Abstract 20772: Antiarrhythmic Effect of Mesenchymal Stem Cells in Myocardial Infarction is Dependent on Surrounding Environment Through Altered Paracrine Action
Background: Mesenchymal stem cells (MSCs) can provide paracrine factor support for other cells in injured myocardium. We hypothesized that anti-arrhythmic effect of MSCs might depend on the environment through different paracrine action.
Methods: Sham (n=23), paracrine media (PM) secreted from MSCs under hypoxia (hypoxic PM group, n=12), PM secreted under normoxia (normoxic PM group, n=14) were administrated at border zone in rats with MI. At 7–10 days, we performed optical mapping, histological analysis, immunostaining, measurement of cytosolic free Ca2+, RT-PCR, and proteomics analysis.
Results: Survival curves revealed a marked reduction of sudden deaths in hypoxic PM, compared to normoxic PM (8.3% in hypoxic PM vs. 35.7% in normoxic PM, p=0.1) and sham-operated group (8.3% in hypoxic PM vs. 52.2% in sham, p=0.016). In optical mapping, pacing protocol induced VT in 77.8 % of sham-operated (n=9), 14.3 % of hypoxic PM (n=7), and 50 % of normoxic PM group (n = 6). Conduction velocity (CV) was markedly restored in hypoxic PM treated lesion compared to normoxic PM treated lesion (0.8±0.1m/s vs. 0.37±0.09 m/s, p<0.05) and sham-injected lesion (0.1±0.1 m/s). The focal activity emanating from border zone was suppressed in hypoxic PM compared to normoxic PM (0% vs. 33.3 %, p<0.05) or sham group (55.6%). A decrease of fibrosis, restoration of connexin 43, alleviation of Ca2+ overload, and an increase of Ca2+ related protein expression underlay this electrophysiological alteration. It was identified to be mediated by substances such as bFGF, IGF-1, HGF and EF hand domain containing 2. To assess the cellular effect of MSCs, we compared MSCs -injected rats (m=24) with normoxic PM-treated rats (n=15) after 1hr injury and treatment. CV were similar in MSCs engrafted and normoxic PM treated lesions (0.42±0.1m/s in MSCs vs. 0.37±0.09 m/s in normoxic PM, p>0.05), but APD80 increased in MSCs-engrafted lesion (98±12 ms vs. 78±21ms, p<0.05). Survival showed no significant difference (75% in MSCs vs. 67% in normoxic PM, p>0.05).
Conclusions: PM secreted from MSCs showed different preventive effect in sudden death and arrhythmogenicity according to hypoxic or normoxic environment, suggesting that antiarrhythmic effect of MSCs may depend on the surrounding environment.
- © 2010 by American Heart Association, Inc.