Abstract
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 10 6 ,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.
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