pkh-26 and Myocardial-Infarction

Recent preclinical studies have demonstrated that bone marrow (BM)-derived Muse cells have a homing mechanism to reach damaged cardiac tissue while also being able to reduce myocardial infarct size and improve cardiac function; however, the potential of BM-Muse cells to foster new blood-vessel formation has not been fully assessed. Up to date, adipose tissue (AT)-derived Muse cells remain to be studied in acute myocardial infarction (AMI). The aim of the present study was to analyze in vitro and in vivo the neovascularization capacity of AT-Muse cells while exploring their biodistribution and differentiation potential in a translational ovine model of AMI.. AT-Muse cells were successfully isolated from ovine adipose tissue. In adult sheep, one or more diagonal branches of the left anterior descending coronary artery were permanently ligated for thirty minutes. Sheep were randomized in two groups and treated with intramyocardial injections: Vehicle (PBS, n = 4) and AT-Muse (2x107 AT-Muse cells labeled with PKH26 Red Fluorescent Dye, n = 4). Molecular characterization showed higher expression of angiogenic genes (VEGF, PGF and ANG) and increased number of tube formation in AT-Muse cells group compared to Adipose-derived mesenchymal stromal cells (ASCs) group. At 7 days post-IAM, the AT-Muse group showed significantly more arterioles and capillaries than the Vehicle group. Co-localization of PKH26+ cells with desmin, sarcomeric actin and troponin T implied the differentiation of Muse cells to a cardiac fate; moreover, PKH26+ cells also co-localized with a lectin marker, suggesting a possible differentiation to a vascular lineage.. Intramyocardially administered AT-Muse cells displayed a significant neovascularization activity and survival capacity in an ovine model of AMI.

Topics: Adipocytes; Alprostadil; Animals; Myocardial Infarction; Sheep; Tissue Distribution

When introduced into the infarcted heart, bone marrow‑derived mesenchymal stem cells (MSCs) prevent the heart from deleterious remodeling and improve its recovery. The aim of the present study was to investigate the effects of Ginkgo biloba extract (EGb) 761 on the infarcted myocardium microenvironment following MSC transplantation. The established rat myocardial infarction (MI) model, with implanted PKH‑26 marked MSCs (1x105 cells), were randomly divided into two groups: The control group (injected with normal saline) and the EGb 761 treatment group (injected with 100 mg/kg/day EGb 761). The following indices for cardiac function, including the extent of inflammation, oxidative stress, MSC apoptosis and MSC differentiation were measured 1, 2 and 7 days after treatment. The anti‑inflammatory effect of EGb 761 was observed by histological examination. Compared with the respective control group, the malondialdehyde content significantly decreased and the superoxide dismutase, catalase and glutathione peroxidase activity significantly increased in the EGb761‑treated groups. In addition, the apoptotic index gradually decreased (P<0.05) with the extension of MI time in the EGb761-treated groups compared to the respective control groups, suggesting that EGb761 exhbits anti-oxidative effects. In addition, the level of the Fas protein was positively correlated with the implanted MSC apoptotic ratio. Following 7 days of MSC transplantation with EGb 761 treatment, the expression of cTnI in PKH26‑labeled MSCs was observed in the transplanted myocardium. Cardiac function, including the ejection fraction, left ventricular end‑systolic pressure and dp/dtmax significantly increased, and the left ventricular end diastolic diameters, left ventricular end‑diastolic volumes and left ventricular end‑diastolic pressure significantly decreased (P<0.05, vs. the control group). The results demonstrated that EGb 761 is important in improving cardiac function and the infarcted myocardium microenvironment. The present study indicated that the protective effects of EGb 761 on the infarcted myocardium may be mediated by improving the viability and the differentiation of the implanted MSCs into cardiomyocytes.

Topics: Animals; Apoptosis; Biomarkers; Blotting, Western; Cardiotonic Agents; Cell Differentiation; Cell Survival; Disease Models, Animal; Electrocardiography; fas Receptor; Ginkgo biloba; Inflammation; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Myocardial Infarction; Myocardium; Organic Chemicals; Oxidation-Reduction; Oxidative Stress; Plant Extracts; Rats; Rats, Sprague-Dawley; Ultrasonography

Transplantation of embryonic stem cells (ESCs) can improve cardiac function in treatment of myocardial infarction. The low rate of cell retention and survival within the ischemic tissues makes the application of cell transplantation techniques difficult. In this study, we used a temperature-responsive chitosan hydrogel (as scaffold) combined with ESCs to maintain viable cells in the infarcted tissue. Temperature-responsive chitosan hydrogel was prepared and injected into the infarcted heart wall of rat infarction models alone or together with mouse ESCs. The result showed that the 24-h cell retention and 4 week graft size of both groups was significantly greater than with a phosphate buffered saline control. After 4 weeks of implantation, heart function, wall thickness, and microvessel densities within the infarct area improved in the chitosan + ESC, chitosan, and ESC group more than the PBS control. Of the three groups, the chitosan + ESC performed best. Results of this study indicate that temperature-responsive chitosan hydrogel is an injectable scaffold that can be used to deliver stem cells to infarcted myocardium. It can also increase cell retention and graft size. Cardiac function is well preserved, too.

Topics: Acridine Orange; Animals; Cell Differentiation; Cell Line; Cell Survival; Chitosan; Embryonic Stem Cells; Female; Hydrogel, Polyethylene Glycol Dimethacrylate; Indoles; Injections; Mice; Microvessels; Myocardial Infarction; Neovascularization, Physiologic; Organic Chemicals; Propidium; Rats; Rats, Sprague-Dawley; Recovery of Function; Temperature; Ultrasonography

The clinical application of stem cell therapy for myocardial infarction will require the development of methods to monitor treatment and pre-clinical assessment in a large animal model, to determine its effectiveness and the optimum cell population, route of delivery, timing, and flow milieu.. To establish a model for a) in vivo tracking to monitor cell engraftment after autologous transplantation and b) concurrent measurement of infarct evolution and remodeling.. We evaluated 22 dogs (8 sham controls, 7 treated with autologous bone marrow monocytes, and 7 with stromal cells) using both imaging of 111Indium-tropolone labeled cells and late gadolinium enhancement CMR for up to12 weeks after a 3 hour coronary occlusion. Hearts were also examined using immunohistochemistry for capillary density and presence of PKH26 labeled cells.. In vivo Indium imaging demonstrated an effective biological clearance half-life from the injection site of ~5 days. CMR demonstrated a pattern of progressive infarct shrinkage over 12 weeks, ranging from 67-88% of baseline values with monocytes producing a significant treatment effect. Relative infarct shrinkage was similar through to 6 weeks in all groups, following which the treatment effect was manifest. There was a trend towards an increase in capillary density with cell treatment.. This multi-modality approach will allow determination of the success and persistence of engraftment, and a correlation of this with infarct size shrinkage, regional function, and left ventricular remodeling. There were overall no major treatment effects with this particular model of transplantation immediately post-infarct.

Topics: Analysis of Variance; Animals; Bone Marrow Transplantation; Cell Survival; Dogs; Female; Image Processing, Computer-Assisted; Indium Radioisotopes; Magnetic Resonance Imaging, Cine; Monocytes; Myocardial Infarction; Organic Chemicals; Stromal Cells; Tomography, Emission-Computed, Single-Photon; Transplantation, Autologous; Ventricular Dysfunction, Left