Angiogenesis and myogenesis using human skeletal myoblasts for cardiac repair

Abstract

Human skeletal myoblasts carrying hVEGF165 or Ang-1, or simultaneous hVEGF165 and Ang-1 efficiently expressed angiogenic factors. The genetically modulated human skeletal myoblasts labeled with Lac-z reporter gene, were transplanted in rodent and porcine heart model of myocardial infarction using transient immunosuppression. Histochemical studies for Lac-z expression showed that myoblasts successfully survived post transplantation. Transduced human skeletal myoblasts helped to significantly improve the global heart function in the porcine heart model. Histological studies and PCR revealed transient expression of the transferred angiogenic genes with significantly increased neovascularization and improved regional blood flow. An interesting feature of the study was the formation of heterokaryons between the donor myoblasts and the host cardiomyocytes which suggested a fusion between the two populations of cells. We conclude that the combo-therapy of combining myoblast transplantation with angiogenesis is feasible, safe, and more efficient for treatment of myocardial infarction.