POLYCISTRONIC HSV VECTORS FOR THE DIFFERENTIATION OF EMBRYONIC STEM CELLS TOWARD A CARDIAC LINEAGE

摘要: Cardiovascular disease is the leading cause of death in developed countries, but we lack ability to regenerate cardiac tissue. Cell-based therapy holds promise repopulate a damaged heart with functional cardiomyocytes. Developing technologies produce cells for transplantation key success this approach. Pluripotent stem (PSC) are an ideal starting material cell-based therapies because they can be expanded indefinitely culture and their plasticity gives them potential any tissue or organ. The issue teratoma formation host may avoided by devising methods differentiate PSC toward desired lineage before transplantation. Because vital life, biggest source human morbidity mortality, vitro differentiation into cardiomyocytes treatment area intense research. Exogenous expression cardiogenic genes powerful tool. Transduction recombinant viral vectors deliver activate programming drive lineage. Replication defective HSV efficiently transduce engineered express that alter cellular program. goal research was develop highly multiple transcription factors embryonic increase potential. Vectors vββG4Nk, vG4Nk, vGTM were GATA4 NKX2.5 GATA4, TBX5, MEF2c high efficiency low toxicity. mESC these induced endogenous cardiogenesis. Differentiation transduced had positive impact on terminal cardiomyocyte differentiation, producing many more embryoid bodies beating than those control vectors. In addition, found delaying drastic dilution genomes occurs over time interval could enhance outcome. Our results indicate infection has long reaching effects supporting suggestion useful tool related changes differentiating generate specialized cell types.