A G-CSF functionalized scaffold for stem cells seeding: A differentiating device for cardiac purposes

Cristiano Spadaccio, Alberto Rainer, Marcella Trombetta, Matteo Centola, Mario Lusini, Massimo Chello, Elvio Covino, Federico De Marco, Raffaella Coccia, Yoshiya Toyoda, Jorge A. Genovese

Research output: Contribution to journalArticle

Abstract

Myocardial infarction and its consequences represent one of the most demanding challenges in cell therapy and regenerative medicine. Transfer of skeletal myoblasts into decompensated hearts has been performed through intramyocardial injection. However, the achievements of both cardiomyocyte differentiation and precise integration of the injected cells into the myocardial wall, in order to augment synchronized contractility and avoid potentially life-threatening alterations in the electrical conduction of the heart, still remain a major target to be pursued. Recently, granulocytes colony-stimulating factor (G-CSF) fuelled the interest of researchers for its direct effect on cardiomyocytes, inhibiting both apoptosis and remodelling in the failing heart and protecting from ventricular arrhythmias through the up-regulation of connexin 43 (Cx43). We propose a tissue engineering approach concerning the fabrication of an electrospun cardiac graft functionalized with G-CSF, in order to provide the correct signalling sequence to orientate myoblast differentiation and exert important systemic and local effects, positively modulating the infarction microenvironment. Poly-(l-lactide) electrospun scaffolds were seeded with C2C12 murine skeletal myoblast for 48 hrs. Biological assays demonstrated the induction of Cx43 expression along with morphostructural changes resulting in cell elongation and appearance of cellular junctions resembling the usual cardiomyocyte arrangement at the ultrastructural level. The possibility of fabricating extracellular matrix-mimicking scaffolds able to promote myoblast pre-commitment towards myocardiocyte lineage and mitigate the hazardous environment of the damaged myocardium represents an interesting strategy in cardiac tissue engineering.

Original languageEnglish
Pages (from-to)1096-1108
Number of pages13
JournalJournal of Cellular and Molecular Medicine
Volume15
Issue number5
DOIs
Publication statusPublished - May 2011

Keywords

  • 3D scaffold
  • Cardiac graft
  • Connexin 43
  • Differentiation
  • Electrospinning
  • G-CSF release
  • PLLA
  • Stem cells
  • Tissue engineering

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

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  • Cite this

    Spadaccio, C., Rainer, A., Trombetta, M., Centola, M., Lusini, M., Chello, M., Covino, E., De Marco, F., Coccia, R., Toyoda, Y., & Genovese, J. A. (2011). A G-CSF functionalized scaffold for stem cells seeding: A differentiating device for cardiac purposes. Journal of Cellular and Molecular Medicine, 15(5), 1096-1108. https://doi.org/10.1111/j.1582-4934.2010.01100.x