Abstract 260: Cardiosphere Derived Cells Generated from the Human Atria Exhibit Superior Potency Compared to the Left Ventricle

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
David L Simpson ◽  
Agnieszka Blusztajn ◽  
Ileana Valle ◽  
Michelle Kreke ◽  
Linda Marban ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Control Group ◽  
Cell Bank ◽  
Tissue Samples ◽  
Dna Microarray Data ◽  
Master Cell Bank ◽  
Normal Human ◽  
Minimal Treatment ◽  
Mdr 1

Currently, allogeneic cardiosphere-derived cells (CDCs) are being tested in a phase I/II clinical trial. Our manufacturing process utilizes the atria and other regions of the heart to build a master cell bank, but leaves the left ventricle (LV) intact thus eliminating a potential source to build our clinical stocks. In an effort to increase CDC yield per heart, we compared CDCs generated from the atria to the left ventricle (LV). To investigate this hypothesis we characterized CDCs by flow cytometry, growth kinetics and in vivo potency. The surface marker profiles for atrial CDCs and LV CDCs were very similar. Of the 17 markers used to characterize CDCs (c-kit, MDR-1, Sca-1, Abcg2, CD133, CD31, CD34, CD45, CD105, CD29, CD44, CD73, CD166, CD140b, CD90, DDR2 and α-SMA) only one demonstrated substantial differential expression in LV versus atria. PDGFR-β (CD140b) was upregulated in CDCs derived from the LV compared to the atria. Consistent with this finding, GEO2R analysis of DNA microarray data revealed increased PDGFR-β and PDGF-B expression in normal human LV tissue compared to atrial tissue. We have also observed that CDC expression of PDGFR-β negatively correlates with in vivo potency (R=0.899) suggesting that the high expression of this marker in CDCs derived from the LV may limit its regenerative performance. Indeed when calculated growth rates were compared, tissue samples from the atria yielded 4 to 6-fold more CDCs compared to the LV (atria=26±10 versus LV=5±5 Million CDCs/g/day). Also, CDCs derived from the atria and LV led to differential improvements in ejection fraction (EF) over three weeks. CDCs from the atria significantly outperformed the control group (atrial CDCs=Δ+12.6±10.8%, control=Δ-15.3±13.6%), while CDCs from the LV showed minimal treatment effects and failed to meet our minimal potency requirement (LV CDCs=Δ+0.0±6.2%). In conclusion, LV CDCs display limited potential for clinical use. This observation provides a unique opportunity to explore the mechanisms that govern functional potency and assist in understanding the basic processes involved in CDC mediated repair.

scholarly journals Are there attacking points in the eicosanoid cascade for chemotherapeutic options in benign meningiomas?

2007 ◽  
Vol 23 (4) ◽  
pp. E8 ◽  
Author(s):  
Christina Pfister ◽  
Rainer Ritz ◽  
Heike Pfrommer ◽  
Antje Bornemann ◽  
Marcos S. Tatagiba ◽  
...  
Keyword(s):  
World Health ◽  
Pcr Analysis ◽  
Prostaglandin E ◽  
Tissue Samples ◽  
Human Cortex ◽  
Normal Human ◽  
Cox 2 ◽  
Cox 1

Object The current treatment for recurrent or malignant meningiomas with adjuvant therapies has not been satisfactory, and there is an intense interest in evaluating new molecular markers to act as therapeutic targets. Enzymes of the arachidonic acid (AA) cascade such as cyclooxygenase (COX)–2 or 5-lipoxygenase (5-LO) are upregulated in a number of epithelial tumors, but to date there are hardly any data about the expression of these markers in meningiomas. To find possible targets for chemotherapeutic intervention, the authors evaluated the expression of AA derivatives at different molecular levels in meningiomas. Methods One hundred and twenty-four meningioma surgical specimens and normal human cortical tissue samples were immunohistochemically and cytochemically stained for COX-2, COX-1, 5-LO, and prostaglandin E receptor 4 (PTGER4). In addition, Western blot and polymerase chain reaction (PCR) analyses were performed to detect the presence of eicosanoids in vivo and in vitro. Results Sixty (63%) of 95 benign meningiomas, 21 (88%) of 24 atypical meningiomas, all five malignant meningiomas, and all normal human cortex samples displayed high COX-2 immunoreactivity. All cultured specimens and IOMM-Lee cells stained positive for COX-2, COX-1, 5-LO, and PTGER4. The PCR analysis demonstrated no changes in eicosanoid expression among meningiomas of different World Health Organization grades and in normal human cortical and dura mater tissue. Conclusions Eicosanoid derivatives COX-1, COX-2, 5-LO, and PTGER4 enzymes show a high universal expression in meningiomas but are not upregulated in normal human cortex and dura tissue. This finding of the ubiquitous presence of these enzymes in meningiomas offers an excellent baseline for testing upcoming chemotherapeutic treatments.

The effects of intravitreally injected bevacizumab on the retina and retina pigment epithelium: experimental in-vivo electron microscopic study in intact versus vitrectomized eyes

Open Medicine ◽  
2010 ◽  
Vol 5 (6) ◽  
pp. 745-751 ◽  
Author(s):  
Nilufer Kocak ◽  
Candan Ozogul ◽  
Suleyman Kaynak ◽  
Ulker Sonmez ◽  
Mehmet Zengin ◽  
...  
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Intravitreal Bevacizumab ◽  
Electron Microscopic Examination ◽  
Photoreceptor Cells ◽  
Control Group ◽  
Electron Microscopic ◽  
Tissue Samples ◽  
Electron Microscopes

AbstractTo analyze the retinal toxicity of bevacizumab at various doses both in vitrectomized and non-vitrectomized rabbit models. Twenty- eight rabbits were included in the study. Twenty- four rabbits were assigned to six groups, with 4 of the rabbits in the control group. The animals in Groups 1, 2 and 3 received bevacizumab at a dose of 0.3 mg, 0.5 mg and 1.5 mg /eye, respectively. The rabbits in Groups 4, 5 and 6 received intravitreal bevacizumab of 0.3 mg, 0.5 mg and 1.5mg/eye, respectively, after gas compression vitrectomy. Two weeks after the procedure, the rabbits were euthanized. Retina tissue samples were then obtained and examined with both light and electron microscopes. In Groups 1, 2 and 3 after bevacizumab injection, toxic degeneration in the photoreceptor and retinal pigment epithelium cells was observed via electron microscopic examination. The findings in Groups 4 and 5 were normal as compared to the control group. In Group 6, toxicity in the bipolar neurons and photoreceptor cells was noticed. Increased toxicity and retinal penetration were noticed in all administered doses of bevacizumab in the presence of vitreous. In addition, ocular toxicity occurred through the injection of the highest dose of bevacizumab after vitrectomy. It is possible that the bevacizumab dose and the, vitreous are as important as the drug half-life in the vitreous.

scholarly journals Mechanical Response Changes in Porcine Tricuspid Valve Anterior Leaflet Under Osmotic-Induced Swelling

2019 ◽  
Vol 6 (3) ◽  
pp. 70 ◽  
Author(s):  
Samuel D. Salinas ◽  
Margaret M. Clark ◽  
Rouzbeh Amini
Keyword(s):  
Tricuspid Valve ◽  
Soft Tissues ◽  
Mechanical Response ◽  
Ex Vivo ◽  
Control Group ◽  
Anterior Leaflet ◽  
Buffer Solution ◽  
Tissue Samples ◽  
The Impact

Since many soft tissues function in an isotonic in-vivo environment, it is expected that physiological osmolarity will be maintained when conducting experiments on these tissues ex-vivo. In this study, we aimed to examine how not adhering to such a practice may alter the mechanical response of the tricuspid valve (TV) anterior leaflet. Tissue specimens were immersed in deionized (DI) water prior to quantification of the stress–strain responses using an in-plane biaxial mechanical testing device. Following a two-hour immersion in DI water, the tissue thickness increased an average of 107.3% in the DI water group compared to only 6.8% in the control group, in which the tissue samples were submerged in an isotonic phosphate buffered saline solution for the same period of time. Tissue strains evaluated at 85 kPa revealed a significant reduction in the radial direction, from 34.8% to 20%, following immersion in DI water. However, no significant change was observed in the control group. Our study demonstrated the impact of a hypo-osmotic environment on the mechanical response of TV anterior leaflet. The imbalance in ions leads to water absorption in the valvular tissue that can alter its mechanical response. As such, in ex-vivo experiments for which the native mechanical response of the valves is important, using an isotonic buffer solution is essential.

scholarly journals Endogenous Estrogen-Mediated Heme Oxygenase Regulation in Experimental Menopause

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Anikó Pósa ◽  
Renáta Szabó ◽  
Anett Csonka ◽  
Médea Veszelka ◽  
Anikó Magyariné Berkó ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Heme Oxygenase ◽  
Protoporphyrin Ix ◽  
Control Group ◽  
St Segment ◽  
Female Wistar Rats ◽  
Endogenous Estrogen ◽  
Estrogen Depletion ◽  
Cardiac Left Ventricle

Estrogen deficiency is one of the main causes of age-associated diseases in the cardiovascular system. Female Wistar rats were divided into four experimental groups: pharmacologically ovariectomized, surgically ovariectomized, and 24-month-old intact aging animals were compared with a control group. The activity and expression of heme oxygenases (HO) in the cardiac left ventricle, the concentrations of cardiac interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α), the myeloperoxidase (MPO) activity in the cardiac left ventricle, and the effects of heme oxygenase blockade (by 24-hour and 1-hour pretreatment with tin-protoporphyrin IX, SnPP) on the epinephrine and phentolamine-induced electrocardiogram ST segment changesin vivowere investigated. The cardiac HO activity and the expression of HO-1 and HO-2 were significantly decreased in the aged rats and after ovariectomy. Estrogen depletion was accompanied by significant increases in the expression of IL-6 and TNF-α. The aged and ovariectomized animals exhibited a significantly elevated MPO activity and a significant ST segment depression. After pretreatment with SnPP augmented ST segment changes were determined. These findings demonstrate that the sensitivity to cardiac ischemia in estrogen depletion models is associated with suppression of the activity and expression of the HO system and increases in the secretion of proinflammatory cytokines and biomarkers.

Astatine-211 labelled a small molecule peptide: specific cell killing in vitro and targeted therapy in a nude-mouse model

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Weihao Liu ◽  
Yu Tang ◽  
Huan Ma ◽  
Feize Li ◽  
Yingjiang Hu ◽  
...  
Keyword(s):  
Small Molecule ◽  
Cell Killing ◽  
The Body ◽  
Control Group ◽  
Specific Cell ◽  
Step Method ◽  
Nude Mouse Model ◽  
Tissue Samples

AbstractExtensive interest in the development of α-emitting radionuclides astatine-211 (211At) stems from the potential superiority for the treatment of smaller tumors, disseminated disease, and metastatic disease. VP2, a small molecule fusion peptide, can specifically bind to the VPAC1 receptor which is over-expressed in malignant epithelial tumors. In our recent study, we performed the preparation of 211At labelled VP2 through a one-step method. In this work, we explored the targeted radionuclide therapy with [211At]At-SPC-VP2 in vitro and in vivo. The cytotoxicity and specific cell killing of [211At]At-SPC-VP2 were evaluated using the CCK-8 assay. Compared with the [211At]NaAt, the VPAC1-targeted radionuclide compound [211At]At-SPC-VP2 showed more effective cytotoxicity in vitro. Targeted radioactive therapy trial was carried out in non-small-cell lung cancer (NSCLC) xenograft mice. For the therapy experiment, 4 groups of mice were injected via the tail vein with 370 kBq, 550 kBq, 740 kBq, 3 × ∼246 kBq of [211At]At-SPC-VP2, of which the second and third injections were given 4 and 8 days after the first injection, respectively. As controls, animals were treated with saline or 550 kBq [211At]NaAt. The body weight and tumor size of mice were monitored before the administration and every 2 days thereafter. Cytotoxic radiation of partial tissue samples such as kidneys, liver and stomach of mice were assessed by immunohistochemical examination. The tumor growth was inhibited and significantly improved survival was achieved in mice treated with [211At]At-SPC-VP2, two-fold prolongation of survival compared with the control group, which received normal saline or 550 kBq [211At]NaAt. No renal or hepatic toxicity was observed in the mice receiving [211At]At-SPC-VP2, but gastric pathological sections showed 211At uptake in stomach resulting in later toxicity, highlighting the importance of further enhancing the stability of labelled compounds.

In vivo Experiments (Carassius gibelio Bloch) on Copper Homeostasis Alteration After Lead Intoxication and Natural Biologic-active Principles Treatments

2017 ◽  
Vol 68 (8) ◽  
pp. 1807-1810
Author(s):  
Marioara Nicula ◽  
Nicolae Pacala ◽  
Lavinia Stef ◽  
Ioan Pet ◽  
Tiberiu Iancu ◽  
...  
Keyword(s):  
Striated Muscle ◽  
Living Organism ◽  
Antagonistic Effect ◽  
Control Group ◽  
Fish Feed ◽  
High Concentration ◽  
Tissue Samples ◽  
In Vivo Experiments ◽  
Carassius Gibelio

Minerals are involved in the most metabolic pathways and are necessary for living organisms in different concentrations. When the concentration of these biominerals is unbalanced due to different factors, the metabolic processes are disturbed and the organism tries to find recovery solutions. Cu is one mineral indispensable for living organism, also for fishes, and its concentration it could be drastically reduced by the presence of high concentration of some heavy metals � like Pb, due to antagonistic effect. Our research evaluates the Pb toxic potential on Carassius gibelio Bloch on Cu distribution in different tissues and two natural solutions for potentiation of antagonistic effect of Pb on Cu. We worked on four different fish groups: control group (C); and for three experimental groups we add 75 ppm Pb � as Pb(NO3)2 x �H2O into the water from aquarium. To potent the Pb toxicity we add into the grounded fish feed 2% lyophilized garlic to E3 group and 2% chlorella to E4 group. Every group had 30 fishes in separate aquarium, the fishes were fed every 2 times a day and had 12h alternate light and dark. After 21 days of experiment the fishes were euthanized with cloves oil and the tissue samples were collected (brain, gill, gonads, intestine, kidney, liver, striated muscle � epaxial myotomes, cardiac muscle, and skin). The samples were analytical prepared for AAS in order to determinate the Cu concentration in all tissue samples. The results presented the best protection of garlic against antagonistic effect of Pb on Cu in brain and testicles, and the lowest protection in muscle-striatal; while chlorella best protection was observed in heart muscle, brain, kidney and liver, and lowest protection in muscle-striatal.

scholarly journals Acute Toxicity Study of Iron-21 Syrup in Female Wistar Rats

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 2637-2643
Author(s):  
Kirti G Sahu ◽  
Manish P Deshmukh ◽  
Sukeshini B Lote ◽  
Ashish B Budrani ◽  
Deepak S Khobragade
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
Oral Route ◽  
The Body ◽  
Control Group ◽  
Haematological Parameter ◽  
Oral Toxicity ◽  
Tissue Samples ◽  
Histopathological Studies

The iron-21 syrup is used for iron deficiency anaemia which supplies iron and calories a provide iron and calorie nutriment to recompense haemoglobin deprivation. The objective of this study is to determine acute oral toxicity of Iron-21 syrup in vivo in Wistar rats. Iron-21 Syrup formulation was given through the oral route. The syrup formulation was administered in three increasing doses of 3, 6 and 12 ml/kg body weight for concentration of 500, 1000 and 2000mg/kg respectively. The other group of rats designated as a control group was given the only vehicle orally. The test and control group contains five rats each. Tests, as well as control group rats, were sacrificed on the fifteenth day of treatment. The blood and tissue samples of test animals were sent for histopathological studies examination. Four parameters were observed throughout the study, and they are cage side observation, the effect to the body weight, haematological parameter and histopathology. All animals were survived till they sacrificed. No notable changes were found in behaviour, haematological and histopathology studies. The oral administration of Iron-21 Syrup is not shown any toxic effect in the animal at a given dose. Therefore, it is a safe remedy for human use.

Comparison of human cardiac gene expression profiles in paired samples of right atrium and left ventricle collected in vivo

2012 ◽  
Vol 44 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Julia Asp ◽  
Jane Synnergren ◽  
Marianne Jonsson ◽  
Göran Dellgren ◽  
Anders Jeppsson
Keyword(s):  
Gene Expression ◽  
Left Ventricle ◽  
Right Atrium ◽  
Expression Profiles ◽  
Artery Bypass ◽  
Global Gene Expression ◽  
Differentially Expressed ◽  
Tissue Samples ◽  
The Right

Studies of expressed genes in human heart provide insight into both physiological and pathophysiological mechanisms. This is of importance for extended understanding of cardiac function as well as development of new therapeutic drugs. Heart tissue for gene expression studies is generally hard to obtain, particularly from the ventricles. Since different parts of the heart have different functions, expression profiles should likely differ between these parts. The aim of the study was therefore to compare the global gene expression in cardiac tissue from the more accessible auricula of the right atrium to expression in tissue from the left ventricle. Tissue samples were collected from five men undergoing aortic valve replacement or coronary artery bypass grafting. Global gene expression analysis identified 542 genes as differentially expressed between the samples extracted from these two locations, corresponding to ∼2% of the genes covered by the microarray; 416 genes were identified as abundantly expressed in right atrium, and 126 genes were abundantly expressed in left ventricle. Further analysis of the differentially expressed genes according to available annotations, information from curated pathways and known protein interactions, showed that genes with higher expression in the ventricle were mainly associated with contractile work of the heart. Transcription in biopsies from the auricula of the right atrium on the other hand indicated a wider area of functions, including immunity and defense. In conclusion, our results suggest that biopsies from the auricula of the right atrium may be suitable for various genetic studies, but not studies directly related to muscle work.

Ultrastructural modification of cellular interactions in cancer tumor

1978 ◽  
Vol 36 (2) ◽  
pp. 318-319
Author(s):  
N. P. Dmitrieva
Keyword(s):  
Cancer Cells ◽  
Human Thyroid ◽  
Adjacent Cell ◽  
Main Role ◽  
Cellular Interactions ◽  
Electron Microscopic ◽  
Cancer Tumor ◽  
Normal Human ◽  
Characteristic Features

One of the most characteristic features of cancer cells is their ability to metastasia. It is suggested that the modifications of the structure and properties of cancer cells surfaces play the main role in this process. The present work was aimed at finding out what ultrastructural features apear in tumor in vivo which removal of individual cancer cells from the cell population can provide. For this purpose the cellular interactions in the normal human thyroid and cancer tumor of this gland electron microscopic were studied. The tissues were fixed in osmium tetroxide and were embedded in Araldite-Epon.In normal human thyroid the most common type of intercellular contacts was represented by simple junction formed by the parallelalignment of adjacent cell membranees leaving in between an intermembranes space 15-20 nm filled with electronlucid material (Fig. 1a). Sometimes in the basal part of cells dilatations of the intercellular space 40-50 nm wide were found (Fig. 1a). Here the cell surfaces may form single short microvilli.

Biomedical applications: Pitfalls in the practice

1994 ◽  
Vol 52 ◽  
pp. 378-379
Author(s):  
J. D. Shelburne ◽  
Peter Ingram ◽  
Victor L. Roggli ◽  
Ann LeFurgey
Keyword(s):  
Operating Room ◽  
Liquid Nitrogen ◽  
Lung Tissue ◽  
Biomedical Applications ◽  
Microprobe Analysis ◽  
Tissue Sample ◽  
Cellular Level ◽  
Tissue Samples ◽  
Asbestos Fibers

At present most medical microprobe analysis is conducted on insoluble particulates such as asbestos fibers in lung tissue. Cryotechniques are not necessary for this type of specimen. Insoluble particulates can be processed conventionally. Nevertheless, it is important to emphasize that conventional processing is unacceptable for specimens in which electrolyte distributions in tissues are sought. It is necessary to flash-freeze in order to preserve the integrity of electrolyte distributions at the subcellular and cellular level. Ideally, biopsies should be flash-frozen in the operating room rather than being frozen several minutes later in a histology laboratory. Electrolytes will move during such a long delay. While flammable cryogens such as propane obviously cannot be used in an operating room, liquid nitrogen-cooled slam-freezing devices or guns may be permitted, and are the best way to achieve an artifact-free, accurate tissue sample which truly reflects the in vivo state. Unfortunately, the importance of cryofixation is often not understood. Investigators bring tissue samples fixed in glutaraldehyde to a microprobe laboratory with a request for microprobe analysis for electrolytes.

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