Transplantation of MSCs transfected with SHH gene ameliorates cardiac dysfunction after chronic myocardial infarction

摘要

Recently, it has been discovered that Sonic hedgehog (SHH) is important for the maintenance and repair of the adult cardiovascular system [1,2]. Thus, the SHH gene could be a possible candidate gene for gene therapy to ischemic heart disease. Kusano et al. injected naked DNA encoding the SHH gene into a myocardial infarction (MI) area and found that SHH gene transfer improved left ventricular function after MI [3]. At this stage, we have tried to transfer the SHH gene into mesenchymal stem cells (MSCs) and found that transplantation of MSCs transfected with SHH gene can ameliorate cardiac dysfunction after chronic MI.Firstly, we transferred the SHH gene into MSCs successfully. As the SHH precursor protein has the ability to autocatalyze, it can hence mature in cells [4]. Therefore the SHH-N segment was not selected as before, but instead the complete code sequence of SHH was used in our study. The Nucleofector? was used to transfer pmaxGFP into MSCs. The expression of green fluorescence was observed 24 h following transfec-tion, which confirmed that the transfection efficiency was 30%-40%. 48 h following pcDNA3.1-SHH transfection, reverse transcription-PCR, Western blot analysis and real-time PCR demonstrated that the expression of SHH mRNA had significantly increased in transfected MSCs in comparison to untransfected MSCs.