, Volume 36, Issue 3, pp 738–749

Sca-1-Positive Cardiac Stem Cell migration in a Cardiac Infarction Model



Adult myocardium has the capacity for repair and regeneration, which is derived from cardiac stem cells (CSCs). In this study, we assessed the migration and changes in numbers of Sca-1-positive CSCs after myocardial infarction (MI) in vivo and in vitro. In this study, we showed that in a rat MI model the CSCs emerged around the vessels near the peri-infarct zone and in the epicardium of the infarcted area. Four weeks after infarction, no differences in the expression of connexin 43 (Cx43) were observed in the peri-infarct and infarct zones. In vitro, we mimicked tissue ischemia and hypoxia by using a culture environment of 5 % O2 and a wound healing assay to monitor the migration of CSCs. In conclusion, under hypoxic conditions, the CSCs, conveyed by blood vessels, migrated from the niche to the infarct zone for repairing the damaged myocytes. The number of endogenous migrating CSCs was proportionate to the repair time after infarction, rather than the degree of infarction. Four weeks after MI, the expression of Cx43 was not altered in migratory CSCs, namely no enhanced gap-junctional communication with cardiomyocytes was seen in the CSCs. Further studies are necessary to delineate the molecular mechanisms that drive the migration of CSCs after MI.


cardiac stem cells myocardial infarction migration regeneration hypoxia 



cardiac stem cell


myocardial infarction


acute myocardial infarction


left anterior descending coronary artery


magnetic cell sorting


left ventricle


left ventricular ejection fraction


left ventricular fractional shortening


connexin 43


  1. 1.
    Epstein, J.A., and H. Franklin. 2010. Epstein Lecture. Cardiac development and implications for heart disease. N Engl J Med 363: 1638–1647.PubMedCrossRefGoogle Scholar
  2. 2.
    Hierlihy, A.M., P. Seale, C.G. Lobe, M.A. Rudnicki, and L.A. Megeney. 2002. The post-natal heart contains a myocardial stem cell population. FEBS Lett 530: 239–243.PubMedCrossRefGoogle Scholar
  3. 3.
    Linke, A., Muller, P., Nurzynska, D., Casarsa, C., Torella, D., Nascimbene, A., Castaldo, C., Cascapera, S., Bohm, M., Quaini, F., and other 5 authors. 2005. Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. Proceedings of the National Academy of Sciences of the United States of America 102: 8966–8971.Google Scholar
  4. 4.
    Matsuura, K., T. Nagai, N. Nishigaki, T. Oyama, J. Nishi, H. Wada, M. Sano, H. Toko, H. Akazawa, and T. Sato. 2004. Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. Journal of Biological Chemistry 279: 11384–11391.PubMedCrossRefGoogle Scholar
  5. 5.
    Beltrami, A.P., Barlucchi, L., Torella, D., Baker, M., Limana, F., Chimenti, S., Kasahara, H., Rota, M., Musso, E., Urbanek, K., and other 4 authors. 2003. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114: 763–776.Google Scholar
  6. 6.
    Torella, D., C. Indolfi, D.F. Goldspink, and G.M. Ellison. 2008. Cardiac stem cell-based myocardial regeneration: towards a translational approach. Cardiovasc Hematol Agents Med Chem 6: 53–59.PubMedCrossRefGoogle Scholar
  7. 7.
    Messina, E., L. De Angelis, G. Frati, S. Morrone, S. Chimenti, F. Fiordaliso, M. Salio, M. Battaglia, M.V.G. Latronico, and M. Coletta. 2004. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circulation research 95: 911–921.PubMedCrossRefGoogle Scholar
  8. 8.
    Rossini, A., A. Zacheo, D. Mocini, P. Totta, A. Facchiano, R. Castoldi, P. Sordini, G. Pompilio, D. Abeni, M.C. Capogrossi, and A. Germani. 2008. HMGB1-stimulated human primary cardiac fibroblasts exert a paracrine action on human and murine cardiac stem cells. J Mol Cell Cardiol 44: 683–693.PubMedCrossRefGoogle Scholar
  9. 9.
    Rossini, A., C. Frati, C. Lagrasta, G. Graiani, A. Scopece, S. Cavalli, E. Musso, M. Baccarin, M. Di Segni, and F. Fagnoni. 2011. Human cardiac and bone marrow stromal cells exhibit distinctive properties related to their origin. Cardiovascular research 89: 650–660.PubMedCrossRefGoogle Scholar
  10. 10.
    Dawn, B., A.B. Stein, K. Urbanek, M. Rota, B. Whang, R. Rastaldo, D. Torella, X.L. Tang, A. Rezazadeh, and J. Kajstura. 2005. Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. Proceedings of the National Academy of Sciences of the United States of America 102: 3766.PubMedCrossRefGoogle Scholar
  11. 11.
    Torella, D., G.M. Ellison, S. Méndez-Ferrer, B. Ibanez, and B. Nadal-Ginard. 2006. Resident human cardiac stem cells: Role in cardiac cellular homeostasis and potential for myocardial regeneration. Nature Clinical Practice Cardiovascular Medicine 3: S8–S13.PubMedCrossRefGoogle Scholar
  12. 12.
    Kuang, D., X. Zhao, G. Xiao, J. Ni, Y. Feng, R. Wu, and G. Wang. 2008. Stem cell factor/c-kit signaling mediated cardiac stem cell migration via activation of p38 MAPK. Basic research in cardiology 103: 265–273.PubMedCrossRefGoogle Scholar
  13. 13.
    Hochman, J.S., and B.H. Bulkley. 1982. Expansion of acute myocardial infarction: an experimental study. Circulation 65: 1446–1450.PubMedCrossRefGoogle Scholar
  14. 14.
    Bearzi, C., M. Rota, T. Hosoda, J. Tillmanns, A. Nascimbene, A. De Angelis, S. Yasuzawa-Amano, I. Trofimova, R.W. Siggins, and N. LeCapitaine. 2007. Human cardiac stem cells. Proceedings of the National Academy of Sciences 104: 14068.CrossRefGoogle Scholar
  15. 15.
    Urbanek, K., D. Torella, F. Sheikh, A. De Angelis, D. Nurzynska, F. Silvestri, C.A. Beltrami, R. Bussani, A.P. Beltrami, and F. Quaini. 2005. Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proceedings of the National Academy of Sciences of the United States of America 102: 8692.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Jingjin Liu
    • 1
    • 2
  • Yongshun Wang
    • 1
    • 2
  • Wenjuan Du
    • 1
    • 2
  • Bo Yu
    • 1
    • 2
  1. 1.Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and TreatmentHarbinChina
  2. 2.Depatment of CardiologySecond Affiliated Hospital of Harbin Medical UniversityHarbinChina

Personalised recommendations