Stem cells are promising for the treatment of myocardial infarction (MI) and large animal models should be used to better understand the full spectrum of stem cell actions and preclinical evidences. In this study, bone marrow mesenchymal stem cells (BM-MSCs) were transplanted into swine heart ischemia model. To detect glucose metabolism in global left ventricular myocardium and regional myocardium, combined with assessment of cardiac function, positron emission tomography-computer tomography (PET-CT) and magnetic resonance imaging (MRI) were performed. To study the changes of glucose transporters and glucose metabolism-related enzymes and the signal transduction pathway, RT-PCR, Western-blot, and immunohistochemistry were carried out. Myocardium metabolic evaluation by PET-CT showed that mean signal intensity (MSI) increased in these segments at week 4 compared with that at week 1 after BM-MSCs transplantation. Moreover, MRI demonstrated significant function enhancement in BM-MSCs group. The gene expressions of glucose transporters (GLUT1, GLUT4), glucose metabolism-related enzymes phosphofructokinase (PFK), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) and 70-kDa ribosomal protein S6 kinase (p70s6k) in BM-MSCs injected areas were up-regulated at week 4 after BM-MSCs transplantation and this was confirmed by Western-blot and immunohistochemistry. In conclusions, BM-MSCs transplantation could improve cardiac function in swine MI model by activation of mTOR signal transduction pathway.

The differentiation of constrictive pericarditis (CP) from restrictive cariomyopathy (RCM) is often difficult. This study sought to determine the clinical utility of cardiovascular magnetic resonance imaging (CMR) for differentiating both these disorders. Twenty-three patients with surgically documented CP, 22 patients with RCM and 25 normal subjects were included in the study. CMR yielded information about cardiac morphology, function and tissue characteristics. The left (LA) and right atrial (RA) volume was calculated using the area-length method. The relative atrial volume ratio (RAR) was defined as the LA volume divided by RA volume. Receiver operating characteristic curve analysis was used to test the ability of different variables in differentiating CP from RCM. The maximal pericardial thickness in CP patients was significantly larger than in normal subjects and RCM patients. The RA volume index in RCM patients (90.5 ± 35.3 mL/m2) was significantly larger than in CP patients (71.4 ± 15.7 mL/m2, p = 0.006) and normal subjects (38.1 ± 9.0 mL/m2, p < 0.001). The LA volume index in RCM (96.0 ± 37.0 mL/m2) and CP patients (105.6 ± 25.1 mL/m2) was significantly larger than in normal subjects (39.5 ± 9.5 mL/m2, p < 0.001 for all). The RAR in CP patients (1.50 ± 0.29) was significantly larger than in RCM patients (1.12 ± 0.33, p < 0.001) and normal subjects (1.06 ± 0.20, p < 0.001). There were no differences between RCM patients and normal subjects in the RAR (p = 0.452). At a cut-off value of 1.32 for the RAR, the sensitivity was 82.6%, and the specificity was 86.4% in the detection of CP. Septal bounce was identified in 95.7% CP patients, in none of RCM patients and normal subjects. Late gadolinium enhancement (LGE) was present in 31.8% RCM patients and absence in all CP patients and normal subjects. CMR with LGE and RAR can facilitate differentiation of CP from RCM.

Poor cell engraftment and survival after transplantation limited the application of stem cell therapy. Synthetic biomaterials could provide an artificial microenvironment for stem cells, thereby improve cell survival and enhance the therapeutic efficiency of stem cells. We synthesized a hydrogel by conjugating C domain peptide of insulin-like growth factor-1 (IGF-1C) onto chitosan (CS-IGF-1C hydrogel). Human placenta-derived mesenchymal stem cells (hP-MSCs), which constitutively express a red fluorescent protein (RFP) and renilla luciferase (Rluc), were co-transplanted with CS-IGF-1C hydrogel into a murine hindlimb ischemia model. Transgenic mice expressing firefly luciferase (Fluc) under the promoter of vascular endothelial growth factor receptor 2 (VEGFR2-Luc) were used. Dual bioluminescence imaging (BLI) was applied for tracking the survival of hP-MSCs by Rluc imaging and the VEGFR2 signal pathway activation by Fluc imaging. To investigate the therapeutic mechanism of CS-IGF-1C hydrogel, angiographic, real-time PCR, and histological analysis were carried out. CS-IGF-1C hydrogel could improve hP-MSCs survival as well as promote angiogenesis as confirmed by dual BLI. These results were consistent with accelerated skeletal muscle structural and functional recovery. Histology analysis confirmed that CS-IGF-1C hydrogel robustly prevented fibrosis as shown by reduced collagen deposition, along with increased angiogenesis. In addition, the protective effects of CS-IGF-1C hydrogel, such as inhibiting H2O2-induced apoptosis and reducing inflammatory responses, were proved by in vitro experiments. Taken together, IGF-1Cs provides a conducive niche for hP-MSCs to exert pro-mitogenic, anti-apoptotic, and pro-angiogenic effects, as well as to inhibit fibrosis. Thus, the incorporation of functional peptide into bioscaffolds represents a safe and feasible approach to augment the therapeutic efficacy of stem cells.

The accurate segmentation of medical images is crucial to medical care and research; however, many efficient supervised image segmentation methods require sufficient pixel level labels. Such requirement is difficult to meet in practice and even impossible in some cases, e.g., rare Pathoma images. Inspired by traditional unsupervised methods, we propose a novel Chan-Vese model based on the Markov chain for unsupervised medical image segmentation. It combines local information brought by superpixels with the global difference between the target tissue and the background. Based on the Chan-Vese model, we utilize weight maps generated by the Markov chain to model and solve the segmentation problem iteratively using the min-cut algorithm at the superpixel level. Our method exploits abundant boundary and local region information in segmentation and thus can handle images with intensity inhomogeneity and object sparsity. In our method, users gain the power of fine-tuning parameters to achieve satisfactory results for each segmentation. By contrast, the result from deep learning based methods is rigid. The performance of our method is assessed by using four Computerized Tomography (CT) datasets. Experimental results show that the proposed method outperforms traditional unsupervised segmentation techniques.

Due to the low survival rate of cell transplantation, stem cell has not been widely used in clinical treatment of acute myocardial infarction (AMI). In this study, we immobilized the C domain peptide of insulin-like growth factor-1 on chitosan (CS-IGF-1C) to obtain bioactive hydrogel. The purpose was to investigate whether CS-IGF-1C hydrogel incorporated with human placenta–derived mesenchymal stem cells (hP-MSCs) can boost the survival of hP-MSCs and enhance their therapeutic effects. hP-MSCs, which continuously expressed green fluorescent protein (GFP) and firefly luciferase (Fluc), were transplanted with CS-IGF-1C hydrogel into a mouse myocardial infarction model. Cell survival was detected by bioluminescence imaging (BLI), and cardiac function was measured by echocardiogram. Real-time PCR and histological analysis were used to explore the therapeutic mechanism of CS-IGF-1C hydrogel. CS-IGF-1C hydrogel could induce the proliferation of hP-MSCs and exert anti-apoptotic effects in vitro. The Calcine-AM/PI staining results showed that hP-MSCs seeded on CS-IGF-1C hydrogel could protect neonatal mouse ventricular cardiomyocytes (NMVCs) against oxidative stress. It was observed by BLI that CS-IGF-1C hydrogel injected into ischemic myocardium could improve the survival rate of hP-MSCs. Histology analysis indicated that co-transplantation of the CS-IGF-1C hydrogel and hP-MSCs could increase angiogenesis, reduce collagen deposition, ameliorate left ventricular expanded, and further promote the recovery of cardiac function. Besides, we found that the inflammatory response was inhibited and the expression of apoptosis-related genes was downregulated by CS-IGF-1C hydrogel. CS-IGF-1C hydrogel provides a conducive microenvironment for cells and significantly boosts the survival of hP-MSCs in mouse myocardial infarction model, which suggest that it may be a potential candidate for prolonging the therapeutic effect of hP-MSCs during AMI.