Mesenchymal stem cells derived from epicardial adipose tissue reverse cardiac remodeling in a rabbit model of myocardial infarction.

OBJECTIVE: Myocardial infarction (MI) is one of the most important causes of death. MI-related tissue loss and cardiac remodeling may result in heart failure. Intramyocardial injection of mesenchymal stem cells derived from adipose tissues, in acute MI animal models, has shown promising regenerative capabilities. This study aimed to investigate the myocardial regenerative capacity of epicardial adipose tissue-derived mesenchymal stem cells (ADSCs) in a rabbit model of MI. MATERIALS AND METHODS: A rabbit model of MI was performed in three groups: a sham-operated group, a control group, and a treatment group. MI was induced by coronary artery ligation via thoracotomy in the first operation. Four weeks after the first operation, intramyocardial injections of phosphate-buffered saline (PBS; control group) or ADSCs (10×106 in 100 µL; treatment group) were performed in the peri-infarct zone. Four weeks after the second operation, rabbits were sacrificed for further analysis. RESULTS: A significant increase in ejection fraction (p<0.0001) was detected in the treatment group, along with a significant increase in vascular density (p<0.001) and a significant decrease in infarct size (p<0.05) compared to the control group. CONCLUSIONS: Epicardial adipose tissue is a rich source of mesenchymal stem cells, which can differentiate into cardiomyocytes, as well as having neoangiogenic properties. Due to its potential to ameliorate chronic ischemic changes in the heart, it may be preferable in cardiac regenerative cell therapies.

Mesenchymal stem cells increase antioxidant capacity in intestinal ischemia/reperfusion damage.

BACKGROUND: Mesenchymal stem cells (MSCs) may have beneficial effects in reversing intestinal damage resulting from circulatory disorders. The hypothesis of this study is that MSCs increase antioxidant capacity of small bowel tissue following intestinal ischemia reperfusion (I/R) damage. METHODS: A total of 100 rats were used for the control group and three experimental groups, as follows: the sham control, local MSC, and systemic MSC groups. Each group consisted of 10 animals on days 1, 4, and 7 of the experiment. Ischemia was established by clamping the superior mesenteric artery (SMA) for 45min; following this, reperfusion was carried out for 1, 4, and 7days in all groups. In the local and systemic groups, MSCs were administered intravenously and locally just after the ischemia, and they were investigated after 1, 4, and 7days. The superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (Gpx) activities, as well as malondialdehyde (MDA) and total protein levels, were measured. Histopathological analysis was performed using light and electron microscopy. The indicators of proliferation from the effects of anti- and pro-inflammatory cytokines were evaluated using immunohistochemistry. RESULTS: MDA was increased (P<0.05) in the sham control group and decreased (P<0.05) in the MSC groups. SOD, CAT, and Gpx were decreased in the local MSC group (P<0.05). The highest level of amelioration was observed on day 7 in the local MSC group via light and electron microscopy. It was found that the MSCs arrived at the damaged intestinal wall in the MSC groups immediately after injection. Pro-inflammatory cytokines interleukin-1ß (IL1ß), transforming growth factor-ß1 (TGFß1), tumor necrosis factor-α (TNFα), IL6, MIP2, and MPO decreased (P<0.05), while anti-inflammatory cytokines EP3 and IL1ra increased (p<0.05) in the local and systemic MSC groups. In addition, proliferation indicators, such as PCNA and KI67, increased (P<0.05) in the local and systemic MSC groups. CONCLUSIONS: Parallel to our hypothesis, MSC increases the antioxidant capacity of small bowel tissue after intestinal I/R damage. The MSCs migrated to the reperfused small intestine by homing and reduced oxidative stress via the effects of SOD, CAT, and Gpx, as well as reducing the MDA level; thus, they could increase antioxidant capacity of intestine and have a therapeutic effect on the damaged tissue. We think that this effect was achieved via scavenging of oxygen radicals, suppression of pro-inflammatory cytokines, and increasing the expression of anti-inflammatory cytokines.

Differentiation Potential of Mouse Embryonic Stem Cells into Insulin Producing Cells in Pancreatic Islet Microenvironment.

BACKGROUND: The differentiation capacity of embryonic stem cells (ESCs) has great promise for type-1 diabetes for cellular treatment. Therefore, different strategies have been reported so far for derivation of insulin producing cells (IPCs) from ESCs. Providing similar microenvironmental conditions as in vivo, functional differentiation of stem cells into desired cell types could be obtained in vitro. The aim of the present research was to utilize differentiation potential of ESCs to IPCs by co-culture with mouse pancreatic islets (mPIs) for the first time. METHODS: We present an in-direct differentiation protocol which compared with a conventional differentiation protocol. Novel in-direct co-culture differentiation protocol in which mPIs induced differentiation of ESCs into IPCs was used. This technique was compared with the chemical differentiation protocol that involved supplementing the differentiation media with specific growth factors. We analyzed differentiated cells in both groups by immune labelling, gene expression and protein secretion. RESULTS: IPCs were obtained with in-direct co-culture within 30 days. Differentiated ESCs were found to be positive for IPC specific markers, Pdx1, Insulin, C-peptide, Glut2 and MafA. The results of immunocytochemical and gene expression analysis showed higher differentiation efficiency in co-culture group than chemical differentiation group. These results were confirmed by the response assay to high glucose levels with ELISA for insulin. DISCUSSION: Our findings illustrate the significant effect of co-culture in different stages of differentiation and maturation of ESCs in vitro. We have developed an efficient and easy way to differentiate ESCs into IPCs, which possess similar characters of mature insulin positive cells.