Mesenchymal stem cells improve cardiac recovery via immunomodulation in heart attack model

A pre-clinical study demonstrated that intravenous injection of ischemia-tolerant mesenchymal stem cells grown under chronic hypoxic conditions improves cardiac function in a mouse model of acute myocardial infarction via systemic anti-inflammatory effects.

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Aug 30, 2016
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Data presented at the 2016 European Society of Cardiology Congress in Rome, Italy, carried out by Washington Hospital Center (DC, USA) and CardioCell (San Diego, CA, USA), has demonstrated that intravenous injection of mesenchymal stem cells grown under chronic hypoxia (itMSCs) improves cardiac recovery in a murine model of acute myocardial infarction by suppressing the damaging immune response to injury.

“Since itMSCs secrete factors that have marked anti-inflammatory effects, we designed a study to determine if intravenously administered itMSCs can improve cardiac function following an AMI and, if so, whether such improvement is partially mediated by systemic anti-inflammatory activities,” explained Stephen Epstein, Director, Translational and Vascular Biology Research at MedStar Heart and Vascular Institute (based at Washington Hospital Center).

In the first study, 1 × 106 human itMSCs grown chronically at 5% O2 were injected into the tail vein of CD1 male mice 24 h after they underwent 45 min of left anterior descending artery occlusion, and heart imaging was performed a day later. In the next study, the animals underwent baseline echocardiography followed by MI surgery, then 24 h after infarction were randomized to receive either injection with 2 × 106 itMSCs or saline control. Echocardiography was repeated at days 3, 7 and 21, and blood, spleen and hearts were then harvested.

The radiolabeled stem cells were found to traffic to regions of myocardial infarction and prevent the deterioration in left ventricular function and reduce the significant adverse remodeling that occurs in mice with large infarcts, thereby improving recovery. Specifically, in large vs small infarcts, end systolic volume was 41 ± 8 vs 35 ± 4 ul (p = 0.53) and end diastolic volume was 79 ± 8 ul vs 70 ± 6 ul (p = 0.47), showing that itMSCs prevented the significant adverse left ventricular remodeling the occurrs with large infarcts. In addition, wall thickness was greater in the itMSC group compared with the control group. Few of the cells engrafted to the myocardium, however trafficking in the control group without infarction was minimal.

Furthermore, the cells were found to suppress splenic NK cells and modulate the damaging inflammatory response that develops after myocardial injury: itMSC injection resulted in 2.6 ± 0.13 splenic NK cells compared with 3.4 ± 0.36 in placebo (p < 0.04). In vitro transwell experiments analyzing antibody-induced reduction in NK cells demonstrated the same benefit, and therefore identified the itMSCs as being the cause of the myocardial recovery through paracrine effects suppressing NK cell proliferation.

Epstein concluded: “itMSC administration indeed improves cardiac function, and the itMSCs achieve this – at least, in part, – by their anti-inflammatory effects and abilities to decrease NK cells. These findings can profoundly impact future strategies for treating patients with AMI.”

Source: http://stemcardiocell.com/news/2016/08/29/european-society-of-cardiology-esc-congress-presentation-reveals-results-from-pre-clinical-study-using-cardiocells-stem-cells-for-acute-myocardial-infarction-ami/?elqTrackId=d4454b1680554337b2b19b7cf9469c34&elq=40f9ded27a20460f9090c4cce6156445&elqaid=16577&elqat=1&elqCampaignId=6


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Alexandra Thompson

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