Enhancement of adipose-derived stem cell differentiation in scaffolds with IGF-I gene impregnation under dynamic microenvironment.
Zhu Y., Liu T., Ye H., Song K., Ma X., Cui Z.
Biochemical and mechanical signals enabling cardiac regeneration can be elucidated by using in vitro tissue engineering models. We hypothesized that human insulin-like growth factor-I (IGF-I) and 3-dimensional (3D) dynamic microenvironment could enhance the survival and differentiation of adipose tissue-derived stem cells (ADSCs). In this study, ADSCs were cultured on 3D porous scaffolds with or without plasmid DNA PIRES2-IGF-I in cardiac media, in static culture dishes, and in a spinning flask bioreactor, respectively. Cell viability, formation of cardiac-like structure, expression of functional proteins, and gene expressions were tested in the cultured constructs on day 14. The results showed that dynamic microenvironment enhanced the release of plasmid DNA; the ADSCs can be transfected by the released plasmid DNA PIRES2-IGF-I in scaffold. IGF-I showed beneficial effects on cellular viability and increase of total protein and also increased the expressions of cardiac-specific proteins and genes in the grafts. It was also demonstrated that dynamic stirring environment could promote the proliferation of ADSCs. Therefore, IGF-I, expressed by ADSCs transfected by DNA PIRES2-IGF-I incorporated into scaffold, and hydrodynamic microenvironment can independently and interactively increase cellular viability and interactively increase the expression of cardiac-specific proteins and genes in the grafts. The results would be useful for developing tissue-engineered grafts for myocardial repair.