Abstract

We utilized two separate techniques, human Umbilical Cord Blood Stem Cells (hUCBC) and chitosan hydrogels, to limit acute myocardial infarction size and LV remodeling. Human Umbilical Cord Blood Mononuclear Cells (hUCBC), contain hematopoietic and mesenchymal stem cells. Chitosan is a polysaccharide. Chitosan hydrogels are approved by the United States Food and Drug Administration for human use in drug delivery and are used in repair of skin, nerve, cartilage, and bone. Hydrogels made from chitosan are liquid at room temperature but form a gel matrix at body temperature. We permanently ligated the left anterior descending coronary artery of 100 rats and then randomly divided the rats into control, hUCBC, or chitosan gel treatments. Transthoracic echocardiograms were obtained on rats prior to infarction and then at two, four, and eight weeks after infarction. Hearts were harvested from randomly selected rats from each group at each time for infarct size. Wall thickness and neovascularization of the infarction border zone were determined at eight weeks after infarction. Infarct sizes in the controls, expressed as a percentage of total right plus left ventricular area, averaged 25 ± 1% at 2 weeks, 26.5 ± 1% at 4 weeks and 27 ± 1% at 8 weeks. Infarct sizes in the hUCBC Group averaged 16 ± 1% at two weeks and 14 ± 1% at 4 weeks and at 8 weeks (all p < 0.001 compared with controls) and in the Gel Group averaged 17 ± 1% at two weeks, 14.5 ± 0.9% at 4 weeks and 13.9 ± 0.8% at 8 weeks (all p < 0.01 compared with controls). There was no significant difference in infarct size between the hUCBC and the Gel group. Injection of hUCBC or Gel into infarct borders produced scars that were similar in thickness and 4-5 mm thicker than the control scars at 8 weeks (p < 0.01). LV fractional shortening decreased in controls from a normal value of 54 ± 1% and averaged 24 ± 1.1% at 2 weeks. 16.8 ± 1.2% at 4 weeks, and 19.9 ± 1.1% at 8 weeks (all p < 0.001 compared with normals). Fractional shortening in hUCBC Group averaged 33.1 ± 0.9 at 2 weeks, 33.5 ± 1.1% at 4 weeks, and 34 ± 0.9% at 8 weeks and in the Gel group averaged 31 ± 1% at 2 weeks, 32 ± 1.2% at 4 weeks and 32 ± 0.9 at 8 weeks (all p < 0.001 compared with controls). The LV End-Diastolic Diameter (LVED) increased in controls from a normal value of 0.61 ± 0.05 cm to 0.88 ± 0.03 cm at two weeks then 0.89 ± 0.01 cm at 4 weeks, and 0.92 ± 0.05 cm at 8 weeks (all p < 0.001 compared with normals). In contrast, LV end-diastolic diameters in the hUCBC and Gel Groups were 17 to 23% smaller between two and eight weeks after myocardial infarction (p < 0.05). There was no significant difference in the hemodynamic measurements between the hUCBC and Gel groups. Vessel density in the border zones of myocardial infarctions after 8 weeks were: 5.3 ± 0.4/HPF in the hUCBC treated rats and 4.5 ± 0.5/HPF in the Gel group in comparison with 3.0 ± 0.3/HPF in the DMEM treated rats (p < 0.01 compared with controls). We conclude that hUCBC and chitosan hydrogels produce similar and significant reductions in infarct size and LV remodeling and substantial increases in LV border zone wall thickness and vascularity.

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