Abstract
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.
Similar content being viewed by others
Change history
12 August 2020
After publication of our article [1], we became aware that there were errors in Fig. 1, namely that the Echocardiographic assessment of 1w, 2w, and 4w groups was incorrectly presented.
Abbreviations
- CSC:
-
cardiac stem cell
- MI:
-
myocardial infarction
- AMI:
-
acute myocardial infarction
- LAD:
-
left anterior descending coronary artery
- MACS:
-
magnetic cell sorting
- LV:
-
left ventricle
- LVEF:
-
left ventricular ejection fraction
- LVFS:
-
left ventricular fractional shortening
- Cx43:
-
connexin 43
References
Epstein, J.A., and H. Franklin. 2010. Epstein Lecture. Cardiac development and implications for heart disease. N Engl J Med 363: 1638–1647.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Hochman, J.S., and B.H. Bulkley. 1982. Expansion of acute myocardial infarction: an experimental study. Circulation 65: 1446–1450.
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.
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.
Acknowledgments
This study was supported in part by a grant from the National Natural Science Foundation of China (to B.Y., Grant No. 30871064). The authors thank Baixiang Li, Wei Liu and Hulun Li for their helps with technical assistance, and also thank Dr. Meng Sun for assistance with the statistics.
Author information
Authors and Affiliations
Corresponding author
Additional information
J. Liu and Y. Wang contributed equally to this work.
Rights and permissions
About this article
Cite this article
Liu, J., Wang, Y., Du, W. et al. Sca-1-Positive Cardiac Stem Cell migration in a Cardiac Infarction Model. Inflammation 36, 738–749 (2013). https://doi.org/10.1007/s10753-013-9600-8
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10753-013-9600-8