Invited Commentary

Abstract

In recent years, stem cell therapy has received considerable attention as a novel therapeutic option for refractory congestive heart failure. Although the mechanisms through which these cells elicit functional improvement are yet to be fully determined, recent studies suggest that paracrine effects, rather than direct trans-differentiation of donor cells into cardiomyocytes, may predominate in augmenting postinfarction cardiac function. Progress in cell therapy, however, is hampered by suboptimal engraftment of donor cells into the myocardium, related to the extensive cell death that ensues from the hostile milieu into which the donor cells are introduced. This problem has stimulated further investigation of the use of bioengineered scaffolds as cell delivery vehicles, with the hope that these constructs may enhance cell retention and functional recovery. In this study, Hamdi and colleagues [1Hamdi H. Furuta A. Bellamy V. et al.Cell delivery: intramyocardial injections or epicardial deposition? A head-to-head comparison.Ann Thorac Surg. 2009; 87: 1196-1204Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar] evaluated the effect of differing cell delivery techniques on postinfarct heart function. Using skeletal myoblasts as donor cells in a rat infarct model, the authors compared the conventional intramyocardial injection technique with epicardial placement of two cell-seeded constructs, one made of a double-layered myoblast cell sheet and the other constructed from a cell-seeded Gelfoam (Pharmacia & Upjohn/Pfizer, New York, NY) patch. The authors concluded that the two epicardially delivered tissue scaffolds led to significant improvements in left ventricular ejection fraction (LVEF) compared with the controls injected with culture medium, whereas intramyocardial injection prevented further deterioration of ventricular function but did not improve LVEF. Histologic analysis also showed greater angiogenesis in the two epicardially treated groups. The major quandary posed by these findings is that the effects of the varying techniques of cell transfer were unrelated to the detectable persistence of the myoblasts at the studied time point. Analysis of cell engraftment revealed minimal donor cell retention, with residual human cells detected in only 2 of 7 hearts in each of the two groups treated with the epicardial scaffold. The authors attribute the between-group differences in LVEF to donor cell effects at earlier, unevaluated time points (ie, earlier than 1 month). Their analysis of cytokines 1 month after cell delivery showed no differences between groups that might explain differences in functional recovery, but this, like the absence of persistent donor cells, may merely be a reflection of the time point chosen. Somewhat surprisingly, end-systolic and end-diastolic volumes did not differ between groups. Thus, although the cell sheets and Gelfoam patch improved LVEF, they did not do so by reducing infarct expansion compared with intramyocardial injection. Ultimately, the lack of a demonstrable mechanism to explain the differences observed between groups somewhat limits the strength of the conclusions that can be drawn about the relative merits of these different cell delivery techniques. Regardless, this is a topical study that compares the conventional intramyocardial delivery method to two potentially attractive methods of epicardial delivery. The results are provocative, and should spur further investigation to determine whether there are intrinsic benefits in using biomaterials in the setting of a recent or remote myocardial infarction. If there are, what are the mechanisms through which these constructs exert synergistic effects with the seeded cells? The optimal cell type or mixture of cell types that is best suited to a particular scaffold material has not been determined, nor have the physical, electrical, or surface characteristics that render one cell type more appropriate for seeding than another. Those studies may eventually lead to the development of off-the-shelf bioengineered cell-seeded constructs that may sidestep the issues of cell harvesting, expansion, and delivery that complicate current applications of cell therapy. Cell Delivery: Intramyocardial Injections or Epicardial Deposition? A Head-to-Head ComparisonThe Annals of Thoracic SurgeryVol. 87Issue 4PreviewMultiple needle-based injections of cells in the myocardium are associated with a low engraftment rate, which may limit the benefits of the procedure. This study used skeletal myoblasts to perform a head-to-head comparison of conventional injections with epicardial deposition of scaffold-embedded cells. Full-Text PDF