Abstract 19913: Oxygen Concentration Modulates Human Cardiac Stem Cell Proliferation and Migration
Introduction: Cardiac Stem cells (CSCs) are currently being tested for their efficacy in the treatment of heart failure (HF). However, numerous factors are known to cause significant impairment to the exogenously delivered cell’s survival and regenerative capabilities. Hypoxia is one such stress that is known to contribute to inadequate tissue repair. Here, we test the hypothesis that hypoxia impairs cell proliferation, survival, and migration of human CSCs.
Methods and Results: CSCs were expanded from endomyocardial biopsies from patients and selected for CD117 expression. Cultured at standard room air (21% O2), CSCs were transferred to either physiologic (5%) or hypoxic (0.5%) conditions to assess the effect on cell proliferation, survival, and migration. Compared to both room air and hypoxia, the physiological O2 elevated both proliferation (P<0.05) and migration (2.34-fold, P<0.05) but did not affect cell survival. Furthermore, to investigate the potential use of a cell product to enhance hCSC migration under hypoxic conditions, hCSCs were exposed to conditioned media from hCSC or human MSCs. Upon the addition of the MSC conditioned stimulus, the migration of hCSCs was enhanced in hypoxic O2 to a level comparable to physiologic migration (2-fold, P<0.05 relative to CSC media control). In addition, hypoxia significantly reduced markers of replicative senescence, beta-galactosidase (β-Gal) (P<0.05) and P16INK4a (P<0.005), and decreased mitochondrial content (P<0.005). Lastly, SIRT1 protein and gene expression increased in physiological O2 (1.4-fold, P<0.005) and SDF-1 expression decreased in hypoxia (-1.75-fold P<0.05), which may account at least in part for the modulatory effects of O2 concentration.
Conclusions: Relative to hyperoxia and hypoxia, physiological O2 concentration promotes cell proliferation and migration. This study provides novel insights into the modulatory effects of O2 concentration on CSC biology and hasve important implications for refining stem cell therapies.
Author Disclosures: M.A. Bellio: None. C.O. Rodrigues: None. A. Landin: None. K.E. Hatzistergos: None. K. Valasaki: None. A. Khan: None. J.M. Hare: Ownership Interest; Significant; Dr. Hare reported having a patent for cardiac cell-based therapy. He holds equity in Vestion and maintains a professional relationship with Vestion as a consultant and member of the Board of Directors. I.H. Schulman: None.
- © 2016 by American Heart Association, Inc.