Development of composite functional tissue sheets using hiPSC-CMs and hADSCs to improve the cardiac function after myocardial infarction.

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been widely used in therapy of ischemic heart disease. However, there are still remaining issues that limit the therapeutic efficacy, such as immune rejection and low retention of hiPSC-CMs. Human adipose mesenchymal stromal cells (hADSCs) have been reported to be able to regulate the immune response, promote angiogenesis and promote the maturation of hiPSC-CMs. In this study, we co-cultured these two types of cells on fiber scaffold made of biodegradable poly (D,L-lactic-co-glycolic acid) (PLGA) polymer for several days to develop a composited 3D cardiac tissue sheet. As expected, the cells formed 231.00 ± 15.14 µm thickness tissue, with improved organization, alignment, ECM condition, contractile ability, and paracrine function compared to culture hiPSC-CMs only on PLGA fiber. Furthermore, the composited 3D cardiac tissue sheet significantly promoted the engraftment and survival after transplantation. The composited 3D cardiac tissue sheet also increased cardiac function, attenuated ventricular remodeling, decreased fibrosis, and enhanced angiogenesis in rat myocardial infarction model, indicating that this strategy wound be a promising therapeutic option in the clinical scenario.

Development of a thick and functional human adipose-derived stem cell tissue sheet for myocardial infarction repair in rat hearts.

BACKGROUND: Heart failure (HF) is a major cause of death worldwide. The most effective treatment for HF is heart transplantation, but its use is limited by the scarcity of donor hearts. Recently, stem cell-based therapy has emerged as a promising approach for treating myocardial infarction. Our research group has been investigating the use of human induced pluripotent stem cell-derived cardiomyocyte patches as a potential therapeutic candidate. We have successfully conducted eight cases of clinical trials and demonstrated the safety and effectiveness of this approach. However, further advancements are necessary to overcome immune rejection and enhance therapeutic efficacy. In this study, we propose a novel and efficient technique for constructing mesenchymal stem cell (MSC) tissue sheets, which can be transplanted effectively for treating myocardial infarction repair. METHODS: We applied a one-step method to construct the human adipose-derived mesenchymal stem cell (hADSC) tissue sheet on a poly(lactic-co-glycolic acid) fiber scaffold. Histology, immunofluorescence, and paracrine profile assessment were used to determine the organization and function of the hADSC tissue sheet. Echocardiography and pathological analyses of heart sections were performed to evaluate cardiac function, fibrosis area, angiogenesis, and left ventricular remodeling. RESULTS: In vitro, the hADSC tissue sheet showed great organization, abundant ECM expression, and increased paracrine secretion than single cells. In vivo, the hADSC tissue sheet group demonstrated improved cardiac functional recovery, less ventricular remodeling, decreased fibrosis, and enhanced angiogenesis than the MI group. CONCLUSIONS: We developed thick and functional hADSC tissue sheets via the one-step strategy. The hADSC tissue sheet showed excellent performance in treating myocardial infarction in the rat model.

Subtyping of hepatocellular adenoma: a machine learning-based approach.

Subtyping of hepatocellular adenoma (HCA) is an important task in practice as different subtypes may have different clinical outcomes and management algorithms. Definitive subtyping is currently dependent on immunohistochemical and molecular testing. The association between some morphologic/clinical features and HCA subtypes has been reported; however, the predictive performance of these features has been controversial. In this study, we attempted machine learning based methods to select an efficient and parsimonious set of morphologic/clinical features for differentiating a HCA subtype from the others, and then assessed the performance of the selected features in identifying the correct subtypes. We first examined 50 liver HCA resection specimens collected at the University of Washington and Kobe University/Kings College London, including HNF1α-mutated HCA (H-HCA) (n = 16), inflammatory HCA (I-HCA) (n = 20), beta-catenin activated HCA (ß-HCA) (n = 8), and unclassified HCA (U-HCA) (n = 6). Twenty-six morphologic/clinical features were assessed. We used LASSO (least absolute shrinkage and selection operator) to select key features that could differentiate a subtype from the others. We further performed SVM (support vector machine) analysis to assess the performance (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy) of the selected features in HCA subtyping in an independent cohort of liver resection samples (n = 20) collected at the University of Wisconsin-Madison. With some overlap, different combinations of morphologic/clinical features were selected for each subtype. Based on SVM analysis, the selected features classified HCA into correct subtypes with an overall accuracy of at least 80%. Our findings are useful for initial diagnosis and subtyping of HCA, especially in clinical settings without access to immunohistochemical and molecular assays.

Off-pump versus on-pump coronary artery bypass grafting for octogenarians: A meta-analysis involving 146 372 patients.

There is an ongoing debate concerning the optimal surgical option of myocardial revascularization for octogenarians. The current meta-analysis aimed to compare clinical outcomes following off-pump coronary artery bypass grafting (OPCABG) or conventional coronary artery bypass grafting (CCABG) in octogenarians. PubMed, Cochrane, Web of Science, and EMBASE databases were searched to identify eligible studies from inception to March 2021. The analysis was performed using STATA 15.1. A literature search yielded 18 retrospective studies involving 146 372 patients (OPCABG = 44 522 vs. CCABG = 101 850). Pooled analysis showed a strong trend toward reducing mortality risk in the OPCABG group (odds ratio: 0.75, 95% confidence interval: 0.56-1.00, p = .05). However, it did not reach statistical significance. The sensitive analysis demonstrated that OPCABG was less likely to cause death than CCABG. There were comparable data in myocardial infarction, renal failure, deep sternal wound infection, and hospital stays between the two groups, although the incidence of stroke, atrial fibrillation, prolonged ventilation, and reoperation for bleeding was significantly lower in the OPCAGB group. OPCABG may be an effective surgical strategy for myocardial revascularization, especially in reducing the incidence of postoperative stroke, atrial fibrillation, prolonged ventilation, and reoperation for bleeding.

Resveratrol activates PI3K/AKT to reduce myocardial cell apoptosis and mitochondrial oxidative damage caused by myocardial ischemia/reperfusion injury.

Resveratrol is a kind of iPolyphenols widely existing in herbal medicine. Here we aim to investigate whether resveratrol can reduce the degree of myocardial ischemia/reperfusion (IR) injury and inhibit the development of oxidative stress, and elucidate the molecular mechanism of resveratrol in protecting myocardial cells. The primary rat cardiomyocytes were used to establish an ischemia/reperfusion model in vitro, and a series of routine biochemical experiments were conducted to explore the antioxidant and anti-apoptotic effects of resveratrol in myocardial ischemia-reperfusion injury. Compared with that of the simulated ischemia-refusion (SIR) group, cell viability in the SIR and resveratrol co-treatment groups increased significantly (P < 0.001), the release of lactate dehydrogenase (LDH) and creatine kinase MB (CKMB) decreased, the positive rate of reactive oxygen species (ROS) in cardiomyocytes decreased, and the concentration of catalase and glutathione peroxidase increased significantly (P < 0.001). Besides, resveratrol can activate PI3K/AKT signaling pathway. PI3K siRNA can inhibit the PI3K/AKT signaling mediated by resveratrol. The addition of resveratrol can significantly increase the activity of mitochondrial superoxide dismutase (SOD) and reduce the malondialdehyde (MDA), which indicates that the oxidative damage of mitochondria induced by resveratrol was significantly weakened. The mitochondrial functional changes induced by resveratrol can be reversed by PI3K siRNA. In conclusion, our study shows that resveratrol can reduce ROS in cardiomyocytes by PI3K/AKT signaling pathway activation, and effectively inhibit the apoptosis of cardiomyocytes, thus having a direct protective effect on cardiomyocytes under SR.