Abstract 16354: Improved Myocardial Function in Patients with Chronic Ischemic Heart Disease Treated with Transendocardial Delivery of Bone Marrow Mononuclear Cells Depends Upon Input Cell Phenotype and Function
Background: Outcome after treatment of chronic ischemic cardiomyopathy (CM) with autologous bone marrow mononuclear cells (BMCs) depends on cell characteristics; however, the precise cell types critical to improved outcomes have yet to be defined. The FOCUS study demonstrated LVEF improved at 6 months, with a trend toward improved LVESV and maximal oxygen consumption (VO2max). As previously reported, increased levels of CD133+ and CD34+ progenitor cells (PCs) were also associated with improved LVEF. Additionally, higher levels of endothelial colony forming cells (ECFC) were associated with greater cell therapy effect on VO2max. The CCTRN Biorepository further evaluated relationships between BMC characteristics and LV outcomes of 88 ischemic CM patients with no revascularization option treated in the FOCUS trial.
Methods: Forty progenitor, hematopoietic and vascular cell phenotypes (CD31+, 34+, 133+, 45+, 3+, 19+, 11b+, 14+, and CXCR4) were measured, alone and in combination. A prospectively declared analysis plan assessing the relationship between cell phenotypes and patient outcomes using regression analysis was executed.
Results: Each 1% higher level of CD19+/CD11b+ cells in bone marrow was associated with 3.17% greater absolute unit increase in LVEF and 15.4 ml decrease in LVESV in the BMC group (Table). Each 1% increase in CD133+/CD34+ PCs was associated with a 3.34 ml decrease in LVESV (Table).
Conclusions: Increases in the double positive populations CD19+/CD11b+ and CD133+/CD34+ were associated with increased LV function in the BMC group. These data reinforce the importance of input BMC product composition, and suggest both PC and non-PC cells determine clinical outcome among patients with chronic ischemic CM. Understanding contributions of B-lymphocytes in the response of these patients to injury, disease, and treatment is a new direction generated by these data. Perhaps consideration should be given to non-progenitor as well as progenitor cell types when undertaking cell therapy.
- © 2012 by American Heart Association, Inc.