Endocardial delivery of bone marrow-derived mononuclear cells (BMMCs) in patients with severe ischemic heart failure

Background

Intra-myocardial injections of BMMCs have shown promising initial results regarding improvement in myocardial ischemia. Experimental models have depicted the potential of some cell phenotypes in differentiating into blood vessels. BMMCs are a heterogeneous cell subpopulation group and the individual contribution of each cell subpopulation to favorable clinical outcomes remains unclear.

Methods

Fourteen patients with end-stage ischemic heart failure (mean ejection fraction [EF] = 20%) were submitted to endocardial BMMC injections at targeted hibernated segments utilizing electromechanical mapping (MyoStar, Cordis, Miami Lakes, FL, USA). BMMCs phenotypes were determined utilizing flow cytometry (CD3, CD4, CD8, CD14, CD19, CD34, CD45, CD56 and HLA-DR). Clonogenic assays for fibroblast and granulocyte-macrophage colony forming units (CFU-F and CFU-GM) was also performed. We correlated the density (cells/mm², area determined by the Noga system) of each injected cell phenotype with the total reversibility defect (objectively quantified by ICON workstation; Siemens) using exact Pearson moment correlation.

Results

All 14 patients (2 females, 57 ± 10 years old) had multivessel disease and previous myocardial infarction. Cell viability analysis was greater than 90% (96.2 ± 4.9%). There was a significant reduction in total reversibility defect (from 15.15 ± 14.99% to 4.53 ± 10.61%, P = 0.022). Within the phenotypes studied, the only one that had a significant correlation with the improvement in myocardial perfusion was the density of the CFU-F subpopulation (P = 0.033, R = 0.6).

Conclusion

Within the limits of the studied group, these data highlight the relevance of quantitative cell phenotype analysis aimed to identify the subpopulations that could play a major role to obtain clinical improvement. The benefit of selection and/or expansion of BMMC subpopulations should be addressed by future studies.

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