Improved conduction and increased cell retention in healed MI using mesenchymal stem cells suspended in alginate hydrogel

• DOI: 10.1007/s10840-014-9940-9
• Publication Date: 2014-09-18T03:46:11Z
• Authors: Nikhil C. Panda; Sean T. Zuckerman; Olurotimi O. Mesubi; David S. Rosenbaum; Marc S. Penn; J. Kevin Donahue; Eben Alsberg; Kenneth R. Laurita
• Keywords: 0301 basic medicine; Analysis of Variance; Microscopy, Confocal; Alginates; Swine; Hexuronic Acids; Cell Culture Techniques; Myocardial Infarction; Mesenchymal Stem Cell Transplantation; Echocardiography, Doppler; Hydrogel, Polyethylene Glycol Dimethacrylate; Disease Models, Animal; Electrocardiography; Random Allocation; 03 medical and health sciences; Treatment Outcome; Glucuronic Acid; Heart Conduction System; Reference Values; Animals; Electrophysiologic Techniques, Cardiac; Cells, Cultured

Mesenchymal stem cells (MSCs) have been associated with reduced arrhythmias; however, the mechanism of this action is unknown. In addition, limited retention and survival of MSCs can significantly reduce efficacy. We hypothesized that MSCs can improve impulse conduction and that alginate hydrogel will enhance retention of MSCs in a model of healed myocardial infarction (MI).Four weeks after temporary occlusion of the left anterior descending artery (LAD), pigs (n = 13) underwent a sternotomy to access the infarct and then were divided into two studies. In study 1, designed to investigate impulse conduction, animals were administered, by border zone injection, 9-15 million MSCs (n = 7) or phosphate-buffered saline (PBS) (control MI, n = 5). Electrogram width measured in the border zone 2 weeks after injections was significantly decreased with MSCs (-30 ± 8 ms, p < 0.008) but not in shams (4 ± 10 ms, p = NS). Optical mapping from border zone tissue demonstrated that conduction velocity was higher in regions with MSCs (0.49 ± 0.03 m/s) compared to regions without MSCs (0.39 ± 0.03 m/s, p < 0.03). In study 2, designed to investigate MSC retention, animals were administered an equal number of MSCs suspended in either alginate (2 or 1 % w/v) or PBS (n = 6/group) by border zone injection. Greater MSC retention and survival were observed with 2% alginate compared to PBS or 1% alginate. Confocal immunofluorescence demonstrated that MSCs survive and are associated with expression of connexin-43 (Cx43) for either PBS (control), 1%, or 2% alginate.For the first time, we are able to directly associate MSCs with improved impulse conduction and increased retention and survival using an alginate scaffold in a clinically relevant model of healed MI.