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Intracoronary infusion of encapsulated glucagon-like peptide-1-eluting mesenchymal stem cells preserves left ventricular function in a porcine model of acute myocardial infarction.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Jong, Renate De Hout, Gerardus P. J. Van Houtgraaf, Jaco H. Kazemi, Kushan Wallrapp, Christine Lewis, Andrew L. Pasterkamp, Gerard Hoefer, Imo E. Duckers, Henricus J. |
| Copyright Year | 2014 |
| Abstract | BACKGROUND Engraftment and survival of stem cells in the infarcted myocardium remain problematic in cell-based therapy for cardiovascular disease. To overcome these issues, encapsulated mesenchymal stem cells (eMSCs) were developed that were transfected to produce glucagon-like peptide-1, an incretin hormone with known cardioprotective effects, alongside MSC endogenous paracrine factors. This study was designed to investigate the efficacy of different doses of intracoronary infusion of eMSC in a porcine model of acute myocardial infarction (AMI). METHODS AND RESULTS One hundred pigs were subjected to a moderate AMI (posterolateral AMI; n=50) or a severe AMI (anterior AMI; n=50), whereupon surviving animals (n=36 moderate, n=33 severe) were randomized to receive either intracoronary infusion of 3 incremental doses of eMSC or Ringers' lactate control. Cardiac function was assessed using invasive hemodynamics, echocardiography, and histological analysis. A trend was observed in the moderate AMI model, whereas in the severe AMI model, left ventricular ejection fraction improved by +9.3% (P=0.004) in the best responding eMSC group, because of a preservation of left ventricular end-systolic volume. Arteriolar density increased 3-fold in the infarct area (8.4±0.9/mm(2) in controls versus 22.2±2.6/mm(2) in eMSC group; P<0.001). Although not statistically significant, capillary density was 30% higher in the border zone (908.1±99.7/mm(2) in control versus 1209.0±64.6/mm(2) in eMSC group; P=ns). CONCLUSIONS eMSCs enable sustained local delivery of cardioprotective proteins to the heart, thereby enhancing angiogenesis and preserving contractile function in an animal AMI model. |
| File Format | PDF HTM / HTML |
| DOI | 10.1161/CIRCINTERVENTIONS.114.001580 |
| PubMed reference number | 25294400 |
| Journal | Medline |
| Volume Number | 7 |
| Issue Number | 5 |
| Alternate Webpage(s) | http://circinterventions.ahajournals.org/content/circcvint/7/5/673.full.pdf?download=true |
| Alternate Webpage(s) | https://doi.org/10.1161/CIRCINTERVENTIONS.114.001580 |
| Journal | Circulation. Cardiovascular interventions |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
