Abstract 10025: Human Umbilical Cord Stem Cells Increase Heart Contractility and Decrease Fibrosis in Congenital Cardiomyopathy
Introduction: We have established that human umbilical cord blood stem cells (hUCSC) decrease inflammation and infarct size in acute myocardial infarctions in rats. We hypothesized that hUCSC can limit the progressive LV fibrosis and LV failure that occurs in TO2 hamsters, a model of congenital cardiomyopathy due to sarcoglycan deficiency.
Methods: 22 TO2 1 month old hamsters were treated with intramyocardial (IM) hUCBC, 4х 106 ,in Isolyte®, and 23 TO2 1 month old hamsters were treated with IM Isolyte. 16 1 month old F1B hamsters served as controls and received IM Isolyte. No hamster was given immunosuppressive treatment. Echocardiograms were performed on all hamsters prior to and monthly after treatment for 6 months. Heart tissues were stained with hematoxylin and eosin, Masson’s Trichrome and human nuclear antibody.
Results: In the F1B hamsters, LV fractional shortening (FS) and ejection fractions (EF) did not significantly decrease over 6 months. In contrast, in Isolyte treated TO2 hamsters, FS decreased from 56.2±1.0% to 19.7±3.2% and EF decreased from 89.5±1.4% to 41.9 ±5.9% at 6 months (both p < 0.001). The FS and EF in hUCSC treated TO2 hamsters also progressively decreased over 6 months but changes were more gradual, especially during first month after hUCSC when FS was 52.0±1.5% and EF was 89.5±1.4%, which was not significantly different from the F1B hamsters. In the hUCSC treated hamsters, the FS and EF were 20-30% greater than FS and EF in Isolyte TO2 hamsters at 3 and 5 months (p < 0.01). Injection of hUCBC in a subset of Isolyte treated TO2s at 4 months increased LV EF at age 5 months to 57.5±2.3% compared with a EF of 41.6±3.1% (p< 0.01) in Isolyte treated TO2s. In Isolyte treated TO2s at 6-7 months, fibrosis involved 30.0±5.0% of LV and 35.0±5.0% of LV septum. In contrast, in hUCSC treated hamsters, fibrosis involved only 16.5± 2.3% of LV and 16.3±1.8% of septum (p< 0.05). The average number of blood vessels per myocardial microscopic field in hUCSC treated hearts was 53.5 ± 0.8 versus 46.2 ± 3.0 in Isolyte treated TO2 hearts (p < 0.05).
Conclusion: hUCSC, given as a single intramyocardial injection, can limit fibrosis and increase heart contractility over the short term in TO2 hamsters with congenital cardiomyopathy.
- Congenital Cardiomyopathy
- Left Ventricular Fibrosis
- Left Heart Failure
- Umbilical Cord Stem Cells
- Stem Cells
Author Disclosures: R. Henning: None. E. Jimenez: None.
- © 2015 by American Heart Association, Inc.