Choice of cell-delivery route for successful cell transplantation therapy for the heart

The cell-delivery route is one of the major factors influencing the therapeutic effect and complications of cell transplantation therapy for cardiac diseases. There are four major clinically practical routes, with each method having its own advantages and disadvantages. First, intramyocardial injection allows targeted cell delivery into the areas of interest, although this induces mechanical injury, inflammation and islet-like donor cell clusters, leading to limited donor cell survival and arrhythmogenicity. Second, intracoronary injection is less likely to induce inflammation, whereas poor initial cell retention in the heart is a concern. Third, intravenous injection is easy and economical, but cell recruitment into the heart is not frequent. Finally, epicardial placement of 'cell sheets' enables higher efficiency of cell engraftment, but poor integration into the myocardium may be an issue. This review summarizes up-to-date clinical and preclinical knowledge regarding these cell-delivery methods. We further discuss the ways to refine these methods towards optimizing cell transplantation therapy for the heart.