Recent Advances in Cardiac Tissue Engineering for the Management of Myocardium Infarction

Myocardium Infarction (MI) is one of the foremost cardiovascular diseases (CVDs) causing death worldwide, and its case numbers are expected to continuously increase in the coming years. Pharmacological interventions have not been at the forefront in ameliorating MI-related morbidity and mortality. Stem cell-based tissue engineering approaches have been extensively explored for their regenerative potential in the infarcted myocardium. Recent studies on microfluidic devices employing stem cells under laboratory set-up have revealed meticulous events pertaining to the pathophysiology of MI occurring at the infarcted site. This discovery also underpins the appropriate conditions in the niche for differentiating stem cells into mature cardiomyocyte-like cells and leads to engineering of the scaffold via mimicking of native cardiac physiological conditions. However, the mode of stem cell-loaded engineered scaffolds delivered to the site of infarction is still a challenging mission, and yet to be translated to the clinical setting. In this review, we have elucidated the various strategies developed using a hydrogel-based system both as encapsulated stem cells and as biocompatible patches loaded with cells and applied at the site of infarction.

Blood Flow Modeling in Coronary Arteries: A Review

Atherosclerosis is one of the main causes of cardiovascular events, namely, myocardium infarction and cerebral stroke, responsible for a great number of deaths every year worldwide. This pathology is caused by the progressive accumulation of low-density lipoproteins, cholesterol, and other substances on the arterial wall, narrowing its lumen. To date, many hemodynamic studies have been conducted experimentally and/or numerically; however, this disease is not yet fully understood. For this reason, the research of this pathology is still ongoing, mainly, resorting to computational methods. These have been increasingly used in biomedical research of atherosclerosis because of their high-performance hardware and software. Taking into account the attempts that have been made in computational techniques to simulate realistic conditions of blood flow in both diseased and healthy arteries, the present review aims to give an overview of the most recent numerical studies focused on coronary arteries, by addressing the blood viscosity models, and applied physiological flow conditions. In general, regardless of the boundary conditions, numerical studies have been contributed to a better understanding of the development of this disease, its diagnosis, and its treatment.

Cell Sheet Comprised of Mesenchymal Stromal Cells Overexpressing Stem Cell Factor Promotes Epicardium Activation and Heart Function Improvement in a Rat Model of Myocardium Infarction

Cell therapy of the post-infarcted myocardium is still far from clinical use. Poor survival of transplanted cells, insufficient regeneration, and replacement of the damaged tissue limit the potential of currently available cell-based techniques. In this study, we generated a multilayered construct from adipose-derived mesenchymal stromal cells (MSCs) modified to secrete stem cell factor, SCF. In a rat model of myocardium infarction, we show that transplantation of SCF producing cell sheet induced activation of the epicardium and promoted the accumulation of c-kit positive cells in ischemic muscle. Morphometry showed the reduction of infarct size (16%) and a left ventricle expansion index (0.12) in the treatment group compared to controls (24–28%; 0.17–0.32). The ratio of viable myocardium was more than 1.5-fold higher, reaching 49% compared to the control (28%) or unmodified cell sheet group (30%). Finally, by day 30 after myocardium infarction, SCF-producing cell sheet transplantation increased left ventricle ejection fraction from 37% in the control sham-operated group to 53%. Our results suggest that, combining the genetic modification of MSCs and their assembly into a multilayered construct, we can provide prolonged pleiotropic effects to the damaged heart, induce endogenous regenerative processes, and improve cardiac function.

Abstract 13552: Clinical Relevance of Endogenous Tissue-plasminogen Activator in Patients With Aortic Valve Sclerosis

Introduction: Impaired fibrinolysis featuring elevated tissue plasminogen activator (t-PA) induces cardiovascular outcomes. Aortic valve sclerosis (AVSc) shares similar aspects of pathophysiology with atherosclerosis and correlates with adverse cardiovascular events. Hypothesis: We investigated whether endogenous t-PA is associated with AVSc and clinical outcomes of these patients. Methods: Plasma levels of t-PA were measured in 155 AVSc patients and 140 non-AVSc counterparts. The composite major adverse cardio-cerebral events (MACCE), including cardiovascular death, nonfatal myocardium infarction, stroke, and re-hospitalization because of heart failure or unplanned revascularization were recorded during follow-up in 143 patients with AVSc (median, 6.5 years). Expression of t-PA was detected in human aortic valves with and without sclerosis by immunochemical analysis. Results: Plasma t-PA was higher in patients with AVSc than in those without (median, 2163.10 pg/mL vs 1403.17 pg/mL, p < 0.001). After adjusting for confounding variables, t-PA level remained an independent risk factor for AVSc (OR=1.66, 95%CI: 1.18-2.34, P=0.004). Based on the optimal cut-off of 1787.8 pg/mL determined by X-tile program, AVSc patients with low t-PA displayed better survival free from MACCE than those with high t-PA (p=0.0018). After full adjustment, t-PA was independently associated with composite MACCE (HR=1.33, 95% CI: 1.07-1.66, p=0.009). The area under the curve of plasma t-PA for predicting composite MACCE within three years was 0.71(95%CI: 0.63-0.80). The expression of t-PA was three times higher in sclerotic compared to non-sclerotic aortic valves. Conclusions: Elevated endogenous t-PA in plasma may serve as an indicator of AVSc and is associated with poor clinical outcomes in patients with AVSc.

ASSOCIATION BETWEEN SINGLE POLYMORPHISM IN THE LOCUS RS17216473 OF THE GENE THAT ENCODES 5-LIPOXYGENASEACTIVATING PROTEIN AND RISK OF MYOCARDIAL INFARCTION

The aim: To study the association between A/A, G/A, A/A genotypes, alleles A, G of the SNP rs17216473 of the gene that encodes ALOX5AP and the risk of myocardial infarction within the Ukrainian population. Materials and methods: PCR in real time and the analysis to discriminate alleles were used. The statistical processing was carried out by χ2 criteria and by χ2 criteria with Yates correction. Results: For the first time the SNP rs17216473 of gene that encodes ALOX5AP has been established to be statistically significantly associated with the risk of myocardial infarction in Ukrainian population. The connection with genotype A/A was opposite to that with genotype G/G. That is, A/A contribution to myocardium infarction has been statistically significant whereas, G/G has been statistically significantly associated with the absence of myocardial infarction. G/A genotype has not been statistically significantly associated with myocardial infarction. It has also been established a statistically significant connection exists between the risk of myocardial infarction and the presence of allele A (minor allele) of the polymorphism. Allele G, however, has a statistically significant association with the absence of myocardial infarction. All humans-homozygotes with the minor allele A had suffered from myocardial infarction. In the control group, humans-homozygotes with the minor allele A were not found. Conclusions: Summarizing our obtained results, we assume the carriers of G/G genotype to have a minimal risk of myocardial infarction onset, the carriers of G/A genotype to have a moderate risk and the carriers of A/A to have a great risk.