Abstract 14651: Injection of Cardiac Stem Cells in Utero is Able to Improve Postnatal Cardiac Function in Mice With a Defect in Striated Preferentially Expressed Gene
Introduction: Myosin light chain kinases are proteins important for myocyte function, and the striated preferentially expressed gene (Speg) is a member of this family. Disruption of the Speg gene locus in mice leads to neonatal cardiomyopathy. Recent data also suggest that cardiac stem cells (CSCs) from Speg mutant mice have defects in clone formation, growth, and differentiation.
Hypothesis: Administration of wild-type CSCs in utero can rescue Speg mutant mice from cardiac dysfunction after birth.
Methods: c-kit+ CSCs were isolated from wild-type mice using fluorescence-activated cell sorting or magnetic beads. Exogenous CSCs were injected into hearts at embryonic day 13.5, using micro-ultrasound guidance, and echocardiograms were performed 6 hours after birth. Heart tissue was harvested after the functional assessment, and immunostaining was performed.
Results: Echocardiograms revealed that Speg mutant compared with wild-type mice had a significant decrease in left ventricular (LV) ejection fraction (EF: 41±2.1% versus 63±1.5%) and fractional shortening (FS: 18±1.1 versus 31±1.1). In mice receiving CSCs, their EF and FS increased to 62±3.6% and 31±2.3% respectively, not different from wild-type mice. While septal and LV posterior walls were thinner in Speg mutant mice, those receiving CSCs had wall thicknesses comparable to wild-type mice. Also, LV internal diameter and volume were increased in Speg mutant mice, but after receiving CSCs the mutant mice had LV dimensions analogous to wild-type mice. Histologic evaluation of Speg mutant hearts receiving CSCs showed engraftment throughout both ventricles, with marked tissue regeneration. Immunostaining in Speg mutant mice showed that many of the injected CSCs differentiated into cardiomyocytes, however a portion of the cells remained undifferentiated.
Conclusions: Injection of wild-type CSCs in utero is able to functionally rescue Speg mutant mice from heart failure in the immediate postnatal period. These exogenously administered CSCs are able to engraft and differentiate into cardiomyocytes, although some of the CSCs remain in the heart tissue in an undifferentiated state. These data suggest that injection of CSCs into Speg mutant mice in utero has a therapeutic impact postnatally.
- © 2013 by American Heart Association, Inc.