Buckled structures and 5-azacytidine enhance cardiogenic differentiation of adipose-derived stem cells

Myocardial infarction is caused after impairment of heart wall muscle following an immense cell loss and also when the myocardial tissue is lacking the inherent capacity to regenerate for normal functioning of myocardium. An immediate challenge in cardiac regeneration is to devise a strategy that leads to a reproducible degree of cardiac differentiation. We have speculated that ex vivo pretreatment of adipose-derived stem cells (ADSCs) using 5-azacytidine and a suitable patterned nanofibrous construct could lead to cardiomyogenic differentiation and results in superior biological and functional effects on cardiac regeneration of infarcted myocardium.

Polyglycerol sebacate/gelatin fibers were fabricated by core/shell electrospinning with polyglycerol sebacate as the core material and gelatin as the shell material. Patterning of the core/shell fibers to form orthogonal and looped buckled nanostructures was achieved.

Results demonstrated that the buckled fibers showing an orthogonal orientation and looped pattern had a Young's modulus of approximately 3.59 ± 1.58 MPa and 2.07 ± 0.44 MPa, respectively, which was comparable to that of native myocardium. The ADSCs cultured on these scaffolds demonstrated greater expression of the cardiac-specific marker proteins actinin, troponin and connexin 43, as well as characteristic multinucleation as shown by immunocytochemical and morphological analysis, indicating complete cardiogenic differentiation of ADSCs.

In the natural milieu, cardiomyogenic differentiation probably involves multiple signaling pathways and we have postulated that a buckled structure combination of chemical treatment and environment-driven strategy induces cardiogenic differentiation of ADSCs. The combination of patterned buckled fibrous structures with stem cell biology may prove to be a productive device for myocardial infarction.