Circulating Around the Tissue

> The battle of life is, in the most cases, fought uphill… > > Samuel SmilesClinical application of bone marrow–derived cell populations remains one of the most popular sources for the treatment of ischemic heart disease around the world. Studies initially reported by Orlic et al,1,2 described the exceptional ability of hematopoietic stem cells (HSCs) to transdifferentiate into cardiomyocytes and microvessels in the absence of cell fusion after cytokine stimulation, myocardial infarction (MI), and postadoptive transfer into the damaged heart. The cellular therapeutic research field has displayed hesitancies in establishing the regenerative capacity of hematopoietic cells, confounded by the streamlined use of bone marrow–derived cell types in clinical trials. In addition, there remain questions as to the efficacy of bone marrow–derived stem cells after suggested discrepancies during meta-analysis of clinical data end points obtained in the past decade.3 Nonetheless, as many studies that conclusively support bone marrow cell (BMC) transdifferentiation, there are an equal number of reports refuting significant de novo formation of cardiomyocytes from HSCs.4–7 In 2004, both Murry et al6 and Balsam et al8 did not observe transdifferentiation of CD45+/Lineage−/c-kit+ to the level that was reported by Orlic et al1,2 after direct injection in the infarcted myocardium. Balsam et al8 suggested an additional experimental model for analyzing the commitment of endogenous circulating stem cells after infarction injury using mouse parabiosis, the process of surgically joining 2 mice to promote shared blood circulation. A new study in this issue of Circulation Research suggests that the initial data from the study by Balsam et al8 underestimate the contribution of circulating cells to cardiomyocytes after injury because of the timing of surgical parabiosis relative to MI.Article, see p 633In the recent study …