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By selectively targeting a pathogenic mutation (TNNT2 p.R173W) in patient-specific iPSC-derived cardiac myocytes, we demonstrated that the knockout strategy ameliorates the dilated cardiomyopathy phenotype in vitro. Angiotensin-converting enzyme inhibitors are commonly used as cardioprotective agents and have recently been shown in clinical studies to be efficacious in the prevention of anthracycline-induced heart failure. https://doi.org/10.1007/10_2017_30 (2018). We aim to give readers a clear understanding of how molecular imaging can enable noninvasive tracking of cardiac gene transfer and expression. Moreover, patients in group (c) also benefited from PCI therapy: a decrease in cardiac perfusion abnormality, an increase in LVEF, and an improvement in quality of life. View details for DOI 10.1161/CIRCULATIONAHA.111.017954, View details for Web of Science ID 000294782800004, View details for PubMedCentralID PMC3181082. The prospect of changing the plasticity of terminally differentiated cells toward pluripotency has completely altered the outlook for biomedical research. Cardiac stem cell therapy remains hampered by acute donor cell death posttransplantation and the lack of reliable methods for tracking cell survival in vivo. The groups did not differ in age (5610 years in Group 1 vs. 577 years in Group 2, P=0.82), sex (male: 82% vs. 94%, P=0.40), LVEF (278% vs. 256%, P=0.18), or NT-proBNP (2350 pg/ml vs. 2831 pg/ml, P=0.32). In this study, hES cells were stably transduced with a double fusion reporter gene consisting of firefly luciferase and enhanced green fluorescent protein. There was a wide range of mean pulmonary arterial pressures (27-81 mm Hg) and RV end-diastolic volumes (111-576 mL), RVEFs (8%-67 %), and left ventricular ejection fractions (26%-72%) by MRI. Single cell transcriptional profiling reveals heterogeneity of human induced pluripotent stem cells. Currently, therapeutic genome editing in the cardiovascular field is centered on liver-targeting strategies to reduce cardiovascular risks. We examined the association between inflammatory, myocardial, and renal biomarkers and their role in ventricular recovery and outcome after TAVR.A total of 112 subjects undergoing TAVR were included in the prospective registry. Med. However, the use of quantitative dobutamine 99mTc-sestamibi SPECT imaging for enhanced detection of coronary stenosis has not been established. H9c2-Fluc cells (3x10(6)) were injected into thigh muscles of Sprague-Dawley rats (N=30) treated with cyclosporine, dexamethasone, mycophenolate mofetil, tacrolimus, or saline from day -3 to day +14. Nominal and ordinal logistic regression demonstrated that CTC counts could identify adenomas and CRC, including CRC stage.RESULTS: The CellMax test demonstrated a significant association between CTC counts and worsening disease status (Cuzick's P value < 0.0001) with respect to the adenoma-carcinoma sequence. Given their self-renewing and pluripotent capabilities, human embryonic stem cells (hESCs) are well poised as a cellular source for tissue regeneration therapy. Keeney, M., Ong, S., Padilla, A., Yao, Z., Goodman, S., Wu, J. C., Yang, F. Cortical bone-derived stem cells: a novel class of cells for myocardial protection. At the cellular level, miR-152 overexpression perturbed mitochondrial ultrastructure and dysregulated key genes involved in cardiomyocyte metabolism and inflammation. Xie, X., Chan, K. S., Cao, F., Huang, M., Li, Z., Lee, A., Weissman, I. L., Wu, J. C. Transplantation of Human Embryonic Stem Cell-Derived Endothelial Cells for Vascular Diseases, Trafficking Mesenchymal Stem Cell Engraftment and Differentiation in Tumor-Bearing Mice by Bioluminescence Imaging. Ozen, M. O., Sridhar, K., Ogut, M. G., Shanmugam, A., Avadhani, A. S., Kobayashi, Y., Wu, J. C., Haddad, F., Demirci, U. Pharmacological Silencing of MicroRNA-152 Prevents Pressure Overload-Induced Heart Failure. Molecular understanding of placental functions and pregnancy disorders is limited by the absence of methods for placenta-specific gene manipulation. This imaging technology also confirmed that ES cells indeed have immunogenic properties that factor into cell survival and differentiation. The hNSCs were genetically engineered with a lentiviral vector carrying a double fusion (DF) reporter gene that stably expressed enhanced green fluorescence protein (eGFP) and firefly luciferase (fLuc) reporter genes. Heart 98, 443449. (a) On day 3 of the differentiation protocol, cells were incubated with either WntC59 (2M) or Sfrp2 (1nM) for 2days. These two properties of ESCs and iPSCs make them potentially suitable for tissue engineering and cell replacement therapy for many different diseases, including Parkinson's disease, diabetes and heart disease. Despite some limitations, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a powerful and evolving technology that has been shown to recapitulate many attributes of human cardiomyocytes and their drug responses. View details for Web of Science ID 000298222000001, View details for DOI 10.1016/j.jcmg.2010.01.012, View details for Web of Science ID 000281626700015, View details for PubMedCentralID PMC2952324. Molecular imaging has proven to be a vital tool in the characterization of stem cell behavior in vivo. Karakikes, I., Stillitano, F., Nonnenmacher, M., Tzimas, C., Sanoudou, D., Termglinchan, V., Kong, C., Rushing, S., Hansen, J., Ceholski, D., Kolokathis, F., Kremastinos, D., Katoulis, A., Ren, L., Cohen, N., Gho, J. M., Tsiapras, D., Vink, A., Wu, J. C., Asselbergs, F. W., Li, R. A., Hulot, J., Kranias, E. G., Hajjar, R. J. View details for DOI 10.1096/fj.15-280982, View details for Web of Science ID 000372629100009. Human embryonic stem (hES) cells have a potential use for the repair and regeneration of injured tissues. 18F-FB-[Lys3]BBN had moderate stability in the blood and PC-3 tumor, whereas it was degraded rapidly in the liver, kidneys, and urine. Mice preinjected intravenously with unmodified Adtk resulted in high hepatic uptake and moderate tumor accumulation of the tracer. Cell therapy has recently made great strides towards aiding heart failure. Infarct-size measurements and BMC phenotype and function data were obtained for 101 patients (mean age, 56.5 years; mean screening ejection fraction, 37%; mean baseline cardiac MRI ejection fraction, 45%). Understanding the in vivo hESC behavior after transplantation requires novel imaging techniques to longitudinally monitor hESC localization, proliferation, and viability. The protein-level translational status and function of many alternative splicing events remain poorly understood. Cell Cardiol. Cells stimulated with a charged balanced voltage-controlled current source for up to 4 days were analyzed for cardiac and ES cell gene expression using real-time PCR, immunofluorescent imaging, and genome microarray analysis. A new class of composite materials has emerged to take advantage of the benefits of the strengths and minimize the weaknesses of both synthetic and natural materials. Hemodynamic forces regulate embryonic stem cell commitment to vascular progenitors. Characterization of cardiomyocytes derived from pluripotent cells often includes the analysis of reference markers, both at the mRNA and protein level. View details for DOI 10.1161/01.CIR.0000091252.20010.6E, View details for Web of Science ID 000185328800006. Mordwinkin, N. M., Gu, M., Kooreman, N. G., Hu, S., Churko, J. M., Diecke, S., Burridge, P. W., He, C., Lee, J., Gold, J. D., Wu, J. C. In Vivo Crosstalk Between Transplanted Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Host Myocardial Cells. Moneghetti, K. J., Giraldeau, G., Wheeler, M. T., Kobayashi, Y., Vrtovec, B., Boulate, D., Kuznetsova, T., Schnittger, I., Wu, J. C., Myers, J., Ashley, E., Haddad, F. Bioacoustic-enabled patterning of human iPSC-derived cardiomyocytes into 3D cardiac tissue. In both groups, CD34(+) cells were mobilized by filgrastim, collected via apheresis, and labeled with technetium-99m radioisotope for single-photon emission computed tomographic imaging. French, A., Bravery, C., Smith, J., Chandra, A., Archibald, P., Gold, J. D., Artzi, N., Kim, H., Barker, R. W., Meissner, A., Wu, J. C., Knowles, J. C., Williams, D., Garcia-Cardena, G., Sipp, D., Oh, S., Loring, J. F., Rao, M. S., Reeve, B., Wall, I., Carr, A. J., Bure, K., Stacey, G., Karp, J. M., Snyder, E. Y., Brindley, D. A. Longitudinal optical bioluminescence imaging was performed over two weeks. Regional myocardial flow was assessed at rest with radiolabeled microspheres. Hendry, S. L., van der Bogt, K. E., Sheikh, A. Y., Arai, T., Dylla, S. J., Drukker, M., McConnell, M. V., Kutschka, I., Hoyt, G., Cao, F., Weissman, I. L., Connolly, A. J., Pelletier, M. P., Wu, J. C., Robbins, R. C., Yang, P. C. Comparison of different adult stem cell types for treatment of myocardial ischemia. In this article, we manipulated Noggin expression levels in hASCs using lentiviral and nonintegrating minicircle short hairpin ribonucleic acid (shRNA) methodologies in vitro and in vivo to enhance hASC osteogenesis. Comparison between single hESCs and single hiPSCs revealed markedly more heterogeneity in gene expression levels in the hiPSCs, suggesting that hiPSCs occupy an alternate, less stable pluripotent state. View details for DOI 10.1146/annurev-genet-112414-054911, View details for DOI 10.1016/j.jacc.2015.08.664, View details for Web of Science ID 000363329000588. Importantly, E-PZ-iPS-like cells re-expressed basal epithelial cell markers (CD44, p63, MAO-A) in response to prostate-specific medium in spheroid culture. Our results demonstrate a novel application of Faraday waves to create stem cell-derived 3D cardiac tissue that resembles the cellular architecture of a native heart tissue for diverse basic research and clinical applications. American Journal of Nuclear Medicine and Molecular Imaging: Editorial Board (2014) e-Century Publishing Corporation. 161, 130138. View details for DOI 10.1634/stemcells.2007-0041, View details for Web of Science ID 000249929900031, View details for PubMedCentralID PMC3657503. Di Rocco, G., Gentile, A., Antonini, A., Ceradini, F., Wu, J. C., Capogrossi, M. C., Toietta, G. Launch of the american journal of nuclear medicine and molecular imaging. iPSc-derived cardiomyocytes were removed from the tissue culture plate with TrypsinEDTA (Thermo Fisher Scientific, 0.25%) and fixed in a solution containing 1% formaldehyde (Thermo Fisher Scientific) and 90% methanol (Sigma). Vero cells, or human-induced pluripotent stem cells (hiPSC)-derived cardiomyocytes (hiPSC-CM) were infected with T. cruzi trypomastigotes (discrete typing unit types I or II). Our results demonstrate short-lived survival of cells following transplant, with less than 1% of cells surviving by 6 weeks posttransplantation. Narsinh, K. H., Sun, N., Sanchez-Freire, V., Lee, A. S., Almeida, P., Hu, S., Jan, T., Wilson, K. D., Leong, D., Rosenberg, J., Yao, M., Robbins, R. C., Wu, J. C. Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells. View details for DOI 10.1016/j.nuclcard.2006.05.012, View details for Web of Science ID 000239736700014. Recent advances in the microRNA field and experimentally validated microRNAs warrant a review in experimental protocols for microRNA expression profile. Although the current drug safety screening methodologies can identify some cardiotoxic drug candidates, they cannot accurately represent the human heart in many aspects, including genomics, transcriptomics, and patient- or population-specific cardiotoxicity. Acquisition of echocardiographic data from rodents is subject to wide variability due to variations in technique. After two days incubation with the agents, the media was replaced with differentiation media from day 5 to day 9. Narsinh, K. H., Lan, F., Liu, J., Robbins, R. C., Wu, J. C. Development of Reporter Gene Techniques for Long-Term Assessment of Transplanted Human Circulating Progenitor Cells with Positron Emission Tomography. Using the custom databases to reanalyze 80 million mass spectra in public proteomics datasets, we identify more than 1,500 noncanonical protein isoforms across 12 human tissues, including 400 sequences undocumented on TrEMBL and RefSeq databases. View details for DOI 10.1161/01.CIR.0000138153.02213.22, View details for Web of Science ID 000223194700008, View details for DOI 10.1016/j.nuclcard.2004.04.004, View details for Web of Science ID 000223210200015. We established that ALDH2 controls cell survival decisions by modulating oxidative stress levels and that this regulatory circuitry was dysfunctional in the loss-of-function ALDH2*2 genotype, causing up-regulation of apoptosis in cardiomyocytes after ischemic insult. To assess sarcomere structure, cardiomyocytes were stained with an -Actinin (Actn2) antibody. Several allometric methods for indexing cardiac structures to body size have been proposed but the optimal way for normalization of cardiac structures is still controversial. Mitochondrial structure and CL content before and after incubation with the mitochondrially targeted peptide SS-31 were quantified.Patient iPSCs carry the causative DNAJC19 mutation (rs137854888) found in the Hutterite population, and the iPSC-CMs demonstrated highly fragmented and abnormally shaped mitochondria associated with an imbalanced isoform ratio of the mitochondrial protein OPA1, an important regulator of mitochondrial fusion. Pluripotent stem cells, both human embryonic stem cells (hESC) and human-induced pluripotent stem cells (hiPSC), can give rise to multiple cell types and hence have tremendous potential for regenerative therapies. Vismione B, therefore, might become a promising lead molecule for treatment development for CD. Cao, F., Xie, X., Gollan, T., Zhao, L., Narsinh, K., Lee, R. J., Wu, J. C. Timing of Bone Marrow Cell Delivery Has Minimal Effects on Cell Viability and Cardiac Recovery After Myocardial Infarction. Soma, Y. et al. Specifically, the cumulative upregulation of (1) a matrix metalloproteinase gene that has previously been implicated in plaque rupture, (2) potassium channel genes involved in membrane potential maintenance and action potential generation, and (3) sphingolipid and ceramide metabolism-related genes, together give cause for concern over rosiglitazone's safety. Minicircle (MC) DNA are supercoiled DNA molecules free of bacterial plasmid backbone elements and have been reported to enhance prolonged gene expression compared to conventional plasmids. Future studies will focus on improving this technology to allow for standardized high-throughput echocardiographic analysis in small animal models of disease. Therefore, it has been hypothesized that the shared antigens between tumors and embryonic/fetal tissues (oncofetal antigens) are the key to anti-tumor immune responses in these studies. Insights from molecular signature of in vivo cardiac c-Kit(+) cells following cardiac injury and beta-catenin inhibition. The use of hiPSCs is particularly valuable to the study of cardiac biology, as human cardiomyocytes are difficult to isolate and culture and have a limited proliferative potential. We further observe an increase in the expression of A(1-40) by flow cytometry and fluorescence microscopy. We report a new, straightforward and highly efficient approach for chondrogenic differentiation of hiPSCs, which avoids embryoid body formation. View details for DOI 10.1007/978-1-61779-145-1_7, View details for PubMedCentralID PMC3657515, View details for Web of Science ID 000208760300013, View details for PubMedCentralID PMC3477714, View details for PubMedCentralID PMC3477713. However, while transplanted cells may electromechanically integrate into host tissue, there may not be a uniform propagation of a depolarization wave between the heterogeneous tissue boundaries. Sprague-Dawley rats (n = 11) were imaged using high-resolution ultrasound, and stably transfected cardiomyoblasts (plasmid-CMV-firefly luciferase) were injected into the anterior cardiac wall under ultrasound guidance (parasternal long-axis view), using a 28-gauge needle. This advantage allows high throughput sequencing to be used to create large data sets, generating more comprehensive insights into the cellular genomic and transcriptomic signatures of various diseases and developmental stages. Finally, Western blot analysis confirmed significantly higher levels of HIF-1-alpha protein by MC-shPHD2, compared with PL-shPHD2 and PBS. We observed that VEGF-C is widely expressed in the outflow tract, while cardiomyocytes develop specifically within the aorta at stem sites where they surround maturing CAs in both mouse and human hearts. In a prophylactic setting, iPSC vaccines prevent tumor growth in syngeneic murine breast cancer, mesothelioma, and melanoma models. Recently, approaches for generating cardiomyocytes have expanded to encompass three major sources of starting cells: human pluripotent stem cells (hPSCs), adult heart-derived cardiac progenitor cells (CPCs), and reprogrammed fibroblasts. Proposed mechanism of Sfrp2 action. Molecular imaging has given investigators a high-throughput, inexpensive, and sensitive means for tracking in vivo cell proliferation over days, weeks, and even months. N=3. These ES-derived CD31(+) cells express endothelial nitric oxide synthase (eNOS) and von Willebrand factor (vWF). Human induced pluripotent stem cells (hiPSCs) generated by de-differentiation of adult somatic cells offer potential solutions for the ethical issues surrounding human embryonic stem cells (hESCs), as well as their immunologic rejection after cellular transplantation. View details for DOI 10.1097/TP.0b013e31819609d9. The specificity of our custom-designed 7-repeat STAT3 reporter construct was first confirmed by cotransfection with constitutively active version of STAT3 (STAT3C) into human embryonic kidney 293T cells. The therapeutic potential of iPSCs makes it important to understand the reprogramming mechanisms and iPSC differentiation process. Results present an efficient and clinically translatable approach for cartilage tissue regeneration via patient-derived hiPSCs, which could improve cartilage regeneration outcomes in arthritic joints. Early SB216763 therapy prevented heart failure and reduced mortality in the fish model. Recently, we have demonstrated that mature cardiomyogenesis is induced in vivo by Secreted Frizzled Related Protein 2 (Sfrp2)12,13. Our data indicate that vismione B is more potent against T. cruzi infection and multiplication than BNZ, with stronger effects on established infection. Patient-specific iPSC-derived cardiomyocytes offer an attractive experimental platform to model cardiovascular diseases, study the earliest stages of human development, accelerate predictive drug toxicology tests, and advance potential regenerative therapies. A., Wang, Q., Paulmurugan, R., Rosenberg, J., Rodriguez-Porcel, M., Willmann, J. K., Wang, D. S., Contag, C. H., Robbins, R. C., Wu, J. C., Gambhir, S. S. CD34(+) Stem Cell Therapy in Nonischemic Dilated Cardiomyopathy Patients. Intramyocardial delivery of pcTnT-HIF-1-VP2-TSTA-fluc into infarcted mouse myocardium led to persistent HIF-1-VP2 expression for 4 weeks, even though it improved neither CD31+ microvessel density nor echocardiographically determined left ventricular systolic function. This review discusses the utility of nonclinical models (in vitro, in vivo,&in silico) available and highlights recent advancements in modalities like human stem cell-derived cardiomyocytes for developing more comprehensive cardiotoxicity testing and new means of cardioprotection with targeted anticancer therapies. (Maywood.) We have developed a bidirectional plasmid vector, which uses a two-step transcriptional amplification (TSTA) strategy to enhance the expression of two optical reporter genes, firefly luciferase (fluc) and Renilla luciferase (hrluc), driven by the cardiac troponin T (cTnT) promoter. Next, we created MC carrying HIF-1alpha (MC-HIF-1alpha) therapeutic gene for treatment of myocardial infarction. View details for DOI 10.1371/journal.pone.0134995. Fluorescence-activated cell sorting (FACS) analysis isolated stably transduced populations. Stem. We hope these topics are of interest to our readers. Unexpected toxicity can occur during treatment and/or after completion of therapy, into the time of cancer survivorship. View details for DOI 10.1161/CIRCGENETICS.109.934281, View details for Web of Science ID 000283163100006, View details for PubMedCentralID PMC3057038. Among these cytokines, after adjustment for confounders, interleukin 18 remained significantly different between HTN participants with and without LV involvement (P=.02). Z., Patel, M., Wu, J. C., Gambhir, S. S., Chen, X. Y. OBJECTIVES: There is a significant unmet need for a blood test with adequate sensitivity to detect colorectal cancer (CRC) and adenomas. We report a 23-year-old male with history of double-inlet single ventricle with transposition of the great arteries who is s/p pulmonary artery banding, a Damus-Kaye-Stanzel anastomosis, and Fontan procedure during infancy and childhood who now presents with chest pain. These results provide a promising tool for imaging stem cell therapy non-invasively in vivo. In addition, iPSC-CMs have shown some features of the respective phenotypes for arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), LEOPARD syndrome, Pompe's disease, and Friedriech's ataxia. On-line visualization of ischemic burden during repetitive ischemia/reperfusion. Lijkwan, M. A., Hellingman, A. With the advent of induced pluripotent stem cell (iPSC) technology, patient-specific stem cells can be developed and expanded into an indefinite source of cells. https://doi.org/10.1016/j.yjmcc.2021.04.006 (2021). Published online 2015 Mar 18. doi: 10.3791/52628 PMCID: PMC4401368 NIHMSID: NIHMS821956 PMID: 25867738 Derivation of Highly Purified Cardiomyocytes from Human Induced Pluripotent Stem Cells Using Small Molecule-modulated Differentiation and Subsequent Glucose Starvation Deuse, T., Peter, C., Fedak, P. W., Doyle, T., Reichenspurner, H., Zimmermann, W. H., Eschenhagen, T., Stein, W., Wu, J. C., Robbins, R. C., Schrepfer, S. nAChRs Mediate Human Embryonic Stem Cell-Derived Endothelial Cells: Proliferation, Apoptosis, and Angiogenesis. Pluripotent embryonic stem can (ES) cells can differentiate into all cell lineages. We determined that optical molecular imaging expedites the fast throughput screening of pharmaceutical agents, allowing for the noninvasive tracking of cell survival within animals. Importantly, reducing PDK4 levels restored mitochondrial metabolism, reduced cell proliferation, and improved endothelial-pericyte interactions. Bioluminescence reporter gene imaging of human embryonic stem cell survival, proliferation, and fate. Teratoma formation is a critical obstacle to safe clinical translation of human embryonic stem (ES) cell-based therapies in the future. STAT3 acts as a key transcriptional determinant of mouse embryonic stem (ES) cell self-renewal and plays a pivotal function in early mammalian embryogenesis because the development of many organs requires STAT3 activation.

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