One of the major obstacles to create myocardial fibrosis using fibroblasts is massive cell death after cell injection. To overcome this problem, a method that delivers fibroblasts primed with survival factors was studied. Cardiac fibroblasts were isolated from wild-type male C57BL/6. Female mice were randomly placed into the following three groups: (1) fibroblasts transfected with beta-galactosidase adenovirus (control group); (2) fibroblasts treated with a necrosis inhibitor (NI group); and (3) fibroblasts transfected with Akt-adenovirus (Akt group). The pretreated cells were transplanted into the recipient heart by direct injection following thoracotomy. Quantitative real-time PCR and morphometric analysis were performed to investigate the effects of survival-factor priming on the induction of cell engraftment and fibrosis. In addition, a canine model was used to investigate the development of fibrosis and conduction modification using autologous dermal fibroblasts. The NI and Akt groups showed a better engraftment rate: 13 (NI) and 7 (Akt) times greater at 21 days compared to the control group. Increased fibrosis and conduction delay were also observed in the NI and Akt groups compared to the controls. Survival-factor priming increased cellular engraftment and enhanced the efficacy of cell transplantation. Delivery of fibroblasts primed with survival factors might be a promising approach to develop conduction modification as novel strategy to treat arrhythmias.