Skip to main content

Cardiac Stem Cells Derived from Epithelial-Mesenchymal Transition of the Epicardial Cells: Role in Heart Regeneration (Method)

  • Chapter
  • First Online:
Book cover Stem Cells and Cancer Stem Cells, Volume 5

Part of the book series: Stem Cells and Cancer Stem Cells ((STEM,volume 5))

  • 1128 Accesses

Abstract

Epithelial-mesenchymal transition (EMT) involves genotypic and phenotypic changes leading to the conversion of polarized epithelial cells into motile mesenchymal cells. This process occurs typically in mesothelial cells of developing cardiac tissue, but recent discoveries indicate the preservation or reactivation of embryonic potential of epicardial cells in the adult heart. Moreover, cells with cardiac stem cell phenotype and properties have been identified among epicardially derived cell (EPDC) population, indicating EMT and EPDCs as yet another source of cells for adult cardiac tissue regeneration in cardiovascular diseases. Understanding how and when EPDCs arise from epicardial cells by EMT in the adult human heart could have a strong impact in clarifying the mechanisms of cardiac tissue self-renewal and regeneration. The chapter includes a protocol for adult human epicardial cell culture and EMT induction leading to a formation of cardiac progenitor cells in vitro.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Baum B, Settleman J, Quinlan MP (2008) Transitions between epithelial and mesenchymal states in development and disease. Semin Cell Dev Biol 19:294–308

    Article  PubMed  CAS  Google Scholar 

  • Bearzi C, Rota M, Hosoda T, Tillmanns J, Nascimbene A, De Angelis A, Yasuzawa-Amano S, Trofimova I, Siggins RW, Lecapitaine N, Cascapera S, Beltrami AP, D’Alessandro DA, Zias E, Quaini F, Urbanek K, Michler RE, Bolli R, Kajstura J, Leri A, Anversa P (2007) Human cardiac stem cells. Proc Natl Acad Sci USA 104:14068–14073

    Article  PubMed  CAS  Google Scholar 

  • Castaldo C, Di Meglio F, Nurzynska D, Romano G, Maiello C, Bancone C, Müller P, Böhm M, Cotrufo M, Montagnani S (2008) CD117-positive cells in adult human heart are localized in the subepicardium, and their activation is associated with laminin-1 and alpha6 integrin expression. Stem Cells 26:1723–1731

    Article  PubMed  CAS  Google Scholar 

  • Dettman RW, Denetclaw W Jr, Ordahl CP, Bristow J (1998) Common epicardial origin of coronary vascular smooth muscle, perivascular fibroblasts, and intermyocardial fibroblasts in the avian heart. Dev Biol 193:169–181

    Article  PubMed  CAS  Google Scholar 

  • Di Meglio F, Castaldo C, Nurzynska D, Romano V, Miraglia R, Bancone C, Langella G, Vosa C, Montagnani S (2010a) Epithelial-mesenchymal transition of epicardial mesothelium is a source of cardiac CD117-positive stem cells in adult human heart. J Mol Cell Cardiol 49:719–727

    Article  PubMed  Google Scholar 

  • Di Meglio F, Castaldo C, Nurzynska D, Romano V, Miraglia R, Montagnani S (2010b) Epicardial cells are missing from the surface of hearts with ischemic cardiomyopathy: a useful clue about the self-renewal potential of the adult human heart? Int J Cardiol 145:e44–e46

    Article  PubMed  Google Scholar 

  • Eid H, Larson DM, Springhorn JP, Attawia MA, Nayak RC, Smith TW, Kelly RA (1992) Role of epicardial mesothelial cells in the modification of phenotype and function of adult rat ventricular myocytes in primary coculture. Circ Res 71:40–50

    PubMed  CAS  Google Scholar 

  • Eralp I, Lie-Venema H, Bax NA, Wijffels MC, Van Der Laarse A, Deruiter MC, Bogers AJ, Van Den Akker NM, Gourdie RG, Schalij MJ, Poelmann RE, Gittenberger-De Groot AC (2006) Epicardium-derived cells are important for correct development of the Purkinje fibers in the avian heart. Anat Rec A Discov Mol Cell Evol Biol 288:1272–1280

    PubMed  Google Scholar 

  • Freshney RI (2000) Culture of animal cells: a manual of basic techniques, 4th edn. Wiley-Liss, New York, pp 159–175

    Google Scholar 

  • Gambini E, Pompilio G, Biondi A, Alamanni F, Capogrossi MC, Agrifoglio M, Pesce M (2010) C-kit+  cardiac progenitors exhibit mesenchymal markers and preferential cardiovascular commitment. Cardiovasc Res 89:362–373

    Article  PubMed  Google Scholar 

  • Gittenberger-de Groot AC, Vrancken Peeters MP, Mentink MM, Gourdie RG, Poelmann RE (1998) Epicardium-derived cells contribute a novel population to the myocardial wall and the atrioventricular cushions. Circ Res 82:1043–1052

    PubMed  CAS  Google Scholar 

  • Hay ED (2005) The mesenchymal cell, its role in the embryo, and the remarkable signalling mechanisms that create it. Dev Dyn 233:706–720

    Article  PubMed  CAS  Google Scholar 

  • Laflamme MA, Murry CE (2011) Heart regeneration. Nature 473:326–335

    Article  PubMed  CAS  Google Scholar 

  • Limana F, Bertolami C, Mangoni A, Di Carlo A, Avitabile D, Mocini D, Iannelli P, De Mori R, Marchetti C, Bozzoli O, Gentili C, Zacheo A, Germani A, Capogrossi MC (2010) Myocardial infarction induces embryonic reprogramming of epicardial c-kit(+) cells: role of the pericardial fluid. J Mol Cell Cardiol 48:609–618

    Article  PubMed  CAS  Google Scholar 

  • Martínez-Estrada OM, Lettice LA, Essai A, Guadix JA, Slight J, Velacela V, Hall E, Reichmann J, Devenney PS, Hohenstein P, Hosen N, Hill RE, Muñoz-Chapuli R, Hastie ND (2010) Wt1 is required for cardiovascular progenitor cell formation through transcriptional control of Snail and E-cadherin. Nat Genet 42:89–93

    Article  PubMed  Google Scholar 

  • Mirotsou M, Jayawardena TM, Schmeckpeper J, Gnecchi M, Dzau VJ (2011) Paracrine mechanisms of stem cell reparative and regenerative actions in the heart. J Mol Cell Cardiol 50:280–289

    Article  PubMed  CAS  Google Scholar 

  • Rangappa S, Makkar R, Forrester J (2010) Current status of myocardial regeneration: new cell sources and new strategies. J Cardiovasc Pharmacol Ther 15:338–343

    Article  PubMed  Google Scholar 

  • Shah AP, Youngquist ST, McClung CD, Tzvetkova E, Hanif MA, Rosborough JP, Niemann JT (2011) Markers of progenitor cell recruitment and differentiation rise early during ischemia and continue during resuscitation in a porcine acute ischemia model. J Interferon Cytokine Res 31:509–513

    Article  PubMed  CAS  Google Scholar 

  • Smart N, Risebro CA, Melville AA, Moses K, Schwartz RJ, Chien KR, Riley PR (2007) Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization. Nature 445:177–1782

    Article  PubMed  CAS  Google Scholar 

  • Smart N, Risebro CA, Clark JE, Ehler E, Miquerol L, Rossdeutsch A, Marber MS, Riley PR (2010) Thymosin beta4 facilitates epicardial neovascularization of the injured adult heart. Ann N Y Acad Sci 1194:97–104

    Article  PubMed  CAS  Google Scholar 

  • Smart N, Bollini S, Dubé KN, Vieira JM, Zhou B, Davidson S, Yellow D, Riegler J, Price AN, Lythgoe MF, Pu WT, Riley PR (2011) De novo cardiomyocytes from within the activated adult heart after injury. Nature. doi:10.1038/nature10188

  • Stevens MV, Broka DM, Parker P, Rogowitz E, Vaillancourt RR, Camenisch TD (2008) MEKK3 initiates transforming growth factor beta 2-dependent epithelial-to-mesenchymal transition during endocardial cushion morphogenesis. Circ Res 103:1430–1440

    Article  PubMed  CAS  Google Scholar 

  • Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2:442–454

    Article  PubMed  CAS  Google Scholar 

  • Thiery JP, Sleeman JP (2006) Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 7:131–142

    Article  PubMed  CAS  Google Scholar 

  • van Wijk B, van den Berg G, Abu-Issa R, Barnett P, van der Velden S, Schmidt M, Ruijter JM, Kirby ML, Moorman AF, van den Hoff MJ (2009) Epicardium and myocardium separate from a common precursor pool by crosstalk between bone morphogenetic protein- and fibroblast growth factor-signaling pathways. Circ Res 105:431–441

    Article  PubMed  Google Scholar 

  • VanWinkle WB, Snuggs MB, Buja LM (1996) Cardiogel: a biosynthetic extracellular matrix for cardiomyocyte culture. In Vitro Cell Dev Biol Anim 32:478–485

    Article  PubMed  CAS  Google Scholar 

  • Weeke-Klimp A, Bax NA, Bellu AR, Winter EM, Vrolijk J, Plantinga J, Maas S, Brinker M, Mahtab EA, Gittenberger-de Groot AC, van Luyn MJ, Harmsen MC, Lie-Venema H (2010) Epicardium-derived cells enhance proliferation, cellular maturation and alignment of cardiomyocytes. J Mol Cell Cardiol 49:606–616

    Article  PubMed  CAS  Google Scholar 

  • Wessels A, Pérez-Pomares JM (2004) The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells. Anat Rec A Discov Mol Cell Evol Biol 276:43–57

    Article  PubMed  CAS  Google Scholar 

  • Winter EM, Grauss RW, Hogers B, van Tuyn J, van der Geest R, Lie-Venema H, Steijn RV, Maas S, DeRuiter MC, de Vries AA, Steendijk P, Doevendans PA, van der Laarse A, Poelmann RE, Schalij MJ, Atsma DE, Gittenberger-de Groot AC (2007) Preservation of left ventricular function and attenuation of remodeling after transplantation of human epicardium-derived cells into the infarcted mouse heart. Circulation 116:917–927

    Article  PubMed  CAS  Google Scholar 

  • Zeisberg M, Neilson EG (2009) Biomarkers for ­epithelial-mesenchymal transitions. J Clin Invest 119:1429–1437

    Article  PubMed  CAS  Google Scholar 

  • Zhou B, Ma Q, Rajagopal S, Wu SM, Domian I, Rivera-Feliciano J, Jiang D, von Gise A, Ikeda S, Chien KR, Pu WT (2008) Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature 454:109–113

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Daria Nurzynska .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Nurzynska, D., Di Meglio, F., Montagnani, S., Castaldo, C. (2012). Cardiac Stem Cells Derived from Epithelial-Mesenchymal Transition of the Epicardial Cells: Role in Heart Regeneration (Method). In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 5. Stem Cells and Cancer Stem Cells, vol 5. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2900-1_11

Download citation

Publish with us

Policies and ethics