Background: Acute myocardial infarction (AMI) and the ensuing ischemic heart disease are approaching an epidemic state. Limited stem cell retention following intracoronary administration has reduced the clinical efficacy of this novel therapy. Polymer based cell coating is biocompatible and has been shown to be safe. Here, we assessed the therapeutic utility of gelatin-based biodegradable cell coatings on bone marrow derived cell retention in ischemic heart.Methods: Gelatin based cell coatings were formed from the surface-mediated photopolymerization of 3% gelatin methacrylamide and 1% PEG diacrylate. Cell coating was confirmed using a multimodality approach including flow cytometry, imaging flow cytometry (ImageStream System) and immunohistochemistry. Biocompatibility of cell coating, metabolic activity of coated cells, and the effect of cell coating on the susceptibility of cells for engulfment were assessed using in vitro models. Finally, cell adhesion to extracellular matrix was assessed in vitro using a microfluidic device. Following myocardial infarction and GFP+ BM-derived mesenchymal stem cell transplantation, flow cytometric and immunohistochemical assessment of retained cells was performed.Results: Coated cells are viable and metabolically active with coating degrading within 72 hours in vitro. Importantly, cell coating does not predispose bone marrow cells to aggregation or increase their susceptibility to phagocytosis. In vitro and in vivo studies demonstrated no evidence of heightened immune response or increased phagocytosis of coated cells. Cell transplantation studies following myocardial infarction proved the improved retention of coated bone marrow cells compared to uncoated cells.

Background. Myocardial inflammation following acute ischemic injury has been linked to poor cardiac remodeling and heart failure. Many studies have linked myeloperoxidase (MPO), a neutrophil and inflammatory marker, to cardiac inflammation in the setting of acute coronary syndrome (ACS). However, the prognostic role of MPO for adverse clinical outcomes in ACS patients has not been well established. Methods. MEDLINE and Cochrane databases were searched for studies from 1975 to March 2018 that investigated the prognostic value of serum MPO in ACS patients. Studies which have dichotomized patients into a high MPO group and a low MPO group reported clinical outcomes accordingly and followed up patients for at least 30 days to be eligible for enrollment. Data were analyzed using random-effects model. Sensitivity analyses were conducted for quality control. Results. Our meta-analysis included 13 studies with 9090 subjects and a median follow-up of 11.4 months. High MPO level significantly predicted mortality (odds ratio (OR) 2.03; 95% confidence interval (CI): 1.40-2.94; P<0.001), whereas it was not significantly predictive of major adverse cardiac events and recurrent myocardial infarction (MI) (OR 1.28; CI: 0.92-1.77, P=0.14 and OR 1.23; CI: 0.96-1.58, P=0.101, respectively). Hypertension, diabetes mellitus, and age did not affect the prognostic value of MPO for clinical outcomes, whereas female gender and smoking status have a strong influence on the prognostic value of MPO in terms of mortality and recurrent MI (metaregression coefficient -8.616: 95% CI -14.59 to -2.633, P=0.0048 and 4.88: 95% CI 0.756 to 9.0133, P=0.0204, respectively). Conclusions. Our meta-analysis suggests that high MPO levels are associated with the risk of mortality and that MPO can be incorporated in risk stratification models that guide therapy of high-risk ACS patients.

Mesenchymal stem cell (MSC) therapy has been widely tested in clinical trials to promote healing post-myocardial infarction. However, low cell retention and the need for a large donor cell number in human studies remain a key challenge for clinical translation. Natural biomaterials such as gelatin are ideally suited as scaffolds to deliver and enhance cell engraftment after transplantation. A potential drawback of MSC encapsulation in the hydrogel is that the bulky matrix may limit their biological function and interaction with the surrounding tissue microenvironment that conveys important injury signals. To overcome this limitation, we adopted a gelatin methacrylate (gelMA) cell-coating technique that photocross-links gelatin on the individual cell surface at the nanoscale. The present study investigated the cardiac protection of gelMA coated, hypoxia preconditioned MSCs (gelMA-MSCs) in a murine myocardial infarction (MI) model. We demonstrate that the direct injection of gelMA-MSC results in significantly higher myocardial engraftment 7 days after MI compared to uncoated MSCs. GelMA-MSC further amplified MSC benefits resulting in enhanced cardioprotection as measured by cardiac function, scar size, and angiogenesis. Improved MSC cardiac retention also led to a greater cardiac immunomodulatory function after injury. Taken together, this study demonstrated the efficacy of gelMA-MSCs in treating cardiac injury with a promising potential to reduce the need for donor MSCs through enhanced myocardial engraftment.