Background-Recent trials have shown that intracoronary infusion of bone marrow cells (BMCs) improves functional recovery after acute myocardial infarction. However, whether this treatment is effective in heart failure as a consequence of remodeling after organized infarcts remains unclear. In this randomized trial, we assessed the hypothesis that direct intramyocardial injection of autologous mononuclear bone marrow cells during coronary artery bypass graft (CABG) could improve global and regional left ventricular ejection fraction (LVEF) at 4-month follow-up. Methods and Results-Twenty patients (age 64.8Ϯ8.7; 17 male, 3 female) with a postinfarction nonviable scar, as assessed by thallium (Tl) scintigraphy and cardiac magnetic resonance imaging (MRI), scheduled for elective CABG, were included. They were randomized to a control group (n ϭ10, CABG only) or a BMC group (CABG and injection of 60.10 6 Ϯ31.10 6 BMC). Primary end points were global LVEF change and wall thickening changes in the infarct area from baseline to 4-month follow-up, as measured by MRI. Changes in metabolic activity were measured by Tl scintigraphy and expressed as a score with a range from 0 to 4, corresponding to percent of maximal myocardial Tl uptake (4 indicates Ͻ50%, nonviable scar; 3, 50% to 60%; 2, 60% to 70%; 1, 70% to 80%; 0Ͼ80%). Global LVEF at baseline was 39.5Ϯ5.5% in controls and 42.9Ϯ10.3% in the BMC group (Pϭ0.38). At 4 months, LVEF had increased to 43.1Ϯ10.9% in the control group and to 48.9Ϯ9.5% in the BMC group (Pϭ0.23). Systolic thickening had improved from Ϫ0.6Ϯ1.3 mm at baseline to 1.8Ϯ2.6 mm at 4 months in the cell-implanted scars, whereas nontreated scars remained largely akinetic (Ϫ0.5Ϯ2.0 mm at baseline compared with 0.4Ϯ1.7 mm at 4 months, Pϭ0.007 control versus BMC-treated group at 4 months). Defect score decreased from 4 to 3.3Ϯ0.9 in the BMC group and to 3.7Ϯ0.4 in the control group (Pϭ0.18). Conclusions-At 4 months, there was no significant difference in global LVEF between both groups, but a recovery of regional contractile function in previously nonviable scar was observed in the BMC group.

We have identified a new human CSC population able to differentiate into functional CMs. This opens interesting perspectives for cell therapy in patients with ischaemic heart disease.

In the past, clinical trials transplanting bone marrow-derived mononuclear cells reported a limited improvement in cardiac function. Therefore, the search for stem cells leading to more successful stem cell therapies continues. Good candidates are the so-called cardiac stem cells (CSCs). To date, there is no clear evidence to show if these cells are intrinsic stem cells from the heart or mobilized cells from bone marrow. In this study we performed a comparative study between human mesenchymal stem cells (hMSCs), purified c-kit(+) CSCs, and cardiosphere-derived cells (CDCs). Our results showed that hMSCs can be discriminated from CSCs by their differentiation capacity towards adipocytes and osteocytes and the expression of CD140b. On the other hand, cardiac progenitors display a greater cardiomyogenic differentiation capacity. Despite a different isolation protocol, no distinction could be made between c-kit(+) CSCs and CDCs, indicating that they probably derive from the same precursor or even are the same cells.

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