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

Abstract

One of the major obstacles in the creation of 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 mice. Female mice were randomly placed into the following three groups: 1) fibroblasts transfected with β-galactosidase-containing adenovirus (control group), 2) fibroblasts treated with a necrosis inhibitor (NI group), and 3) fibroblasts transfected with Akt-containing adenovirus (Akt group). Pretreated cells were transplanted into the recipient heart by direct injection after a 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 group) and 7 (Akt group) times greater at 21 days compared with the control group. Increased fibrosis and conduction delay were also observed in the NI and Akt groups compared with the control group. 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 a novel strategy to treat arrhythmias.