Abstract 20957: Paracrine and Functional Superiority of Human Cardiosphere-Derived Cells as Compared to Mesenchymal Stem Cells, Adipose-Derived Stem Cells or Bone Marrow Mononuclear Cells
Background: Adult stem cells of different origins have been studied for repairing the damaged heart, but few direct comparisons have been made. Here we conducted a direct head-to-head comparison of four human stem cell types in vitro for paracrine potency, and in vivo in the same model of myocardial infarction.
Methods and Results: Human cardiosphere-derived stem cells (CDCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), adipose tissue-derived mesenchymal stem cells (AD-MSCs), and bone marrow mononuclear cells (BM-MNCs) were compared. FACS analysis revealed a distinctive antigenic profile for CDCs: 99.9% CD105+, 7.0% c-kit+, 18.4% CD90+, 1.0% CD34+, 0.99% CD133+, 0.62% CD31+, and 0.45% CD45+. In vitro, CDCs showed the greatest myogenic differentiation potency (by immunostaining for Troponin T; p<0.001), highest angiogenic potential (by tube formation assay; p<0.05), and the most balanced production of various angiogenic and anti-apoptotic factors under both normoxic (20% O2) and hypoxic (1% O2) conditions (Figure 1A-F). In vivo, injection of CDCs into the infarcted hearts of SCID mice resulted in the greatest improvement of cardiac function compared to vehicle-injected controls (n=8–17 for each cell type; p<0.001 by ANOVA), the highest cell engraftment and myogenic differentiation rates (p<0.05), and the least-abnormal heart morphology 3 wks after treatment (p<0.05). Also, the CDC-treated hearts exhibited the highest frequencies of Ki67- and c-kit-positive cells (p<0.05), and lowest number of apoptotic (TUNEL-positive) cells (p<0.001).
Conclusions: CDCs exhibit a balanced profile of paracrine factor production, and, among various comparator cell types, provide the best functional results for the treatment of experimental myocardial infarction.
- © 2010 by American Heart Association, Inc.