Human Umbilical Cord Stem Cells in Chitosan Attenuate Myocardial Injury in Rat Cardiac Infarction

Abstract

Background: Myocardial infarction (MI) is the leading cause of cardiovascular deaths and disability in the industrialized world. Although stem cells have been injected into hearts to limit MI damage, < 4% of stem cells remain in the heart for > 1 hour due to myocardial contractility which causes the rapid egress of the stem cells through the cardiac veins and lymphatics. We hypothesized that stem cells in chitosan gels would remain longer in the heart and therefore be more beneficial in MI repair. Methods: 100 rats with MIs were divided into Control, Chitosan Gel, human umbilical cord stem cells (hUCBC), or hUCBC in Gel groups for MI injections. Echocardiograms were done before and at 2, 4, and 8 weeks after injections then random hearts were examined for infarct size and histopathology at each time. Results: Control infarcts averaged 25 ± 1%, 26.5 ± 1% and 27 ± 1% of the ventricular area at 2, 4, and 8 weeks. hUCBC in Gel infarcts were smaller than Control, Gel or hUCBC infarcts and averaged 13 ± 0.9%, 11 ± 0.9% and 11 + 0.9% (P < 0.001 vs. controls). hUCBC in Gel periinfarct thicknesses averaged 889 ± 10 μm at 4 weeks and were greater than other groups (P < 0.05). Arteriole densities in hUCBC in Gels averaged 6.3 ± 0.2/high power field and were greater than other Groups (P < 0.05). LV fractional shortening (FS) averaged 49 ± 1% prior to MI and decreased in Controls to 24 ± 1.1%, 16.8 ± 1.2%, and 19.9 ± 1.1%. hUCBC in Gel FS were greater than other groups and averaged 38 ± 1.0%, 38 ± 1.0%, and 39 ± 1.0 (P < 0.001 vs. controls). hUCBC in Gel LV diastolic diameters were smaller than Gel or hUCBC Groups, averaged 0.68 ± 0.05, 0.65 ± 0.03, and 0.64 ± 0.04 (P < 0.05 vs. controls), and were similar to normals. Conclusion: hUCBC in Chitosan Gel exceed Chitosan or hUCBC in decreasing MI size and LV remodeling and increasing peri-infarct ventricular thickness and neovascularization.