The End of Granulocyte Colony-Stimulating Factor in Acute Myocardial Infarction?

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“Perfect as the wing of a bird may be, it will never enable the bird to fly if unsupported by the air. Facts are the air of science. Without them a man of science can never rise.” — —Ivan Pavlov Facts must be sought from the rigorous application of scientific method. Indeed, the hardest questions sometimes require the hardest methods. Having a tool that can answer the questions with the minimum number of side effects in the minimum number of patients must be the desire of all clinical investigators who wish to generate new facts and contribute to the pool of knowledge. Progress in cell therapy for cardiovascular disease has been hindered at both the preclinical and clinical stages, perhaps because the appropriate tools to address the pertinent questions have not been used. In this context, magnetic resonance imaging (MRI) has, by necessity, rapidly evolved as the ideal tool for surrogate end-point measurements in early-phase clinical trials. In this issue of Circulation , Ripa and colleagues1 have elegantly demonstrated the utility and maturation of this technology in their study of granulocyte colony-stimulating factor (G-CSF) as an adjunctive therapy to mechanical reperfusion after myocardial infarction. Article p 1983 Cardiovascular cell transplantation and cytokine mobilization originally began in clinical trials with the explicit goal of myocardial regeneration,2,3 but more recently, the emphasis has been focused on “remodeling attenuation” therapy, in which the presumed mechanism has shifted from the “replacement” capacity of transplanted cells to their “paracrine” effects.4 This thesis becomes more convincing given the lack of cardiomyogenic transdifferentiation demonstrated by adult hematopoietic stem cells.5 Despite the indistinct mechanism, the early-phase, nonrandomized clinical studies of G-CSF given after myocardial infarction demonstrated provocatively the potential efficacy of G-SCF administered as sole therapy.6,7 The study presented in this issue of …