Mesenchymal stem cells overexpressing integrin-linked kinase attenuate cardiac fibroblast proliferation and collagen synthesis through paracrine actions

Mesenchymal stem cells (MSCs) transfected by integrin-linked kinase (ILK) transplantation may improve the function and compliance of the post-infarct cardiac ventricle. We investigated the effect of ILK-modified MSC contiditioned medium (ILK-MSC-CM) on the proliferation of cardiac fibroblasts (CFBs) and collagen synthesis in vitro and in vivo. Myocardial infarction (MI)-induced animals received mesenchymal stem cell conditioned medium (MSC-CM), ILK-MSC-CM, or complete medium alone, subepicardially. A group of animals with MI and no other former intervention served as controls. ILK-MSC-CM inhibited CFB proliferation, reduced the gene expression of type I (Collal) and type III collagen (Col3a1), tissue inhibitors of metalloproteinase-1 (TIMP-1) and -2 (TIMP-2), alpha smooth muscle actin (alpha-SMA), and connective tissue growth factor (CTGF). It also increased the gene expression of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9), as measured by qRT-PCR. Four weeks after the left anterior descending (LAD) coronary artery ligation, echocardiographic analysis demonstrated preserved cardiac geometry and contractility in the ILK-MSC-CM treated animals. Decreased infarct size and reduced fibrosis were observed in the ILK-MSC-CM group. Overexpression of ILK regulates paracrine actions of MSCs, and ILK-MSC-CM attenuates CFB proliferation and collagen synthesis through paracrine actions in vitro and in vivo.