Abstract 17746: Variable and Decreased Clonogenic Activity of Autologous Bone Marrow in Cell Therapy Patients With Ischemic Heart Disease, and CD34 as a Biomarker for Clinical Outcomes: Results From the Cardiovascular Cell Therapy Research Network (CCTRN)
Background: Bone marrow (BM) cell therapy for ischemic heart disease has shown mixed results with some trials reporting modest improvements in left ventricular ejection fraction (LVEF) while others report no improvement. Reasons for these findings are not well understood and may relate to the characteristics of BM cells and fraction of stem/progenitor cells.
Methods and Results: In three CCTRN clinical trials (TIME, LateTIME, FOCUS) patients with ischemic heart disease and LV dysfunction (LVEF ≤ 45%), received autologous BM mononuclear cells via intracoronary (n=207) or intramyocardial (n=92) injection. LV function was measured before and six months after cell administration. BM samples were evaluated for cell phenotype by flow cytometry and cell function by clonogenic progenitor cell assays. The BM specimens (n=299) were found to consist of highly variable cell populations. Both CD34+ endothelial progenitor cell (EPC) colony number and multipotent mesenchymal stromal cell (MSC) colony number were significantly decreased among study subjects vs. healthy BM donors (N=9; p < 0.05). BM CD34+ cell percentage was decreased in patients 7 days after acute myocardial infarction (mean of 1.9% compared to 2.3-2.7% in other time cohorts; p < 0.05). Across all three CCTRN trials, an increased percentage of CD34+ cells in the BM, defined as > 2 standard deviations above the mean, was associated with greater improvement in LVEF vs. the others (+9.9% vs. +2.32%, P = 0.03, for the TIME and LateTIME trials; and +6.6% vs. -0.02%, p = 0.021 for the FOCUS trial).
Conclusions: The results show that i) the distribution of BM cells was highly variable, ii) colony formation was significantly lower for CCTRN study subjects vs. healthy donors, and iii) improvement of LVEF correlated with BM CD34+ percentage. The data provide a possible explanation for the minimal clinical improvement seen in autologous BM cell therapy trials and support the future selection of potent cell subsets and/or the possibility of reversing co-morbid BM impairment.
- © 2013 by American Heart Association, Inc.