean D, Xu M, Gao BZ.Enzyme-etching technique to fabricate micropatterns of aligned collagen fibrils. Biotechnol Lett. 2014;36(6):1245-52.(PMID:24562408)
  9. Gong M, Yu B,Wang Y, Xu M. Bone Marrow Rejuvenation– An Excellent Potential Therapy for Age-Related Endothelial Dysfunction. Circulation Journal, 2013;77(12):2886-8 (PMID:24132244).
  10. Ma Z, Liu Q, Yang H, Runyan RB, Eisenberg CA, Xu M, Borg TK, Markwald R, Wang Y, Gao BZ. Laser patterning for the study of MSC cardiogenic differentiation at the single-cell level. Light Sci Appl. 2013;2. pii: 68.(PMID:24527266)
  11. Yu B,Gong M, He Z, Wang Y, Millard RW, Ashraf M, Xu M. Enhanced mesenchymal stem cell survival induced by GATA-4 overexpression is partially mediated by regulation of the miR-15 family.Int J. Biochem-Cell Biology2013;45(12):2724-35(PMID:24070634).
  12. Yu B,Gong M, Wang Y, Millard RW, Yang Y, Ashraf M, Xu M. Cardiomyocyte Protection by GATA-4 Gene Engineered Mesenchymal Stem CellsIs Partially Mediated by Translocation of miR-221inMicrovesicles. PLoS One2013;8:e73304. doi: 10.1371/journal.pone.0073304(PMID:24015301).
  13. Huang W, Dai B, Wen Z, Millard RW, Yu XY, Luther K, Xu M, Zhao TC, Yang HT, Qi Z, Lasance K, Ashraf M, Wang Y.Molecular Strategy to Reduce In Vivo Collagen Barrier Promotes Entry of NCX1 Positive Inducible Pluripotent Stem Cells (iPSC(NCX1+)) into Ischemic (or Injured) Myocardium.PLoS One. 2013;8:e70023. doi: 10.1371/journal.pone.0070023(PMID: 23990893).
  14. Ma Z, Yang H, Liu H, Xu M, Runyan RB, Eisenberg CA, Markwald RR, Borg TK, Gao BZ.Mesenchymal stem cell-cardiomyocyte interactions under defined contact modes on laser-patterned biochips. PLoS One.2013;8(2):e56554. doi: 10.1371/journal.pone.0056554. Epub 2013 Feb 13. (PMID: 23418583).
  15. Liu H, Shao Y, Qin W, Runyan RB, Xu M, Ma Z, Borg TK, Markwald R, Gao BZ. Myosin filament assembly onto myofibrils in live neonatal cardiomyocytes observed by TPEF-SHG microscopy. Cardiovasc Res.2013 Feb 1;97(2):262-70, (PMID: 23118131).
  16. Ma Z, Liu Q, Liu H, Yang H, Yun JX, Xu M, Eisenberg CA, Borg TK, Markwald R, Gao BZ. Cardiogenic Regulation of Stem-Cell Electrical Properties in a Laser-Patterned Biochip. Cell MolBioeng. 2012; 5:327-336. (PMID: 23139730).
  17. Ma Z, Liu Q, Liu H, Yang H, Yun JX, Eisenberg C, Borg TK, Xu M, Gao BZ. Laser-patterned stem-cell bridges in a cardiac muscle model for on-chip electrical conductivity analyses. Lab Chip. 2012; 12: 566-73, (PMID: 22170399).
  18. Liang J, Huang W, Yu X, Ashraf A, Wary KK, Xu M, Millard RW, Ashraf M, Wang Y. Suicide Gene Reveals the Myocardial Neovascularization Role of Mesenchymal Stem Cells Overexpressing CXCR4 (MSC(CXCR4)). PLoS One. 2012;7(9):e46158, (PMID: 23029422).
  19. Xu M, Millard RW, Ashraf M.  Role of GATA-4 in Differentiation and Survival of Bone Marrow Mesenchymal Stem Cells. (Review) ProgMolBiolTransl Sci. 2012; 111:217-41 (PMID: 22917233)
  20. Zuo S, Jones WK, Li H, He Z, Pasha Z, Yang Y, Wang YG, Fan GC, Ashraf M, Xu M. Paracrine Effect of Wnt11 Overexpressing Mesenchymal Stem Cells on Ischemic Injury.Stem Cells Dev. 2012; 21: 598-608, (PMID: 21463175).
  21. 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. Mesenchymal Stem Cells Overexpressing CXCR4 Attenuate Remodeling of Post-myocardial Infarction by Releasing Matrix Metalloproteinase-9.Stem Cells Dev. 2012; 21:778-89, (PMID: 21671800).
  22. He Z, Li H, Zuo S, Pasha Z, Wang Y, Yang Y, Jiang W, Ashraf M, Xu M. Transduction of Wnt11 Promotes Mesenchymal Stem Cells Transdifferentiation into Cardiac Phenotypes. Stem Cells Dev. 2011,20: 1771-8, (PMID: 21231807).
  23. Dai B, Huang W, Xu M, Millard RW, Gao MH, Hammond HK, Menick DR, Ashraf M, Wang Y. Reduced Collagen Deposition in Infarcted Myocardium Facilitates Induced Pluripotent Stem Cells (iPSC) Engraftment and Angiomyogenesis for Improvement of Left Ventricular Function. J Am CollCardiol,2011; 58:  2118-27 (PMID: 22051336).
  24. Li H, Zuo S, Pasha Z, Yu B, He Z, Wang Y, Yang X, Ashraf M, Xu M.GATA-4 promotes myocardial transdifferentiation of mesenchymal stromal cells via up-regulating IGFBP-4.Cytotherapy. 2011; 13: 1057-1065, (PMID: 21846294).
  25. Li H, Zuo S, He Z, Yang Y, Pasha Z, Wang Y, Xu M.Paracrine Factors Released by GATA-4 Overexpressed Mesenchymal Stem Cells Increase Angiogenesis and Cell Survival.Am J Physiol Heart Circ Physiol. 299(6):H1772-81, 2010.(PMID: 20870802).
  26. Huang W, Zhang D, Millard RW, Wang T, Zhao T, Fan GC, Ashraf A, Xu M, Ashraf M, Wang Y. Gene manipulated peritoneal cell patch repairs infarcted myocardium. J Mol Cell Cardiol.2010; 48:702-12.(PMID: 19913551).
  27. Wang X, Zhao T, Huang W, Wang T, Qian J, Xu M, Kranias EG, Wang Y, Fan GC. Hsp20-Engineered Mesenchymal Stem Cells Are Resistant to Oxidative Stress via Enhanced Activation of Akt and Increased Secretion of Growth Factors.Stem Cells 2009, 27: 3021 – 31.(PMID: 19816949).
  28. Dai Y, Ashraf M, Zuo S, Uemera R, Dai YS, Pasha Z, Haider KhH, Wang Y, Li TY, Xu M.Mobilized bone marrow progenitor cells participate in post-ischemia myocardial repair via secretion of growth factors. J Mol Cell Cardiol. 2008; 44: 607-17. (PMID: 18221754).
  29. Zhang D, Fan GC, Zhou X, Zhao T, Pasha Z, Xu M, Zhu Y, Ashraf M, Wang Y.Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium. J Mol Cell Cardiol.2008; 44: 281-92. (PMID: 18201717).
  30. Dai Y, Xu M*, Pasha Z, Wang Y, Ashraf M. HIF-1α induce VEGF expression by bone marrow stem cell responsible for cardiac protection.J Mol Cell Cardiol. 2007; 42:1036-44. *Corresponding author.(PMID: 17498737).
  31. Xu M, Uemura R, Ying Dai, Yi-Gang Wang, Ashraf M. In vitro and in vivo effects of bone marrow stem cells on cardiac structure and function. J Mol Cell Cardiol. 2007; 42:441-448.(PMID: 17187821).
  32. Uemura R*,Xu M*, Ahmad N, Ashraf M. Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. Circ Res. 2006; 98:1414-21. * contributed equally to this study(PMID: 16690882).
  33. Wang Y, Haider KhH, Ahmad N, Xu M, Ge R, Ashraf M. Combining pharmacological mobilization with intramyocardial delivery of bone marrow cells over-expressing VEGF is more effective for cardiac repair. J Mol Cell Cardiol. 2006; 40:736-45.(PMID: 16603183).
  34. Xu M, Wani M, Dai Y, Wang J, Yan M, Ashraf M. Differentiation of bone marrow stromal cells into cardiac phenotype requires intercellular communication with myocytes. Circulation. 110: 2658-65; 2004. (PMID: 15492307).
  35. Kudo M, Wang Y, Wani MA, Xu M, Ayub A, Ashraf M. Implantation of bone marrow stem cells reduces the infarction and fibrosis in ischemic mouse heart. J Mol Cell Cardiol. 35:1113-9, 2003. (PMID: 12967634).
  36. Xu M,Ashraf M. Melatonin protection against lethal myocyte injury induced by doxorubicin as reflected by effects on mitochondrial membrane potential. J Mol Cell Cardiol 34: 75-79, 2002.  (PMID: 11812166).
  37. Kudo M, Wang YG, Xu M, Ayub A, Ashraf M. Adenosine A1 receptor mediates late preconditioning via activation of PKCd signaling pathway. Am J Physiol Heart CircPhysiol283: H296-H301; 2002.(PMID: 12063302).
  38. Xu M, Wang Y, Ayub A, Ashraf M.Mitochondrial KATP channel activation reduces anoxic injury by restoring mitochondrial membrane potential.  Am J Physiol Heart CircPhysiol 281: H1295-H1303, 2001.(PMID: 11514300).
  39. Xu M, He S, Tang PL, Qian ZM. Melatonin protects against cardiac toxicity.  J Pineal Res. 31: 301-307, 2001. (PMID: 11703558).
  40. Xu M, Wang YG, Hirai K, Ayub A, Ashraf M. Calcium preconditioning inhibits mitochondrial permeability transition and apoptosis. Am J Physiol Heart Circ Physiol. 280: H899-H908, 2001.(PMID: 11158992).
  41. Xu M, Tang PL, Qian ZM, Ashraf M. Effects by doxorubicin on the myocardium are mediated by oxygen free radical. Life Sci. 68: 889-901, 2001. (PMID: 11213359).
  42. Wang Y, Takashi E, Xu M, Ayub A, Ashraf M. Down-regulation of protein kinase C inhibits activation of mitochondrial KATP channels by diazoxide.  Circulation 104: 85-90; 2001. (PMID: 11435343).
  43. Wang Y, kudo M, Xu M, Ayub A, Ashraf M. Mitochondrial KATP channel as an end effector of cardioprotection during late preconditioning: triggering role of nitric oxide. J Mol Cell Cardiol 33: 2037-2046; 2001. (PMID: 11708847).
  44. Tang PL, Xu M, Qian ZM. Differential behavior of cell membranes towards iron-induced oxidative damage and the effects of melatonin. Biol Signals 6:291-300;1997. (PMID: 9500668).
  45. Qian ZM, Xu M, Tang PL. Superoxide dismutase does protect the cultured rat cardiac myocytes against hypoxia/reoxygenation injury. Free Rad Res 27:13-21; 1997. (PMID: 9269575).
  46. Qian ZM, Xu M, Tang PL. Polysaccharide peptide (PSP) restores immune-suppression induced by cyclophosphamide in rats.  Am J Chinese Med XXV (1): 27-35; 1997.(PMID: 9166995).
  47. SZ Liu, Xu M. The protection of anisodamine (654-2) against the acute radiation damage in mouse. ActaAcademiaeMedicinae Suzhou 16 (6): 1054-1055; 1996.
  48. Xu M, Pan JX, Qian ZN, Gu ZL. Antiatherosclerosis effect and mechanism of jianyanling on quail. ActaAcademiaeMedicinae Suzhou 14 (6): 469-472; 1994. 
  49. Xu M,Gu ZL, Qian ZN. The effects of PSP on the immunological function of rats. PSP International Symposium. P.132-136. November, 15-19, 1993.
  50. Xu M, Qian ZN, Gu ZL.  Immune enhancement effect of polysaccharides peptide (PSP) in rats. ActaAcademiae Medicine Suzhou 13 (4): 270-273; 1993.
  51. Xu M, Qian ZN, Gu ZL.  Ligongfang and immune function. Chinese Traditional Patent Medicine 14(11): 43-44; 1992.
  52. Qian ZN, Xu M, Gu ZL. Pharmacological studies on Leaves of ApocynumHendersonii (Hook-F) Woodson. Chinese Traditional Patent Medicine 13 (7): 27-32; 1991.
  53. Xu M, Wang DS, Chan XZ. Effects of superoxide dismutase on ischemia reperfusion injury in isolated working heart and cultured myocardial cells of rats. ActaPharma.Sinica 11: 324-328; 1990. (PMID: 2104486).
  54. Wang DS, Xu M, Chan XZ. Study of pharmacodynamics and adverse reaction of superoxide dismutase. Modern Applied Pharmacy 6(4): 1-6; 1989.

 

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