Intrapericardial Delivery of APA-Microcapsules as Promising Stem Cell Therapy Carriers in an Experimental Acute Myocardial Infarction Model

The administration of cardiosphere-derived cells (CDCs) after acute myocardial infarction (AMI) is very promising. CDC encapsulation in alginate-poly-l-lysine-alginate (APA) could increase cell survival and adherence. The intrapericardial (IP) approach potentially achieves high concentrations of the therapeutic agent in the infarcted area. We aimed to evaluate IP therapy using a saline vehicle as a control (CON), a dose of 30 × 106 CDCs (CDCs) or APA microcapsules containing 30 × 106 CDCs (APA-CDCs) at 72 h in a porcine AMI model. Magnetic resonance imaging (MRI) was used to determine the left ventricular ejection fraction (LVEF), infarct size (IS), and indexed end diastolic and systolic volumes (EDVi; ESVi) pre- and 10 weeks post-injection. Programmed electrical stimulation (PES) was performed to test arrhythmia inducibility before euthanasia. Histopathological analysis was carried out afterwards. The IP infusion was successful in all animals. At 10 weeks, MRI revealed significantly higher LVEF in the APA-CDC group compared with CON. No significant differences were observed among groups in IS, EDVi, ESVi, PES and histopathological analyses. In conclusion, the IP injection of CDCs (microencapsulated or not) was feasible and safe 72 h post-AMI in the porcine model. Moreover, CDCs APA encapsulation could have a beneficial effect on cardiac function, reflected by a higher LVEF at 10 weeks.

Overexpression of Long Noncoding RNA PTENP1 Inhibits Cell Proliferation and Migration via Suppression of miR-19b in Breast Cancer Cells

This study aimed to investigate the effect of long noncoding RNA PTENP1 in the development of breast cancer (BC). Quantitative real-time PCR was utilized to determine the expression of PTENP1 in tissues and cell lines. pcDNA3.1 and shRNA were used to over- and low-express PTENP1 in BC cell lines, and miR-19b mimic and inhibitor were utilized to over- and low-express miR-19b. Then the abilities of cell survival, apoptosis, migration, and invasion were assessed in BC cells with different expression levels of PTENP1 and miR-19b. The expression of PTENP1 was significantly downregulated in both BC tissues and cell lines. Overexpressed PTENP1 could significantly increase cell survival, colony forming, migration, and invasion but decrease apoptosis in BC cell lines. However, overexpressed miR-19b performed contrary effects compared with PTENP1 on cell survival, colony forming, migration, invasion, and apoptosis in BC cell lines. miR-19b can be downregulated by PTENP1, and the effect of overexpressed PTENP1 on the PI3k/Akt pathway could be aborted by overexpressed miR-19b. PTENP1 performed a negative role in the development of BC via downregulating miR-19 probably through the PTEN/PI3K/Akt pathway.

Improving stem cell engraftment to enhance functional efficacy in cardiovascular disease: where are we now?

Stem cell therapy is a promising therapy for repairing damaged tissue. A growing body of research shows that stem cells work effectively in several diseases such as cardiovascular disease, hepatic disease, and diabetes. It has been shown that stem cells not only differentiate into functional cells and replace dead cells, but also release growth factors and cytokines which can recruit autologous cells. The most significant barrier to achieve clinical relevance of this treatment mode is the poor survival rate of injected cells. To improve transplantation and enhance functional outcome, investigations of gene transfection (overexpression of anti-apoptotic and antioxidant proteins), growth factor supplementation, and scaffolding matrices are being conducted. In this review, we will focus on methods to increase cell survival in stem cell transplantation as a novel treatment for cardiovascular disease.

Estradiol abolishes reduction in cell death by the opioid agonist Met5-enkephalin after oxygen glucose deprivation in isolated cardiomyocytes from both sexes

There is evidence for differences in the response to the treatment of cardiovascular disease in men and women. In addition, there are conflicting results regarding the effectiveness of pharmacologically induced protection or ischemic preconditioning in females. We investigated whether the ability of Met5-enkephalin (ME) to reduce cell death after oxygen-glucose deprivation (OGD) is influenced by the presence of 17β-estradiol (E2) in a nitric oxide (NO)- and estrogen receptor-dependent manner. On postnatal day 7 to 8, murine cardiomyocytes from wild-type or inducible NO synthase (iNOS) knockout mice were separated by sex, isolated by collagenase digestion, cultured for 24 h, and subjected to 90 min OGD and 180 min reoxygenation at 37°C ( n = 4 to 5 replicates). Cell cultures were incubated in E2 for 15 min or 24 h before OGD. ME was used to increase cell survival. Cell death was assessed by propidium iodide. More than 300 cells were examined for each treatment. Data are presented as means ± SE. As a result, in both sexes, ME-induced cell survival was lost in the presence of E2, and the ability of ME to improve cell survival was restored after treatment with the estrogen receptor antagonist ICI-182780. Furthermore, iNOS was necessary for ME to increase cell survival following OGD in vitro. We conclude that ME-induced reduction in cell death is abolished by E2 in a sex-independent manner via activation of estrogen receptors, and this interaction is dependent on iNOS.

The Role of Leukotriene Receptor Signaling in Inflammation and Cancer

Leukotrienes (LTs) and prostaglandins (PGs) are metabolites of arachidonic acid that play major roles in various inflammatory conditions. The release of these mediators, by cells recruited to or present at the site of inflammation, modulate/influence the magnitude of the inflammatory response. A better understanding of eicosanoids and how their receptors trigger intracellular signaling during inflammatory conditions is helping to elucidate the well-known connection between chronic inflammatory disease and neoplastic transformation. In the current review, we summarize the role of LTs and PGs in chronic inflammation and, in particular, we focus on recent insights into the role of CysLT1receptor signaling pathway. In addition, we delineate how continuous CysLT1receptor activation and signaling can increase cell survival and proliferation as important early steps toward oncogenicity.