The effect of mesenchymal stem cell (MSCs)-based therapy on treating acute myocardial infarction (MI) is limited due to poor engraftment and limited regenerative potential. Here we engineered MSCs with integrin-linked kinase (ILK)， a pleiotropic protein critically regulating cell survival， proliferation， differentiation， and angiogenesis. We firstly combined ferumoxytol with poly-L-lysine (PLL)， and found this combination promisingly enabled MRI visualization of MSCs in vitro and in vivo with good safety. We provided visually direct evidence that intracoronary ILK-MSCs had substantially enhanced homing capacity to infarct myocardium in porcine following cardiac catheterization induced MI. Intracoronar... More
The effect of mesenchymal stem cell (MSCs)-based therapy on treating acute myocardial infarction (MI) is limited due to poor engraftment and limited regenerative potential. Here we engineered MSCs with integrin-linked kinase (ILK)， a pleiotropic protein critically regulating cell survival， proliferation， differentiation， and angiogenesis. We firstly combined ferumoxytol with poly-L-lysine (PLL)， and found this combination promisingly enabled MRI visualization of MSCs in vitro and in vivo with good safety. We provided visually direct evidence that intracoronary ILK-MSCs had substantially enhanced homing capacity to infarct myocardium in porcine following cardiac catheterization induced MI. Intracoronary transplantation of allogeneic ILK-MSCs， but not vector-MSCs， significantly enhanced global left ventricular ejection fraction (LVEF) by 7.8% compared with baseline， by 10.3% compared with vehicles， and inhibited myocardial remodeling compared with vehicles at 15-day follow-up. Compared with vector-MSCs， ILK-MSCs significantly improved regional LV contractile function， reduced scar size， fibrosis， cell apoptosis， and increased regional myocardial perfusion and cell proliferation. This preclinical study indicates that ILK-engineered MSCs might promote the clinical translation of MSC-based therapy in post-MI patients， and provides evidence that ferumoxytol labeling of cells combined with PLL is feasible in in vivo cell tracking.
