Creation of myocardial fibrosis by transplantation of fibroblasts primed with survival factors.

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.