A G-CSF functionalized scaffold for stem cells seeding: a differentiating device for cardiac purposes.
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.
Spadaccio
Cristiano
C
CIR - Area of Cardiovascular Surgery, University Campus Bio-Medico of Rome, Rome, Italy.
Rainer
Alberto
A
Trombetta
Marcella
M
Centola
Matteo
M
Lusini
Mario
M
Chello
Massimo
M
Covino
Elvio
E
De Marco
Federico
F
Coccia
Raffaella
R
Toyoda
Yoshiya
Y
Genovese
Jorge A
JA
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D018031:Connexin 43 / Q000096:biosynthesis / Q000235:genetics; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism / Q000627:therapeutic use*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D009203:Myocardial Infarction / Q000628:therapy; D011091:Polyesters / Q000627:therapeutic use; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D023822:Tissue Engineering; D054457:Tissue Scaffolds
D018031:Connexin 43; D011091:Polyesters; D016179:Granulocyte Colony-Stimulating Factor; C033616:poly(lactide)