WorldWideScience

Sample records for heart cell therapies

  1. Challenges for heart disease stem cell therapy

    Directory of Open Access Journals (Sweden)

    Hoover-Plow J

    2012-02-01

    Full Text Available Jane Hoover-Plow, Yanqing GongDepartments of Cardiovascular Medicine and Molecular Cardiology, Joseph J Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USAAbstract: Cardiovascular diseases (CVDs are the leading cause of death worldwide. The use of stem cells to improve recovery of the injured heart after myocardial infarction (MI is an important emerging therapeutic strategy. However, recent reviews of clinical trials of stem cell therapy for MI and ischemic heart disease recovery report that less than half of the trials found only small improvements in cardiac function. In clinical trials, bone marrow, peripheral blood, or umbilical cord blood cells were used as the source of stem cells delivered by intracoronary infusion. Some trials administered only a stem cell mobilizing agent that recruits endogenous sources of stem cells. Important challenges to improve the effectiveness of stem cell therapy for CVD include: (1 improved identification, recruitment, and expansion of autologous stem cells; (2 identification of mobilizing and homing agents that increase recruitment; and (3 development of strategies to improve stem cell survival and engraftment of both endogenous and exogenous sources of stem cells. This review is an overview of stem cell therapy for CVD and discusses the challenges these three areas present for maximum optimization of the efficacy of stem cell therapy for heart disease, and new strategies in progress.Keywords: mobilization, expansion, homing, survival, engraftment

  2. Stem cell therapy to treat heart ischaemia

    DEFF Research Database (Denmark)

    Ali Qayyum, Abbas; Mathiasen, Anders Bruun; Kastrup, Jens

    2014-01-01

    (CABG), morbidity and mortality is still high in patients with CAD. Along with PCI and CABG or in patients without options for revascularization, stem cell regenerative therapy in controlled trials is a possibility. Stem cells are believed to exert their actions by angiogenesis and regeneration...... of cardiomyocytes. Recently published clinical trials and meta-analysis of stem cell studies have shown encouraging results with increased left ventricle ejection fraction and reduced symptoms in patients with CAD and heart failure. There is some evidence of mesenchymal stem cell being more effective compared...... to other cell types and cell therapy may be more effective in patients with known diabetes mellitus. However, further investigations are warranted....

  3. Adult stem cell therapy for the heart.

    Science.gov (United States)

    Fraser, John K; Schreiber, Ronda E; Zuk, Patricia A; Hedrick, Marc H

    2004-04-01

    The purpose of this review is to summarize current data leading to and arising from recent clinical application of cellular therapy for acute myocardial infarct (heart attack) and congestive heart failure. We specifically focus on use of adult stem cells and compare and contrast bone marrow and adipose tissue; two different sources from which stem cells can be harvested in substantial numbers with limited morbidity. Cellular therapy is the latest in a series of strategies applied in an effort to prevent or mitigate the progressive and otherwise irreversible loss of cardiac function that frequently follows a heart attack. Unlike surgical, pharmacologic, and gene transfer approaches, cellular therapy has the potential to restore cardiac function by providing cells capable of regenerating damaged myocardium and/or myocardial function. Skeletal muscle myoblast expansion and transfer allows delivery of cells with contractile function, albeit without any evidence of cardiomyogenesis or electrical coupling to remaining healthy myocardium. Delivery of endothelial progenitor cells (EPCs) which drive reperfusion of infarct zone tissues is also promising, although this mechanism is directed at halting ongoing degeneration rather than initiating a regenerative process. By contrast, demonstration of the ability of adult stem cells to undergo cardiomyocyte differentiation both in vitro and in vivo suggests a potential for regenerative medicine. This potential is being examined in early clinical studies.

  4. Stem Cell Therapy for Congestive Heart Failure

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    Gunduz E

    2011-01-01

    Full Text Available IntroductionHeart failure is a major cardiovascular health problem. Coronary artery disease is the leading cause of congestive heart failure (CHF [1]. Cardiac transplantation remains the most effective long-term treatment option, however is limited primarily by donor availability, rejection and infections. Mechanical circulatory support has its own indications and limitations [2]. Therefore, there is a need to develop more effective therapeutic strategies.Recently, regenerative medicine has received considerable scientific attention in the cardiovascular arena. We report here our experience demonstrating the beneficial effects of cardiac stem cell therapy on left ventricular functions in a patient with Hodgkin’s lymphoma (HL who developed CHF due to ischemic heart disease during the course of lymphoma treatment. Case reportA 58-year-old male with relapsed HL was referred to our bone marrow transplantation unit in October 2009. He was given 8 courses of combination chemotherapy with doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD between June 2008 and February 2009 and achieved complete remission. However, his disease relapsed 3 months after completing the last cycle of ABVD and he was decided to be treated with DHAP (cisplatin, cytarabine, dexamethasone followed autologous stem cell transplantation (SCT. After the completion of first course of DHAP regimen, he developed acute myocardial infarction (AMI and coronary artery bypass grafting (CABG was performed. After his cardiac function stabilized, 3 additional courses of DHAP were given and he was referred to our centre for consideration of autologous SCT. Computed tomography scans obtained after chemotherapy confirmed complete remission. Stem cells were collected from peripheral blood after mobilization with 10 µg/kg/day granulocyte colony-stimulating factor (G-CSF subcutaneously. Collection was started on the fifth day of G-CSF and performed for 3 consecutive days. Flow cytometric

  5. Perspective in optimization of stem cell therapies for heart regeneration.

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    Gapska, Paulina; Kurpisz, Maciej

    2017-12-07

    There is a variety of mechanisms(s) factor(s) that may influence stem cell therapies for heart regeneration. Among the best candidates for stem cell source are: mesenchymal stem cells (also those isolated from adipose tissue), cardiac cell progenitors (CPC) and descendants of iPSC cells. iPSC/s can be potentially beneficial although their pluripotent induction has been still in question due to: low propagation efficacy, danger of genomic integration/instability, biological risk of current vector system teratoma formation etc. which have been discussed in this review. Optimization protocols are required in order to enhance stem cells resistance to pathological conditions that they may encounter in pathological organ and to increase their retention. Combination between gene transfer and stem cell therapy is now more often used in pre-clinical studies with the prospect of subsequent clinical trials. Complementary substances have been contemplated to support stem cell viability (mainly anti-inflammatory and anti- apoptotic agents), which have been tested in animal models with promising results. Integration of nanotechnology both for efficient stem cell imaging as well as with the aim to provide cell supporting scaffolds seem to be inevitable for further development of cellular therapies. The whole organ (heart) reconstruction as well as biodegradable scaffolds and scaffold-free cell sheets have been also outlined.

  6. Perspective in optimization of stem cell therapies for heart regeneration

    Directory of Open Access Journals (Sweden)

    Paulina Gapska

    2017-12-01

    Full Text Available There is a variety of mechanisms(s factor(s that may influence stem cell therapies for heart regeneration. Among the best candidates for stem cell source are: mesenchymal stem cells (also those isolated from adipose tissue, cardiac cell progenitors (CPC and descendants of iPSC cells. iPSC/s can be potentially beneficial although their pluripotent induction has been still in question due to: low propagation efficacy, danger of genomic integration/instability, biological risk of current vector system teratoma formation etc. which have been discussed in this review. Optimization protocols are required in order to enhance stem cells resistance to pathological conditions that they may encounter in pathological organ and to increase their retention. Combination between gene transfer and stem cell therapy is now more often used in pre-clinical studies with the prospect of subsequent clinical trials. Complementary substances have been contemplated to support stem cell viability (mainly anti-inflammatory and anti- apoptotic agents, which have been tested in animal models with promising results. Integration of nanotechnology both for efficient stem cell imaging as well as with the aim to provide cell supporting scaffolds seem to be inevitable for further development of cellular therapies. The whole organ (heart reconstruction as well as biodegradable scaffolds and scaffold-free cell sheets have been also outlined.

  7. Stem Cell Therapy for Congenital Heart Disease: A Systematic Review.

    Science.gov (United States)

    Tsilimigras, Diamantis I; Oikonomou, Evangelos K; Moris, Demetrios; Schizas, Dimitrios; Economopoulos, Konstantinos P; Mylonas, Konstantinos S

    2017-12-12

    Congenital heart disease (CHD) constitutes the most prevalent and heterogeneous group of congenital anomalies. Although surgery remains the gold standard treatment modality, stem cell therapy has been gaining ground as a complimentary or alternative treatment option in certain types of CHD. The aim of this study was to present the existing published evidence and ongoing research efforts on the implementation of stem cell-based therapeutic strategies in CHD. A systematic review was conducted by searching Medline, ClinicalTrials.gov, and the Cochrane library, along with reference lists of the included studies through April 23, 2017. Nineteen studies were included in this review (8 preclinical, 6 clinical, and 5 ongoing trials). Various routes of cardiac stem cell delivery have been reported, including intracoronary, intramyocardial, intravenous, and epicardial. Depending on their origin and level of differentiation at which they are harvested, stem cells may exhibit different properties. Preclinical studies have mostly focused on modeling right ventricle dysfunction or failure and pulmonary artery hypertension by using pressure or volume overload in vitro or in vivo. Only a limited number of clinical trials on patients with CHD exist, and these primarily focus on hypoplastic left heart syndrome. Cell-based tissue engineering has recently been introduced, and research currently is focusing on developing cell-seeded grafts and patches that could potentially grow in parallel with whole body growth once implanted in the heart. It seems that stem cell delivery to the diseased heart as an adjunct to surgical palliation may provide some benefits over surgery alone in terms of cardiac function, somatic growth, and quality of life. Despite encouraging preliminary results, stem cell therapies for patients with CHD should only be considered in the setting of well-designed clinical trials. More wet laboratory research experience is needed, and translation of promising findings

  8. Stem cell therapy and tissue engineering for correction of congenital heart disease

    OpenAIRE

    Avolio, Elisa; Caputo, Massimo; Madeddu, Paolo

    2015-01-01

    This review article reports on the new field of stem cell therapy and tissue engineering and its potential on the management of congenital heart disease. To date, stem cell therapy has mainly focused on treatment of ischemic heart disease and heart failure, with initial indication of safety and mild-to-moderate efficacy. Preclinical studies and initial clinical trials suggest that the approach could be uniquely suited for the correction of congenital defects of the heart. The basic concept is...

  9. Stem cell therapy and tissue engineering for correction of congenital heart disease

    Science.gov (United States)

    Avolio, Elisa; Caputo, Massimo; Madeddu, Paolo

    2015-01-01

    This review article reports on the new field of stem cell therapy and tissue engineering and its potential on the management of congenital heart disease. To date, stem cell therapy has mainly focused on treatment of ischemic heart disease and heart failure, with initial indication of safety and mild-to-moderate efficacy. Preclinical studies and initial clinical trials suggest that the approach could be uniquely suited for the correction of congenital defects of the heart. The basic concept is to create living material made by cellularized grafts that, once implanted into the heart, grows and remodels in parallel with the recipient organ. This would make a substantial improvement in current clinical management, which often requires repeated surgical corrections for failure of implanted grafts. Different types of stem cells have been considered and the identification of specific cardiac stem cells within the heterogeneous population of mesenchymal and stromal cells offers opportunities for de novo cardiomyogenesis. In addition, endothelial cells and vascular progenitors, including cells with pericyte characteristics, may be necessary to generate efficiently perfused grafts. The implementation of current surgical grafts by stem cell engineering could address the unmet clinical needs of patients with congenital heart defects. PMID:26176009

  10. Stem cell therapy and tissue engineering for correction of congenital heart disease

    Directory of Open Access Journals (Sweden)

    Elisa eAvolio

    2015-06-01

    Full Text Available This review article reports on the new field of stem cell therapy and tissue engineering and its potential on the management of congenital heart disease. To date, stem cell therapy has mainly focused on treatment of ischemic heart disease and heart failure, with initial indication of safety and mild-to-moderate efficacy. Preclinical studies and initial clinical trials suggest that the approach could be uniquely suited for the correction of congenital defects of the heart. The basic concept is to create living material made by cellularized grafts that, once implanted into the heart, grows and remodels in parallel with the recipient organ. This would make a substantial improvement in current clinical management, which often requires repeated surgical corrections for failure of implanted grafts. Different types of stem cells have been considered and the identification of specific cardiac stem cells within the heterogeneous population of mesenchymal and stromal cells offers opportunities for de novo cardiomyogenesis. In addition, endothelial cells and vascular progenitors, including cells with pericyte characteristics, may be necessary to generate efficiently perfused grafts. The implementation of current surgical grafts by stem cell engineering could address the unmet clinical needs of patients with congenital heart defects.

  11. Stem cell therapy and tissue engineering for correction of congenital heart disease.

    Science.gov (United States)

    Avolio, Elisa; Caputo, Massimo; Madeddu, Paolo

    2015-01-01

    This review article reports on the new field of stem cell therapy and tissue engineering and its potential on the management of congenital heart disease. To date, stem cell therapy has mainly focused on treatment of ischemic heart disease and heart failure, with initial indication of safety and mild-to-moderate efficacy. Preclinical studies and initial clinical trials suggest that the approach could be uniquely suited for the correction of congenital defects of the heart. The basic concept is to create living material made by cellularized grafts that, once implanted into the heart, grows and remodels in parallel with the recipient organ. This would make a substantial improvement in current clinical management, which often requires repeated surgical corrections for failure of implanted grafts. Different types of stem cells have been considered and the identification of specific cardiac stem cells within the heterogeneous population of mesenchymal and stromal cells offers opportunities for de novo cardiomyogenesis. In addition, endothelial cells and vascular progenitors, including cells with pericyte characteristics, may be necessary to generate efficiently perfused grafts. The implementation of current surgical grafts by stem cell engineering could address the unmet clinical needs of patients with congenital heart defects.

  12. Mesenchymal stromal cell therapy in ischemic heart disease

    DEFF Research Database (Denmark)

    Kastrup, Jens; Mygind, Naja Dam; Ali Qayyum, Abbas

    2016-01-01

    Although, treatment of ischemic heart disease (IHD) has improved considerably within the last decades, it is still the main cause of death worldwide. Despite maximum treatment, many IHD patients suffer from refractory angina and heart failure, which severely limits their daily lives. Moreover, IHD...

  13. Stem cell therapy for end-stage heart failure : indispensable role for the cell?

    NARCIS (Netherlands)

    Vrijsen, K. R.; Chamuleau, S. A. J.; Noort, W. A.; Doevendans, P. A.; Sluijter, J. P. G.

    2009-01-01

    Purpose of review For heart failure patients, the urgent need for heart transplantation exceeds the availability of donor hearts. Therefore, cell transplantation has emerged as an interesting and potential solution. This review will focus on the capability of different types of stem cells to

  14. Stem cell therapy for ischemic heart disease: beginning or end of the road?

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    Stamm, Christof; Liebold, Andreas; Steinhoff, Gustav; Strunk, Dirk

    2006-01-01

    Despite improvements in emergency treatment, myocardial infarction is often the beginning of a downward spiral leading to congestive heart failure. Other than heart transplantation, current therapeutic means aim at enabling the organism to survive with a heart that is working at a fraction of its original capacity. It is therefore no surprise that cardiac stem cell therapy has raised many hopes. However, neither the ideal source and type of stem cell nor the critical cell number and mode of application have been defined so far. Early reports on myocardial repair by adult bone marrow stem cells from rodent models promoted an unparalleled boost of clinical and experimental cell therapy studies. The phenomenon of stem/progenitor cell-induced angiogenesis in ischemic myocardium has ever since been reproduced by numerous groups in a variety of small and large animal models. Myogenesis, however, is an altogether different matter. Many of the initial clinical studies were fueled by the suggestion that early hematopoietic stem cells have a plasticity high enough to enable cross-lineage differentiation into cells of cardiomyocyte phenotype, but the initial enthusiasm has largely faded. The myogenic potential of stroma cell-derived mesenchymal stem cells is much better documented in animal models, but transfer to the clinical setting faces a variety of obstacles. In clinical pilot trials, we and others have demonstrated the feasibility and safety of administering progenitor cells derived from autologous bone marrow to the myocardium of patients with ischemic heart disease. Clinical efficacy data are still rare, but the few controlled trials that have been completed uniformly show a tendency towards better heart function in cell-treated patients. This review is an attempt to describe the scientific basis for cardiac cell therapy from the point of view of the clinician, focusing on problems that arise with beginning translation into the clinical setting.

  15. Comment on: "Cell Therapy for Heart Disease: Trial Sequential Analyses of Two Cochrane Reviews"

    DEFF Research Database (Denmark)

    Castellini, Greta; Nielsen, Emil Eik; Gluud, Christian

    2017-01-01

    Trial Sequential Analysis is a frequentist method to help researchers control the risks of random errors in meta-analyses (1). Fisher and colleagues used Trial Sequential Analysis on cell therapy for heart diseases (2). The present article discusses the usefulness of Trial Sequential Analysis...

  16. Development of a Multifunctional Needle for Percutaneous Heart Biopsy and Cell Therapy. A Technical Note.

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    Soubihe, Nathan Valle; Albuquerque, Agnes Afrodite S; Arcêncio, Livia; Thomazini, José Antonio; Schmidt, Andre; Evora, Paulo Roberto B

    2016-01-01

    Validation of transendocardial injection as a method for delivering therapeutic agents to the diseased heart is increasing. Puncture heart biopsies should re-emerge as a possible alternative method to allow access to the myocardium and implantable biomaterial for cell therapy. Therefore, this work aims to present a percutaneous puncture device for biopsy and intramyocardial biomaterial injection, standardize the technique and attest to the safety of the method. The adaptation consists of creating myocardial microlesions that allow for better fixation of stem cells. The objective of this technical note covers only the development of the needle and the histological quality of the biopsies. It has not been used in humans yet.

  17. Multicenter randomized trial of cell therapy in cardiopathies – MiHeart Study

    Directory of Open Access Journals (Sweden)

    Oliveira Sérgio A

    2007-01-01

    Full Text Available Abstract Background Cardiovascular diseases are the major cause of death in the world. Current treatments have not been able to reverse this scenario, creating the need for the development of new therapies. Cell therapies have emerged as an alternative for cardiac diseases of distinct causes in experimental animal studies and more recently in clinical trials. Method/Design We have designed clinical trials to test for the efficacy of autologous bone marrow derived mononuclear cell therapies in four different cardiopathies: acute and chronic ischemic heart disease, and Chagasic and dilated cardiomyopathy. All trials are multicenter, randomized, double-blind and placebo controlled. In each trial 300 patients will be enrolled and receive optimized therapy for their specific condition. Additionally, half of the patients will receive the autologous bone marrow cells while the other half will receive placebo (saline with 5% autologous serum. For each trial there are specific inclusion and exclusion criteria and the method for cell delivery is intramyocardial for the chronic ischemic heart disease and intracoronary for all others. Primary endpoint for all studies will be the difference in ejection fraction (determined by Simpson's rule six and twelve months after intervention in relation to the basal ejection fraction. The main hypothesis of this study is that the patients who receive the autologous bone-marrow stem cell implant will have after a 6 month follow-up a mean increase of 5% in absolute left ventricular ejection fraction in comparison with the control group. Discussion Many phase I clinical trials using cell therapy for cardiac diseases have already been performed. The few randomized studies have yielded conflicting results, rendering necessary larger well controlled trials to test for efficacy of cell therapies in cardiopathies. The trials registration numbers at the NIH registry are the following: Chagasic cardiomyopathy (NCT00349271

  18. Materializing Heart Regeneration: Biomimicry of Key Observations in Cell Transplantation Therapies and Natural Cardiac Regeneration

    Science.gov (United States)

    Kong, Yen P.; Jongpaiboonkit, Leena

    2016-07-01

    New regenerative paradigms are needed to address the growing global problem of heart failure as existing interventions are unsatisfactory. Outcomes from the current paradigm of cell transplantation have not been stellar but the mechanistic knowledge learned from them is instructive in the development of future paradigms. An emerging biomaterial-based approach incorporating key mechanisms and additional ones scrutinized from the process of natural heart regeneration in zebrafish may become the next evolution in cardiac repair. We highlight, with examples, tested key concepts and pivotal ones that may be integrated into a successful therapy.

  19. Mechanistic molecular imaging of cardiac cell therapy for ischemic heart disease.

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    Yu, Qiujun; Fan, Weiwei; Cao, Feng

    2013-10-01

    Cell-based myocardial regeneration has emerged as a promising therapeutic option for ischemic heart disease, though not yet at the level of routine clinical utility. Despite the encouraging results from initial preclinical studies that have demonstrated improved function and reduced infarct size of the ischemic myocardium following several candidate cell transplantation, the beneficial effects and molecular mechanisms of cardiac cell therapy are still unclear in clinical applications to date, and much remains to be optimized. To improve engraftment, accurate methods are required for tracking cell fate and quantifying functional outcome. In the present review, we summarized the current status and challenges of cardiac cell therapy for ischemic heart disease and discussed the strengths and limitations of currently available in vivo imaging techniques with special focus on the newly developed multimodality approaches for assessing the efficacy of engrafted donor cells. We also addressed the hurdles these imaging modalities are facing, including issues regarding immunogenicity and tumorigenicity of transplanted stem cells, and provided some the future perspectives on stem cell imaging.

  20. Development of a Multifunctional Needle for Percutaneous Heart Biopsy and Cell Therapy. A Technical Note

    Directory of Open Access Journals (Sweden)

    Nathan Valle Soubihe Junior

    Full Text Available Abstract Validation of transendocardial injection as a method for delivering therapeutic agents to the diseased heart is increasing. Puncture heart biopsies should re-emerge as a possible alternative method to allow access to the myocardium and implantable biomaterial for cell therapy. Therefore, this work aims to present a percutaneous puncture device for biopsy and intramyocardial biomaterial injection, standardize the technique and attest to the safety of the method. The adaptation consists of creating myocardial microlesions that allow for better fixation of stem cells. The objective of this technical note covers only the development of the needle and the histological quality of the biopsies. It has not been used in humans yet.

  1. Cell-sheet therapy with omentopexy promotes arteriogenesis and improves coronary circulation physiology in failing heart.

    Science.gov (United States)

    Kainuma, Satoshi; Miyagawa, Shigeru; Fukushima, Satsuki; Pearson, James; Chen, Yi Ching; Saito, Atsuhiro; Harada, Akima; Shiozaki, Motoko; Iseoka, Hiroko; Watabe, Tadashi; Watabe, Hiroshi; Horitsugi, Genki; Ishibashi, Mana; Ikeda, Hayato; Tsuchimochi, Hirotsugu; Sonobe, Takashi; Fujii, Yutaka; Naito, Hisamichi; Umetani, Keiji; Shimizu, Tatsuya; Okano, Teruo; Kobayashi, Eiji; Daimon, Takashi; Ueno, Takayoshi; Kuratani, Toru; Toda, Koichi; Takakura, Nobuyuki; Hatazawa, Jun; Shirai, Mikiyasu; Sawa, Yoshiki

    2015-02-01

    Cell-sheet transplantation induces angiogenesis for chronic myocardial infarction (MI), though insufficient capillary maturation and paucity of arteriogenesis may limit its therapeutic effects. Omentum has been used clinically to promote revascularization and healing of ischemic tissues. We hypothesized that cell-sheet transplantation covered with an omentum-flap would effectively establish mature blood vessels and improve coronary microcirculation physiology, enhancing the therapeutic effects of cell-sheet therapy. Rats were divided into four groups after coronary ligation; skeletal myoblast cell-sheet plus omentum-flap (combined), cell-sheet only, omentum-flap only, and sham operation. At 4 weeks after the treatment, the combined group showed attenuated cardiac hypertrophy and fibrosis, and a greater amount of functionally (CD31(+)/lectin(+)) and structurally (CD31(+)/α-SMA(+)) mature blood vessels, along with myocardial upregulation of relevant genes. Synchrotron-based microangiography revealed that the combined procedure increased vascularization in resistance arterial vessels with better dilatory responses to endothelium-dependent agents. Serial (13)N-ammonia PET showed better global coronary flow reserve in the combined group, mainly attributed to improvement in the basal left ventricle. Consequently, the combined group had sustained improvements in cardiac function parameters and better functional capacity. Cell-sheet transplantation with an omentum-flap better promoted arteriogenesis and improved coronary microcirculation physiology in ischemic myocardium, leading to potent functional recovery in the failing heart.

  2. Lung and Heart Dose Variability During Radiation Therapy of Non-Small Cell Lung Cancer.

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    Jan, Nuzhat; Guy, Christopher; Reshko, Leonid B; Hugo, Geoffrey D; Weiss, Elisabeth

    2017-07-01

    To investigate the hypothesis that positional and anatomic variations during radiation therapy induce changes in lung and heart volumes and associated radiation doses. In this longitudinal investigation, variations in lung and heart volumes and standard dose parameters of mean lung dose, lung V20Gy, mean heart dose, and heart V40Gy were analyzed on weekly 4-dimensional CT scans of 15 lung cancer patients during conventionally fractionated radiochemotherapy. Tumor, individual lung lobes, and heart were delineated on the mid-ventilation phase of weekly 4-dimensional CT scans. Lung lobes and heart were also contoured on individual breathing phases of pre-, mid-, and end-of-treatment scans. Planning dose was transferred to consecutive scans via rigid registration. Volume and dose variations were assessed relative to the initial planning scan. Interfraction lung volume variability relative to week 0 was twice as large as tidal volume variability (8.0% ± 5.3% vs 4.0% ± 3.3%, P=.003). Interfraction lung volume variation ranged between 0.8% and 17.1% for individual patient means. Lower lung lobes had larger volume variability compared with upper lobes (13.5% ± 8.1% vs 7.0% ± 5.0%, Pheart volume variation was 7.2% (range, 3.4%-12.6%). Average mean heart dose variation was 1.2 Gy (range, 0.1-3.0 Gy) and average heart V40Gy variation 1.4% (range, 0%-4.2%). Anatomic and positional variations during radiation therapy induce changes in radiation doses to lung and heart. Repeated lung and heart dose assessment will provide a better estimate of the actual delivered dose and will improve prediction models for normal tissue toxicity, if assessed in larger cohorts. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Cellular Therapy for Heart Failure

    Science.gov (United States)

    Psaltis, Peter J.; Schwarz, Nisha; Toledo-Flores, Deborah; Nicholls, Stephen J.

    2016-01-01

    The pathogenesis of cardiomyopathy and heart failure (HF) is underpinned by complex changes at subcellular, cellular and extracellular levels in the ventricular myocardium. For all of the gains that conventional treatments for HF have brought to mortality and morbidity, they do not adequately address the loss of cardiomyocyte numbers in the remodeling ventricle. Originally conceived to address this problem, cellular transplantation for HF has already gone through several stages of evolution over the past two decades. Various cell types and delivery routes have been implemented to positive effect in preclinical models of ischemic and nonischemic cardiomyopathy, with pleiotropic benefits observed in terms of myocardial remodeling, systolic and diastolic performance, perfusion, fibrosis, inflammation, metabolism and electrophysiology. To a large extent, these salubrious effects are now attributed to the indirect, paracrine capacity of transplanted stem cells to facilitate endogenous cardiac repair processes. Promising results have also followed in early phase human studies, although these have been relatively modest and somewhat inconsistent. This review details the preclinical and clinical evidence currently available regarding the use of pluripotent stem cells and adult-derived progenitor cells for cardiomyopathy and HF. It outlines the important lessons that have been learned to this point in time, and balances the promise of this exciting field against the key challenges and questions that still need to be addressed at all levels of research, to ensure that cell therapy realizes its full potential by adding to the armamentarium of HF management. PMID:27280304

  4. Rationale and Design of the First Double-Blind, Placebo-Controlled Trial with Allogeneic Adipose Tissue-Derived Stromal Cell Therapy in Patients with Ischemic Heart Failure

    DEFF Research Database (Denmark)

    Kastrup, Jens; Schou, Morten; Gustafsson, Ida

    2017-01-01

    BACKGROUND: Ischemic heart failure (IHF) has a poor prognosis in spite of optimal therapy. We have established a new allogeneic Cardiology Stem Cell Centre adipose-derived stromal cell (CSCC_ASC) product from healthy donors. It is produced without animal products, in closed bioreactor systems...

  5. Cell Therapies for Heart Function Recovery: Focus on Myocardial Tissue Engineering and Nanotechnologies

    Directory of Open Access Journals (Sweden)

    Marie-Noëlle Giraud

    2012-01-01

    Full Text Available Cell therapies have gained increasing interest and developed in several approaches related to the treatment of damaged myocardium. The results of multiple clinical trials have already been reported, almost exclusively involving the direct injection of stem cells. It has, however, been postulated that the efficiency of injected cells could possibly be hindered by the mechanical trauma due to the injection and their low survival in the hostile environment. It has indeed been demonstrated that cell mortality due to the injection approaches 90%. Major issues still need to be resolved and bed-to-bench followup is paramount to foster clinical implementations. The tissue engineering approach thus constitutes an attractive alternative since it provides the opportunity to deliver a large number of cells that are already organized in an extracellular matrix. Recent laboratory reports confirmed the interest of this approach and already encouraged a few groups to investigate it in clinical studies. We discuss current knowledge regarding engineered tissue for myocardial repair or replacement and in particular the recent implementation of nanotechnological approaches.

  6. Regenerative cell therapy and pharmacotherapeutic intervention in heart failure Part 2 : Pharmacological targets, agents and intervention perspectives

    NARCIS (Netherlands)

    Qian, C.; Schoemaker, R. G.; van Gilst, W. H.; Yu, B.; Roks, A. J. M.

    2008-01-01

    Regenerative medicine represents a promising perspective on therapeutic angiogenesis in patients with cardiovascular disease, including heart failure. However, previous or ongoing clinical trials show ambiguous outcomes with respect to the benefit of regenerative therapy by means of bone marrow stem

  7. Right ventricular failure secondary to chronic overload in congenital heart diseases: benefits of cell therapy using human embryonic stem cell-derived cardiac progenitors.

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    Lambert, Virginie; Gouadon, Elodie; Capderou, André; Le Bret, Emmanuel; Ly, Mohamed; Dinanian, Sylvie; Renaud, Jean-Francois; Pucéat, Michel; Rücker-Martin, Catherine

    2015-03-01

    Despite the increasing incidence of right ventricular (RV) failure in adult patients with congenital heart disease, current therapeutic options are still limited. By contrast to left-heart diseases, cell-based myocardial regeneration applied to the right ventricle is poorly studied, even though it may be a therapeutic solution. As human embryonic stem cell-derived cardiac progenitors seem to be good candidates owing to their proliferation capacity, our aim was to assess, in a large animal model of overloaded RV dysfunction, the feasibility and effects of such a cell therapy. Human MesP1(+)/SSEA-1(+) cardiogenic mesodermal cells were administered using multiple intramyocardial injections 4 months after a surgical procedure mimicking the repaired tetralogy of Fallot, and their effects were observed 3 months later on hemodynamic, rhythmic, and histologic parameters. All pigs (sham n = 6, treated n = 6) survived without complication, and cell therapy was clinically well tolerated. Although functional, contractility, and energetics parameters evolved similarly in both groups, benefits regarding arrhythmic susceptibility were observed in the treated group, associated with a significant decrease of peri-myocyte fibrosis (5.71% ± 2.49% vs 12.12% ± 1.85%; P cells could be detected within the myocardium. Cell therapy using intramyocardial injections of human MesP1(+)/SSEA-1(+) cardiogenic mesodermal cells seems to have benefits regarding overloaded RV tissue remodeling and arrhythmic susceptibility, but this mode of administration is not sufficient to obtain a significant improvement in RV function. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  8. [Diuretic therapy in heart failure].

    Science.gov (United States)

    Trullàs, Joan Carles; Morales-Rull, José Luís; Formiga, Francesc

    2014-02-20

    Many of the primary clinical manifestations of heart failure (HF) are due to fluid retention, and treatments targeting congestion play a central role in HF management. Diuretic therapy remains the cornerstone of congestion treatment, and diuretics are prescribed to the majority of HF patients. Despite this ubiquitous use, there is limited evidence from prospective randomized studies to guide the use of diuretics. With the chronic use of diuretic and usually in advanced stages of HF, diuretics may fail to control salt and water retention. This review describes the mechanism of action of available diuretic classes, reviews their clinical use based on scientific evidence and discusses strategies to overcome diuretic resistance. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  9. Potential for stem cell use in congenital heart disease.

    Science.gov (United States)

    Pincott, Emma Siân; Burch, Michael

    2012-03-01

    This article reports on the evolving field of stem cell therapy and its impact on the management of cardiac pathology, in particular congenital heart disease. To date, stem cell therapy has focused on cardiomyoplasty for heart muscle disease, stem cell therapies are already in clinical use for these disorders. Research is now also supporting the potential role of stem cell therapy for congenital heart disease. In the future it may be possible to use stem cells to create cellular grafts and structures that may be surgically implanted into the disordered heart using bioengineering technology. Different types of stem cells have been evaluated and the identification of specific cardiac stem cells offers great potential. Preliminary animal studies investigating fetal cardiac therapies are also underway. These new directions for stem cell research provide exciting potential for the future management of congenital heart disease.

  10. Benefit of cardiopoietic mesenchymal stem cell therapy on left ventricular remodelling: results from the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) study.

    Science.gov (United States)

    Teerlink, John R; Metra, Marco; Filippatos, Gerasimos S; Davison, Beth A; Bartunek, Jozef; Terzic, Andre; Gersh, Bernard J; Povsic, Thomas J; Henry, Timothy D; Alexandre, Bertrand; Homsy, Christian; Edwards, Christopher; Seron, Aymeric; Wijns, William; Cotter, Gad

    2017-11-01

    Left ventricular (LV) reverse remodelling is an important marker of improved outcomes in patients with advanced heart failure (HF). We examined the impact of the intramyocardial administration of bone-marrow-derived, lineage-directed, autologous cardiopoietic mesenchymal stem cells (C3BS-CQR-1) on LV remodelling in patients with advanced HF enrolled in the CHART-1 study. Patients (n=351) with symptomatic advanced HF secondary to ischaemic heart disease, and reduced LV ejection fraction (LVEF CHART-1, intramyocardial administration of cardiopoietic stem cells led to reverse remodelling as evidenced by significant progressive decreases in LVEDV and LVESV through the 52 weeks of follow-up. Further studies are needed to explore the dose response with regard to cell number and injected volume, and reverse remodelling. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

  11. Hormone Replacement Therapy and Your Heart

    Science.gov (United States)

    Hormone replacement therapy and your heart Are you taking — or considering — hormone therapy to treat bothersome menopausal symptoms? Understand ... for you. By Mayo Clinic Staff Long-term hormone replacement therapy used to be routinely prescribed for postmenopausal women ...

  12. Production Assistance for Cellular Therapies (PACT): four-year experience from the United States National Heart, Lung, and Blood Institute (NHLBI) contract research program in cell and tissue therapies.

    Science.gov (United States)

    Reed, William; Noga, Stephen J; Gee, Adrian P; Rooney, Cliona M; Wagner, John E; McCullough, Jeffrey; McKenna, David H; Whiteside, Theresa L; Donnenberg, Albert D; Baker, Acacia K; Lindblad, Robert W; Wagner, Elizabeth L; Mondoro, Traci Heath

    2009-04-01

    In 2002, the US National Heart, Lung, and Blood Institute (NHLBI) conducted a workshop to determine needs of the cell therapy community. A consensus emerged that improved access to cGMP facilities, regulatory assistance, and training would foster the advancement of cellular therapy. A 2003 NHLBI request for proposals resulted in four contracts being awarded to three cell-manufacturing facilities (Baylor College of Medicine, University of Minnesota, and University of Pittsburgh) and one administrative center (The EMMES Corporation). As a result, Production Assistance for Cellular Therapies (PACT) was formed. As of October 1, 2008, PACT has received 65 preliminary applications of which 45 have been approved for product manufacture. A variety of cell therapies are represented including T-regulatory cells, natural killer cells, adipose-derived stem cells, cardiac progenitor cells for cardiac disease, hematopoietic progenitor cells (HPCs) for central nervous system applications, cytotoxic T lymphocytes, and dendritic cells. A total of 169 products have been administered under 12 applications and 2 reagents were manufactured and delivered. Fourteen peer-reviewed publications and 15 abstracts have resulted from the PACT project to date. A cell therapy textbook is nearly complete. PACT technical projects have addressed assay development, rapid endotoxin testing, shipping of cell products, and CD34+ HPC isolation from low-volume marrow. Educational Web seminars and on-site training through workshops have been conducted. PACT is an active and successful cell therapy manufacturing resource in the United States, addressing research and training while forging relationships among academia, industry, and participating institutions.

  13. 31P NMR 2D Mapping of Creatine Kinase Forward Flux Rate in Hearts with Postinfarction Left Ventricular Remodeling in Response to Cell Therapy.

    Directory of Open Access Journals (Sweden)

    Ling Gao

    Full Text Available Utilizing a fast 31P magnetic resonance spectroscopy (MRS 2-dimensional chemical shift imaging (2D-CSI method, this study examined the heterogeneity of creatine kinase (CK forward flux rate of hearts with postinfarction left ventricular (LV remodeling. Immunosuppressed Yorkshire pigs were assigned to 4 groups: 1 A sham-operated normal group (SHAM, n = 6; 2 A 60 minutes distal left anterior descending coronary artery ligation and reperfusion (MI, n = 6; 3 Open patch group; ligation injury plus open fibrin patch over the site of injury (Patch, n = 6; and 4 Cell group, hiPSCs-cardiomyocytes, -endothelial cells, and -smooth muscle cells (2 million, each were injected into the injured myocardium pass through a fibrin patch (Cell+Patch, n = 5. At 4 weeks, the creatine phosphate (PCr/ATP ratio, CK forward flux rate (Flux PCr→ATP, and k constant of CK forward flux rate (kPCr→ATP were severely decreased at border zone myocardium (BZ adjacent to MI. Cell treatment results in significantly increase of PCr/ATP ratio and improve the value of kPCr→ATP and Flux PCr→ATP in BZ myocardium. Moreover, the BZ myocardial CK total activity and protein expression of CK mitochondria isozyme and CK myocardial isozyme were significantly reduced, but recovered in response to cell treatment. Thus, cell therapy results in improvement of BZ bioenergetic abnormality in hearts with postinfarction LV remodeling, which is accompanied by significantly improvements in BZ CK activity and CK isozyme expression. The fast 2D 31P MR CSI mapping can reliably measure the heterogeneity of bioenergetics in hearts with post infarction LV remodeling.

  14. Vitamin therapy after heart transplantation.

    Science.gov (United States)

    Patel, Jignesh

    2015-10-01

    The need for routine nutritional supplementation with vitamins in most healthy individuals remains a matter of debate and current guidelines recommend that the need for these essential nutrients be met primarily through consuming an adequate diet. However, after heart transplantation, multiple factors, including the effects of prolonged debilitation prior to surgery and immunosuppression, may lead to physiological stress, which may justify consideration for vitamin supplementation. In general, clinical trials have not focused on vitamin supplementation after heart transplantation. There appears to be some limited clinical data to support the use of certain vitamins after heart transplantation. In particular, the putative antioxidant properties of vitamins C and E after heart transplantation may be beneficial as prophylaxis against cardiac allograft vasculopathy, and vitamin D, in conjunction with calcium, may help prevent post-transplant bone loss. Current guidelines only address the use of vitamin D after heart transplantation.

  15. Biomarker Guided Therapy in Chronic Heart Failure

    Science.gov (United States)

    Bektas, Sema

    2015-01-01

    This review article addresses the question of whether biomarker-guided therapy is ready for clinical implementation in chronic heart failure. The most well-known biomarkers in heart failure are natriuretic peptides, namely B-type natriuretic peptide (BNP) and N-terminal pro-BNP. They are well-established in the diagnostic process of acute heart failure and prediction of disease prognosis. They may also be helpful in screening patients at risk of developing heart failure. Although studied by 11 small- to medium-scale trials resulting in several positive meta-analyses, it is less well-established whether natriuretic peptides are also helpful for guiding chronic heart failure therapy. This uncertainty is expressed by differences in European and American guideline recommendations. In addition to reviewing the evidence surrounding the use of natriuretic peptides to guide chronic heart failure therapy, this article gives an overview of the shortcomings of the trials, how the results may be interpreted and the future directions necessary to fill the current gaps in knowledge. Therapy guidance in chronic heart failure using other biomarkers has not been prospectively tested to date. Emerging biomarkers, such as galectin-3 and soluble ST2, might be useful in this regard, as suggested by several post-hoc analyses. PMID:28785440

  16. [Therapy of terminal heart failure using heart transplantation].

    Science.gov (United States)

    Hummel, M; Warnecke, H; Schüler, S; Hempel, B; Spiegelsberger, S; Hetzer, R

    1991-08-16

    Heart transplantation (HTx) has now become an accepted treatment modality for end-stage heart disease. The limited supply of suitable donor organs imposes constraints upon the decision of who should be selected for transplantation. Usually patients are candidates for HTx, who remain NYHA functional class III or IV despite maximal medical therapy. Further criteria are low left ventricular ejection fraction (less than 20%) with heart rhythm disturbances class IIIA-V (LOWN), which are associated with poor prognosis. Additionally, the suffering of the patient and also the course of heart failure are essential for judging the urgency of HTx. Contraindications are absolute in patients with untreated infections, fixed pulmonary vascular resistance (PVR) above 8 WOOD-degrees, severe irreversible kidney and liver disease, active ventricular or duodenal ulcers and acute, psychiatric illness. HTx is relatively contraindicated in patients with diabetes mellitus, age over 60 years, PVR above 6 WOOD-degrees and an unstable psychosocial situation. To prevent rejection of the transplant heart, live-long immunosuppressive therapy is needed. Most immunosuppressive regimes consist of Cyclosporine A and Azathioprine (double drug therapy) or in combination (tripple drug therapy) with Prednisolone. For monitoring of this therapy, control of hole blood cyclosporine A level and white blood count is needed. Rejection episodes can be suspected if there is a greater than 20 mmHg decrease of systolic blood pressure, elevated body temperature, malaise, tachycardia or heart rhythm disturbance. The diagnosis of cardiac rejection can be established by endomyocardial biopsy. Measurement of the voltage of either the surface or intramyocardial ECG, echocardiography with special consideration to early left ventricular filling time as well as immunological methods are additionally used tools. Graft sclerosis as the main risk factor of the late transplant period remains an unsolved problem.

  17. Effects of simvastatin/ezetimibe on microparticles, endothelial progenitor cells and platelet aggregation in subjects with coronary heart disease under antiplatelet therapy

    Energy Technology Data Exchange (ETDEWEB)

    Camargo, L.M.; França, C.N.; Izar, M.C.; Bianco, H.T.; Lins, L.S.; Barbosa, S.P.; Pinheiro, L.F.; Fonseca, F.A.H. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Medicina, São Paulo, SP, Brasil, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2014-04-15

    It is not known whether the addition of ezetimibe to statins adds cardiovascular protection beyond the expected changes in lipid levels. Subjects with coronary heart disease were treated with four consecutive 1-week courses of therapy (T) and evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133; CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was examined by flow-mediated dilation. Comparisons between therapies revealed differences in lipids (T2 and T3T1 and T4, P=0.001). Decreased platelet aggregation was observed after aspirin (arachidonic acid, T1therapy. Simvastatin/ezetimibe diphosphate did not change platelet aggregation, the amount of circulating endothelial and platelet microparticles, or endothelial progenitor cells. Cardiovascular protection following therapy with simvastatin/ezetimibe seems restricted to lipid changes and improvement of endothelial function not affecting the release of microparticles, mobilization of endothelial progenitor cells or decreased platelet aggregation.

  18. Granulocyte-colony stimulating factor therapy to induce neovascularization in ischemic heart disease

    DEFF Research Database (Denmark)

    Ripa, Rasmus Sejersten

    2012-01-01

    Cell based therapy for ischemic heart disease has the potential to reduce post infarct heart failure and chronic ischemia. Treatment with granulocyte-colony stimulating factor (G-CSF) mobilizes cells from the bone marrow to the peripheral blood. Some of these cells are putative stem or progenitor...

  19. Gene network analysis: from heart development to cardiac therapy.

    Science.gov (United States)

    Ferrazzi, Fulvia; Bellazzi, Riccardo; Engel, Felix B

    2015-03-01

    Networks offer a flexible framework to represent and analyse the complex interactions between components of cellular systems. In particular gene networks inferred from expression data can support the identification of novel hypotheses on regulatory processes. In this review we focus on the use of gene network analysis in the study of heart development. Understanding heart development will promote the elucidation of the aetiology of congenital heart disease and thus possibly improve diagnostics. Moreover, it will help to establish cardiac therapies. For example, understanding cardiac differentiation during development will help to guide stem cell differentiation required for cardiac tissue engineering or to enhance endogenous repair mechanisms. We introduce different methodological frameworks to infer networks from expression data such as Boolean and Bayesian networks. Then we present currently available temporal expression data in heart development and discuss the use of network-based approaches in published studies. Collectively, our literature-based analysis indicates that gene network analysis constitutes a promising opportunity to infer therapy-relevant regulatory processes in heart development. However, the use of network-based approaches has so far been limited by the small amount of samples in available datasets. Thus, we propose to acquire high-resolution temporal expression data to improve the mathematical descriptions of regulatory processes obtained with gene network inference methodologies. Especially probabilistic methods that accommodate the intrinsic variability of biological systems have the potential to contribute to a deeper understanding of heart development.

  20. Stem cell therapy for myocardial infarction

    NARCIS (Netherlands)

    A.D. Moelker (Amber)

    2007-01-01

    textabstractCoronary heart disease and heart failure continue to be significant burdens to healthcare systems in the Western world and are predicted to become so in emerging economies. Despite mixed results in both experimental and clinical studies, stem cell therapy is a promising option for

  1. Stem cell therapy for myocardial infarction

    OpenAIRE

    Moelker, Amber

    2007-01-01

    textabstractCoronary heart disease and heart failure continue to be significant burdens to healthcare systems in the Western world and are predicted to become so in emerging economies. Despite mixed results in both experimental and clinical studies, stem cell therapy is a promising option for patients suffering from myocardial infarction or patients with chronic heart failure after myocardial infarction. However, many issues in the field of cellular cardiomyoplasty still need to be resolved. ...

  2. The new concept of ''interventional heart failure therapy'': part 2--inotropes, valvular disease, pumps, and transplantation.

    Science.gov (United States)

    Thompson, Keith A; Philip, Kiran J; Simsir, Sinan; Schwarz, Ernst R

    2010-09-01

    Recent advances in heart failure therapy include a variety of mechanical and device-based technologies that target structural aspects of heart failure that cannot be treated with drug therapy alone; these newer therapies can collectively be described as interventional heart failure therapy. This article is the second in a 2-part series reviewing interventional heart failure therapy. Interventions included in this discussion include those indicated for the treatment of end-stage refractory heart failure, including interventional medical therapy, interventional treatment of valvular disease, mechanical assist devices, and heart transplantation. Also included is a review of the currently available catheter-based pumps, which are intended to provide temporary support in patients with acute hemodynamic compromise. The use of cellular or stem cell therapy for the treatment of heart failure is an emerging interventional therapy and data supporting its use for the treatment heart failure will also be presented, as will a discussion of the role of palliative care and self-care in heart failure therapy.

  3. Bone marrow progenitor cell therapy-mediated paracrine regulation of cardiac miRNA-155 modulates fibrotic response in diabetic hearts.

    Science.gov (United States)

    Kishore, Raj; Verma, Suresh K; Mackie, Alexander R; Vaughan, Erin E; Abramova, Tatiana V; Aiko, Ito; Krishnamurthy, Prasanna

    2013-01-01

    Diabetes is associated with a higher incidence of myocardial infarction (MI) and increased risk for adverse vascular and fibrogenic events post-MI. Bone marrow-derived progenitor cell (BMPC) therapy has been shown to promote neovascularization, decrease infarct area and attenuate left ventricular (LV) dysfunction after MI. Unlike vascular effects, the anti-fibrosis mechanisms of BMPC, specifically under diabetic conditions, are poorly understood. We demonstrated that intramyocardial delivery of BMPCs in infarcted diabetic db/db mice significantly down-regulates profibrotic miRNA-155 in the myocardium and improves LV remodeling and function. Furthermore, inhibition of paracrine factor hepatocyte growth factor (HGF) signaling in vivo suppressed the BMPC-mediated inhibition of miR-155 expression and the associated protective effect on cardiac fibrosis and function. In vitro studies confirmed that the conditioned media of BMPC inhibited miR-155 expression and profibrotic signaling in mouse cardiac fibroblasts under diabetic conditions. However, neutralizing antibodies directed against HGF blocked these effects. Furthermore, miR-155 over-expression in mouse cardiac fibroblasts inhibited antifibrotic Sloan-Kettering Institute proto-oncogene (Ski) and Ski-related novel gene, non-Alu-containing (SnoN) signaling and abrogated antifibrogenic response of HGF. Together, our data demonstrates that paracrine regulation of cardiac miRNAs by transplanted BMPCs contributes to the antifibrotic effects of BMPC therapy. BMPCs release HGF, which inhibits miR-155-mediated profibrosis signaling, thereby preventing cardiac fibrosis. These data suggest that targeting miR-155 might serve as a potential therapy against cardiac fibrosis in the diabetic heart.

  4. Bone marrow progenitor cell therapy-mediated paracrine regulation of cardiac miRNA-155 modulates fibrotic response in diabetic hearts.

    Directory of Open Access Journals (Sweden)

    Raj Kishore

    Full Text Available Diabetes is associated with a higher incidence of myocardial infarction (MI and increased risk for adverse vascular and fibrogenic events post-MI. Bone marrow-derived progenitor cell (BMPC therapy has been shown to promote neovascularization, decrease infarct area and attenuate left ventricular (LV dysfunction after MI. Unlike vascular effects, the anti-fibrosis mechanisms of BMPC, specifically under diabetic conditions, are poorly understood. We demonstrated that intramyocardial delivery of BMPCs in infarcted diabetic db/db mice significantly down-regulates profibrotic miRNA-155 in the myocardium and improves LV remodeling and function. Furthermore, inhibition of paracrine factor hepatocyte growth factor (HGF signaling in vivo suppressed the BMPC-mediated inhibition of miR-155 expression and the associated protective effect on cardiac fibrosis and function. In vitro studies confirmed that the conditioned media of BMPC inhibited miR-155 expression and profibrotic signaling in mouse cardiac fibroblasts under diabetic conditions. However, neutralizing antibodies directed against HGF blocked these effects. Furthermore, miR-155 over-expression in mouse cardiac fibroblasts inhibited antifibrotic Sloan-Kettering Institute proto-oncogene (Ski and Ski-related novel gene, non-Alu-containing (SnoN signaling and abrogated antifibrogenic response of HGF. Together, our data demonstrates that paracrine regulation of cardiac miRNAs by transplanted BMPCs contributes to the antifibrotic effects of BMPC therapy. BMPCs release HGF, which inhibits miR-155-mediated profibrosis signaling, thereby preventing cardiac fibrosis. These data suggest that targeting miR-155 might serve as a potential therapy against cardiac fibrosis in the diabetic heart.

  5. Bone Marrow Progenitor Cell Therapy-Mediated Paracrine Regulation of Cardiac miRNA-155 Modulates Fibrotic Response in Diabetic Hearts

    Science.gov (United States)

    Kishore, Raj; Verma, Suresh K.; Mackie, Alexander R.; Vaughan, Erin E.; Abramova, Tatiana V.; Aiko, Ito; Krishnamurthy, Prasanna

    2013-01-01

    Diabetes is associated with a higher incidence of myocardial infarction (MI) and increased risk for adverse vascular and fibrogenic events post-MI. Bone marrow-derived progenitor cell (BMPC) therapy has been shown to promote neovascularization, decrease infarct area and attenuate left ventricular (LV) dysfunction after MI. Unlike vascular effects, the anti-fibrosis mechanisms of BMPC, specifically under diabetic conditions, are poorly understood. We demonstrated that intramyocardial delivery of BMPCs in infarcted diabetic db/db mice significantly down-regulates profibrotic miRNA-155 in the myocardium and improves LV remodeling and function. Furthermore, inhibition of paracrine factor hepatocyte growth factor (HGF) signaling in vivo suppressed the BMPC-mediated inhibition of miR-155 expression and the associated protective effect on cardiac fibrosis and function. In vitro studies confirmed that the conditioned media of BMPC inhibited miR-155 expression and profibrotic signaling in mouse cardiac fibroblasts under diabetic conditions. However, neutralizing antibodies directed against HGF blocked these effects. Furthermore, miR-155 over-expression in mouse cardiac fibroblasts inhibited antifibrotic Sloan-Kettering Institute proto-oncogene (Ski) and Ski-related novel gene, non-Alu-containing (SnoN) signaling and abrogated antifibrogenic response of HGF. Together, our data demonstrates that paracrine regulation of cardiac miRNAs by transplanted BMPCs contributes to the antifibrotic effects of BMPC therapy. BMPCs release HGF, which inhibits miR-155-mediated profibrosis signaling, thereby preventing cardiac fibrosis. These data suggest that targeting miR-155 might serve as a potential therapy against cardiac fibrosis in the diabetic heart. PMID:23560074

  6. [Diuretic therapy in acute heart failure].

    Science.gov (United States)

    Trullàs, Joan Carles; Morales-Rull, José Luis; Formiga, Francesc

    2014-03-01

    Diuretics are widely recommended in patients with acute heart failure (AHF). Unfortunately, despite their widespread use, limited data are available from randomized clinical trials to guide clinicians on the appropriate management of diuretic therapy. Loop diuretics are considered the first-line diuretic therapy, especially intravenous furosemide, but the best mode of administration (high-dose versus low-dose and continuous infusion versus bolus) is unclear. When diuretic resistance develops, different therapeutic strategies can be adopted, including combined diuretic therapy with thiazide diuretics and/or aldosterone antagonists. Low or "non-diuretic" doses (25-50mg QD) of aldosterone antagonists have been demonstrated to confer a survival benefit in patients with heart failure and reduced ejection fraction and consequently should be prescribed in all such patients, unless contraindicated by potassium and/or renal function values. There is less evidence on the use of aldosterone antagonists at higher or "diuretic" doses (≥ 100mg QD) but these drugs could be useful in relieving congestive symptoms in combination with furosemide. Thiazide diuretics can also be helpful as they have synergic effects with loop diuretics by inhibiting sodium reabsorption in distal parts of the nephron. The effect of diuretic therapy in AHF should be monitored with careful observation of clinical signs and symptoms of congestion. Serum electrolytes and kidney function should also be monitored during the use of intravenous diuretics. Copyright © 2014 Elsevier España, S.L. All rights reserved.

  7. Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial design.

    Science.gov (United States)

    Bartunek, Jozef; Davison, Beth; Sherman, Warren; Povsic, Thomas; Henry, Timothy D; Gersh, Bernard; Metra, Marco; Filippatos, Gerasimos; Hajjar, Roger; Behfar, Atta; Homsy, Christian; Cotter, Gad; Wijns, William; Tendera, Michal; Terzic, Andre

    2016-02-01

    Cardiopoiesis is a conditioning programme that aims to upgrade the cardioregenerative aptitude of patient-derived stem cells through lineage specification. Cardiopoietic stem cells tested initially for feasibility and safety exhibited signs of clinical benefit in patients with ischaemic heart failure (HF) warranting definitive evaluation. Accordingly, CHART-1 is designed as a large randomized, sham-controlled multicentre study aimed to validate cardiopoietic stem cell therapy. Patients (n = 240) with chronic HF secondary to ischaemic heart disease, reduced LVEF (Heart Failure Questionnaire score, 6 min walk test, LV end-systolic volume, and LVEF at 9 months. The secondary efficacy endpoint is the time to cardiovascular death or worsening HF at 12 months. Safety endpoints include mortality, readmissions, aborted sudden deaths, and serious adverse events at 12 and 24 months. The CHART-1 clinical trial is powered to examine the therapeutic impact of lineage-directed stem cells as a strategy to achieve cardiac regeneration in HF populations. On completion, CHART-1 will offer a definitive evaluation of the efficacy and safety of cardiopoietic stem cells in the treatment of chronic ischaemic HF. NCT01768702. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

  8. Liver failure in total artificial heart therapy.

    Science.gov (United States)

    Dimitriou, Alexandros Merkourios; Dapunt, Otto; Knez, Igor; Wasler, Andrae; Oberwalder, Peter; Koerfer, Reiner; Tenderich, Gero; Spiliopoulos, Sotirios

    2016-07-01

    Congestive hepatopathy (CH) and acute liver failure (ALF) are common among biventricular heart failure patients. We sought to evaluate the impact of total artificial heart (TAH) therapy on hepatic function and associated clinical outcomes. A total of 31 patients received a Syncardia Total Artificial Heart. Preoperatively 17 patients exhibited normal liver function or mild hepatic derangements that were clinically insignificant and did not qualify as acute or chronic liver failure, 5 patients exhibited ALF and 9 various hepatic derangements owing to CH. Liver associated mortality and postoperative course of liver values were prospectively documented and retrospectively analyzed. Liver associated mortality in normal liver function, ALF and CH cases was 0%, 20% (P=0.03) and 44.4% (P=0.0008) respectively. 1/17 (5.8%) patients with a normal liver function developed an ALF, 4/5 (80%) patients with an ALF experienced a markedly improvement of hepatic function and 6/9 (66.6%) patients with CH a significant deterioration. TAH therapy results in recovery of hepatic function in ALF cases. Patients with CH prior to surgery form a high risk group with increased liver associated mortality.

  9. Prompt bone marrow-derived mesenchymal stem cell therapy enables early porcine heart function recovery from acute myocardial infarction.

    Science.gov (United States)

    Fan, Chang-Qing; Leu, Steve; Sheu, Jiunn-Jye; Zhen, Yen-Yi; Tsai, Tzu-Hsien; Chen, Yung-Lung; Chung, Sheng-Ying; Chai, Han-Tan; Sun, Cheuk-Kwan; Yang, Jenq-Lin; Chang, Hsueh-Wen; Ko, Sheung-Fat; Yip, Hon-Kan

    2014-01-01

    Impact of early bone marrow-derived mesenchymal stem cell (BMDMSC) implantation on left ventricular (LV) function after AMI was studied.Twelve mini-pigs were equally divided into placebo (AMI through left coronary artery ligation) and cell-treated groups [BMDMSCs (3.0 × 10(7)) implanted into infarct area (IA)] with myocardium harvested by post-AMI day 90. Six healthy animals served as controls.On post-AMI day 90, magnetic resonance imaging showed a lower LV ejection fraction but higher LV dimensions in the placebo group (P < 0.003) that also had increased IAs but reduced wall thickness (P < 0.005). Pro-apoptotic gene expressions (Bax, caspase-3) and apoptotic nucleus number in IAs and peri-IAs were highest in the placebo group (P < 0.001). Inflammatory biomarker expressions (MMP-9, oxidized protein, CD40+ cells) were highest, whereas those of angiogenesis (VEGF, CD31+ cells, SDF-1α, CXCR4) and myocardium-preservation (connexin43, troponin-I, cytochrome-C) were lowest in the placebo group (P < 0.01).BMDMSC implantation preserved LV function and alleviated remodeling at post-AMI day 90.

  10. Tuning flux: autophagy as a target of heart disease therapy

    Science.gov (United States)

    Xie, Min; Morales, Cyndi R.; Lavandero, Sergio; Hill, Joseph A.

    2013-01-01

    Purpose of review Despite maximum medical and mechanical support therapy, heart failure remains a relentlessly progressive disorder with substantial morbidity and mortality. Autophagy, an evolutionarily conserved process of cellular cannibalization, has been implicated in virtually all forms of cardiovascular disease. Indeed, its role is context dependent, antagonizing or promoting disease depending on the circumstance. Here, we review current understanding of the role of autophagy in the pathogenesis of heart failure and explore this pathway as a target of therapeutic intervention. Recent findings In preclinical models of heart disease, cardiomyocyte autophagic flux is activated; indeed, its role in disease pathogenesis is the subject of intense investigation to define mechanism. Similarly, in failing human heart of a variety of etiologies, cardiomyocyte autophagic activity is upregulated, and therapy, such as with mechanical support systems, elicits declines in autophagy activity. However, when suppression of autophagy is complete, rapid and catastrophic cell death occurs, consistent with a model in which basal autophagic flux is required for proteostasis. Thus, a narrow zone of ‘optimal’ autophagy seems to exist. The challenge moving forward is to tune the stress-triggered autophagic response within that ‘sweet spot’ range for therapeutic benefit. Summary Whereas we have known for some years of the participation of lysosomal mechanisms in heart disease, it is only recently that upstream mechanisms (autophagy) are being explored. The challenge for the future is to dissect the underlying circuitry and titrate the response into an optimal, proteostasis-promoting range in hopes of mitigating the ever-expanding epidemic of heart failure. PMID:21415729

  11. Interleukin-2 receptor antagonists as induction therapy after heart transplantation

    DEFF Research Database (Denmark)

    Møller, Christian H; Gustafsson, Finn; Gluud, Christian

    2008-01-01

    About half of the transplantation centers use induction therapy after heart transplantation. Interleukin-2 receptor antagonists (IL-2Ras) are used increasingly for induction therapy. We conducted a systematic review of randomized trials assessing IL-2Ras.......About half of the transplantation centers use induction therapy after heart transplantation. Interleukin-2 receptor antagonists (IL-2Ras) are used increasingly for induction therapy. We conducted a systematic review of randomized trials assessing IL-2Ras....

  12. Cell Therapy in Dermatology

    Science.gov (United States)

    Petrof, Gabriela; Abdul-Wahab, Alya; McGrath, John A.

    2014-01-01

    Harnessing the regenerative capacity of keratinocytes and fibroblasts from human skin has created new opportunities to develop cell-based therapies for patients. Cultured cells and bioengineered skin products are being used to treat patients with inherited and acquired skin disorders associated with defective skin, and further clinical trials of new products are in progress. The capacity of extracutaneous sources of cells such as bone marrow is also being investigated for its plasticity in regenerating skin, and new strategies, such as the derivation of inducible pluripotent stem cells, also hold great promise for future cell therapies in dermatology. This article reviews some of the preclinical and clinical studies and future directions relating to cell therapy in dermatology, particularly for inherited skin diseases associated with fragile skin and poor wound healing. PMID:24890834

  13. Hematopoietic Stem Cells Therapies.

    Science.gov (United States)

    Chivu-Economescu, Mihaela; Rubach, Martin

    2017-01-01

    Stem cell-based therapies are recognized as a new way to treat various diseases and injuries, with a wide range of health benefits. The goal is to heal or replace diseased or destroyed organs or body parts with healthy new cells provided by stem cell transplantation. The current practical form of stem cell therapy is the hematopoietic stem cells transplant applied for the treatment of hematological disorders. There are over 2100 clinical studies in progress concerning hematopoietic stem cell therapies. All of them are using hematopoietic stem cells to treat various diseases like: cancers, leukemia, lymphoma, cardiac failure, neural disorders, auto-immune diseases, immunodeficiency, metabolic or genetic disorders. Several challenges are to be addressed prior to developing and applying large scale cell therapies: 1) to explain and control the mechanisms of differentiation and development toward a specific cell type needed to treat the disease, 2) to obtain a sufficient number of desired cell type for transplantation, 3) to overcome the immune rejection and 4) to show that transplanted cells fulfill their normal functions in vivo after transplants. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Drug Therapy for Heart Valve Diseases

    Science.gov (United States)

    Borer, Jeffrey S.; Sharma, Abhishek

    2015-01-01

    Valvular heart diseases (VHDs) are progressive. When not caused by acute comorbidities they are generally characterized by long asymptomatic phases during which hemodynamic severity may progress leading to morbidity and mortality. Treatment depends on VHD type and severity but when severe and symptomatic, usually involves mechanical intervention. Asymptomatic patients, and those who lack objective descriptors associated with high risk, are closely observed clinically with optimization of associated cardiovascular risk factors until surgical indications develop. Though often prescribed based on theory, no rigorous evidence supports pharmacological therapy in most chronic situations though drugs may be appropriate in acute valvular diseases, or as a bridge to surgery in severely decompensated patients. Herein, we examine evidence supporting drug use for chronic VHDs. PMID:26371236

  15. Heart transplant survival in non-human primates : T cell-directed immunosuppressive therapy and regulatory T cells for promotion of heart transplant survival in non-human primates

    NARCIS (Netherlands)

    E.M. Dons (Eefje)

    2013-01-01

    textabstractHeart transplantation significantly enhances the life expectancy of adult patients suffering heart failure, and infants born with malformations of their heart. However, there are many hurdles such as rejection of the transplanted organ, or side effects of the immunosuppressive drugs,

  16. Regenerating the heart - Stem cells and the cardiovascular system

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2012-06-01

    Full Text Available A book dealing with the heart regeneration achieved thanks to cell therapies sounds like an immense challenge considering both how the field rapidily progresses and the necessary interdisciplinarity to exhaustively cover all of the multifaced aspects of the subject. The great modesty that the two editors show up in the Introduction section while writing that they declined the offer to write a book devoted to the heart regeneration is therefore something highly appreciable.....

  17. Stem cell therapy. Use of differentiated pluripotent stem cells as replacement therapy for treating disease

    DEFF Research Database (Denmark)

    Fox, Ira J; Daley, George Q; Goldman, Steven A

    2014-01-01

    Pluripotent stem cells (PSCs) directed to various cell fates holds promise as source material for treating numerous disorders. The availability of precisely differentiated PSC-derived cells will dramatically affect blood component and hematopoietic stem cell therapies and should facilitate...... treatment of diabetes, some forms of liver disease and neurologic disorders, retinal diseases, and possibly heart disease. Although an unlimited supply of specific cell types is needed, other barriers must be overcome. This review of the state of cell therapies highlights important challenges. Successful...

  18. Left ventricular assist device therapy in advanced heart failure

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Rogers, Joseph G

    2017-01-01

    Despite improvements in pharmacological therapy and pacing, prognosis in advanced heart failure (HF) remains poor, with a 1-year mortality of 25-50%. While heart transplantation provides excellent survival and quality of life for eligible patients, only a few can be offered this treatment due...

  19. [Anti-hypertensive therapies in patients with heart disease].

    Science.gov (United States)

    Tanaka, Komei; Minamino, Tohru

    2015-11-01

    Abstract Hypertension is the major cause of cardiovascular disease. Persistent hypertension leads to cardiovascular remodeling and resulted in heart diseases such as coronary artery disease, heart failure, and arrhythmia. The presence of hypertension could also be a precipitating factor of heart diseases and form vicious cycle. Therefore, perfect blood pressure control is essential for the prevention of cardiovascular events. Additionally, it is ideal to choose anti-hypertensive agents, which have cardiovascular-protective effects as well as strong blood pressure-lowering effects. We herein describe anti-hypertensive therapies in patients with heart disease in accordance with JSH2014 and JCS guidelines.

  20. Anticoagulation Therapy and NOACs in Heart Failure.

    Science.gov (United States)

    Thomas, Isac; EncisoSilva, Jorge; Schlueter, Michelle; Greenberg, Barry

    2017-01-01

    Current evidence indicates that heart failure (HF) confers a hyper-coagulable state that is associated with adverse events including stroke, systemic embolism, and mortality. This may be due to the elevated levels of pro-thrombotic and pro-inflammatory cytokines that are seen in patients with acute and chronic HF. Left ventricular wall motion abnormalities in patients with systolic dysfunction predispose to local thrombosis due to blood stasis as does atrial fibrillation (AF) which leads to blood stasis in regions of the atria. The high risk of thromboemboli in HF patients with AF has resulted in the use anticoagulation therapy to prevent the occurrence of catastrophic events. There is evidence, however, that the pro-inflammatory, pro-thrombotic state that exists in HF puts patients who are in sinus rhythm at risk. The novel oral anticoagulants (NOACs) have been shown in RCT to have at least equivalent efficacy in reducing stroke as warfarin while exposing patients to a lower risk of bleeding. The fact that the NOACs don't require routine monitoring to assure that patients remain within the therapeutic range and have relatively simple dosing requirements and a safer risk profile makes them attractive substitutes to warfarin in HF patients with atrial fibrillation and other conditions (e.g. deep venous thrombosis). Post hoc analyses from a subset of HF patients from the RCTs in AF patients have demonstrated similar findings as were reported in the entire populations that were included in the trials. As a result, NOACS are commonly used now in HF patients with AF. For HF patients with reduced ejection fraction in sinus rhythm, the use of warfarin in randomized clinical trials (RCT) to reduce stroke has been disappointing and associated with increase bleeding risk when compared to aspirin. The advantages of the NOACs over warfarin, however, raise the question of whether they might improve outcomes in HF patients who are in sinus rhythm. The currently ongoing COMMANDER

  1. Drug Therapy for Acute Heart Failure.

    Science.gov (United States)

    Di Somma, Salvatore; Magrini, Laura

    2015-08-01

    Acute heart failure is globally one of most frequent reasons for hospitalization and still represents a challenge for the choice of the best treatment to improve patient outcome. According to current international guidelines, as soon as patients with acute heart failure arrive at the emergency department, the common therapeutic approach aims to improve their signs and symptoms, correct volume overload, and ameliorate cardiac hemodynamics by increasing vital organ perfusion. Recommended treatment for the early management of acute heart failure is characterized by the use of intravenous diuretics, oxygen, and vasodilators. Although these measures ameliorate the patient's symptoms, they do not favorably impact on short- and long-term mortality. Consequently, there is a pressing need for novel agents in acute heart failure treatment with the result that research in this field is increasing worldwide. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  2. Restoration of heart functions using human embryonic stem cells derived heart muscle cells.

    Science.gov (United States)

    Gepstein, Lior; Kehat, Izhak

    2005-02-01

    Extract: Recent advances in molecular and cellular biology and specifically in the areas of stem cell biology and tissue engineering have paved the way for the development of a new field in biomedicine, regenerative medicine. This exciting approach seeks to develop new biological solutions, using the mobilization of endogenous stem cells or delivery of exogenous cells to replace or modify the function of diseased, absent, or malfunctioning tissue. The adult heart represents an attractive candidate for these emerging technologies, since adult cardiomyocytes have limited regenerative capacity. Thus, any significant heart cell loss or dysfunction, such as occurs during heart attack, is mostly irreversible and may lead to the development of progressive heart failure, one of the leading causes of world-wide morbidity and mortality. Similarly, dysfunction of the specialized electrical conduction system within the heart may result in inefficient rhythm initiation or impulse conduction, leading to significant slowing of the heart rate, usually requiring the implantation of a permanent electronic pacemaker. Replacement of the dysfunctional myocardium (heart muscle) by implantation of external heart muscle cells is emerging as a novel paradigm for restoration of the myocardial electromechanical properties, but has been significantly hampered by the paucity of cell sources for human heart cells and by the relatively limited evidence for functional integration between grafted and host cells. The recently described human embryonic stem cell (hESC) lines may provide a possible solution for the aforementioned cell sourcing problem.

  3. Drug Therapy in Adult Congenital Heart Disease.

    Science.gov (United States)

    Contractor, Tahmeed; Levin, Vadim; Mandapati, Ravi

    2017-06-01

    Adults with congenital heart disease are at risk for atrial and ventricular arrhythmias that can lead to an increased morbidity as well as mortality. When catheter ablation is not an option or unsuccessful, antiarrhythmic drugs are the mainstay of treatment. There is limited data on the use of antiarrhythmics in this population. The purpose of this article is to discuss the practical aspects of the use of antiarrhythmics in adults with congenital heart disease. Several tables have been provided to provide clinicians a reference for daily use. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Cardioverter defibrillator therapy as a bridge to heart transplantation.

    Science.gov (United States)

    Trappe, H J; Wenzlaff, P

    1995-03-01

    The prognosis of patients with severely impaired left ventricular function is poor, with an annual mortality rate of about 50%, and the majority die from sudden cardiac death. Heart transplantation is an accepted therapy for patients with end-stage heart disease; however, about 30% of candidates for transplantation die from sudden cardiac death while on the waiting list. It has been shown that implantable cardioverter defibrillator (ICD) therapy has a low surgical mortality and is highly effective in the prevention of sudden death. Therefore, prophylactic ICD implantation may prevent sudden death in patients with end-stage heart disease while on the waiting list, and it is highly probable that patients with an ICD have a greater chance of survival until a donor heart becomes available. However, this hypothesis still has to be proven by prospective studies.

  5. Music therapy, emotions and the heart: a pilot study.

    Science.gov (United States)

    Raglio, Alfredo; Oasi, Osmano; Gianotti, Marta; Bellandi, Daniele; Manzoni, Veronica; Goulene, Karine; Imbriani, Chiara; Badiale, Marco Stramba

    2012-01-01

    The autonomic nervous system plays an important role in the control of cardiac function. It has been suggested that sound and music may have effects on the autonomic control of the heart inducing emotions, concomitantly with the activation of specific brain areas, i.e. the limbic area, and they may exert potential beneficial effects. This study is a prerequisite and defines a methodology to assess the relation between changes in cardiac physiological parameters such as heart rate, QT interval and their variability and the psychological responses to music therapy sessions. We assessed the cardiac physiological parameters and psychological responses to a music therapy session. ECG Holter recordings were performed before, during and after a music therapy session in 8 healthy individuals. The different behaviors of the music therapist and of the subjects have been analyzed with a specific music therapy assessment (Music Therapy Checklist). After the session mean heart rate decreased (p = 0.05), high frequency of heart rate variability tended to be higher and QTc variability tended to be lower. During music therapy session "affect attunements" have been found in all subjects but one. A significant emotional activation was associated to a higher dynamicity and variations of sound-music interactions. Our results may represent the rational basis for larger studies in diferent clinical conditions.

  6. Progress in gene therapy of dystrophic heart disease

    OpenAIRE

    Lai, Y.; Duan, D.

    2012-01-01

    The heart is frequently afflicted in muscular dystrophy. In severe cases, cardiac lesion may directly result in death. Over the years, pharmacological and/or surgical interventions have been the mainstay to alleviate cardiac symptoms in muscular dystrophy patients. Although these traditional modalities remain useful, the emerging field of gene therapy has now provided an unprecedented opportunity to transform our thinking/approach in the treatment of dystrophic heart disease. In fact, the pre...

  7. Cardiac resynchronization therapy in patients with heart failure: systematic review

    Directory of Open Access Journals (Sweden)

    Hernani Pinto de Lemos Júnior

    Full Text Available CONTEXT AND OBJECTIVE: Cardiac resynchronization therapy (CRT has emerged as the predominant electrical treatment strategy for patients on pharmacological therapy who present heart failure with wide QRS and low ejection fraction. The objective of this study was to investigate whether cardiac resynchronization therapy improved mortality and morbidity among patients with heart failure. METHODS: This was a systematic review using the Cochrane Collaboration's methodology. The online search strategy included the Cochrane Library, Medline (Medical Literature Analysis and Retrieval System Online, Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde and cardiology congresses from 1990 to 2006. The criteria for considering studies for this review were as follows:-types of studies: randomized controlled trials; types of interventions: cardiac resynchronization therapy compared with other therapies; types of participants: patients with heart failure with low ejection fraction and wide QRS; outcomes: death or hospitalization. RESULTS: Seven trials met the selection criteria. The risk of death due to congestive heart failure was nonsignificant: relative risk (RR, 0.79; 95% confidence interval (CI: 0.60 to 1.03. There was an absolute risk reduction of 4% in all-cause mortality for the experimental group #&091;RR 0.70; CI: 0.60 to 0.83; number needed to treat (NNT 25#&093;; sudden cardiac death showed a statistically significant difference favoring the experimental group, with absolute risk reduction of 1% (CI: 0.46 to 0.96; RR 0.67; NNT 100. There was an absolute risk reduction of 9% for hospitalization due to heart failure (RR 0.64; CI: 0.50 to 0.80; NNT 11 in the experimental group. CONCLUSIONS: Patients receiving CRT had a significantly lower risk of hospitalization due to heart failure, but death rates due to heart failure were similar.

  8. Cells and Angiogenic Cytokines in Therapeutic Angiogenesis for Ischemic Heart Disease

    DEFF Research Database (Denmark)

    Luo, Yu; Zhang, Dai-Fu; Liang, Bo

    2005-01-01

    In the past 20 to 30 years,great developments had been achieved in the applying of cells and angiogenic cytokines for ischemic heart disease.The thesis reviews latest studies of mechanism and clinic application of this novel therapy.......In the past 20 to 30 years,great developments had been achieved in the applying of cells and angiogenic cytokines for ischemic heart disease.The thesis reviews latest studies of mechanism and clinic application of this novel therapy....

  9. Progress in gene therapy of dystrophic heart disease.

    Science.gov (United States)

    Lai, Y; Duan, D

    2012-06-01

    The heart is frequently afflicted in muscular dystrophy. In severe cases, cardiac lesion may directly result in death. Over the years, pharmacological and/or surgical interventions have been the mainstay to alleviate cardiac symptoms in muscular dystrophy patients. Although these traditional modalities remain useful, the emerging field of gene therapy has now provided an unprecedented opportunity to transform our thinking/approach in the treatment of dystrophic heart disease. In fact, the premise is already in place for genetic correction. Gene mutations have been identified and animal models are available for several types of muscular dystrophy. Most importantly, innovative strategies have been developed to effectively deliver therapeutic genes to the heart. Dystrophin-deficient Duchenne cardiomyopathy is associated with Duchenne muscular dystrophy (DMD), the most common lethal muscular dystrophy. Considering its high incidence, there has been a considerable interest and significant input in the development of Duchenne cardiomyopathy gene therapy. Using Duchenne cardiomyopathy as an example, here we illustrate the struggles and successes experienced in the burgeoning field of dystrophic heart disease gene therapy. In light of abundant and highly promising data with the adeno-associated virus (AAV) vector, we have specially emphasized on AAV-mediated gene therapy. Besides DMD, we have also discussed gene therapy for treating cardiac diseases in other muscular dystrophies such as limb-girdle muscular dystrophy.

  10. Bioengineering and Stem Cell Technology in the Treatment of Congenital Heart Disease

    Science.gov (United States)

    Bosman, Alexis; Edel, Michael J.; Blue, Gillian; Dilley, Rodney J.; Harvey, Richard P.; Winlaw, David S.

    2015-01-01

    Congenital heart disease places a significant burden on the individual, family and community despite significant advances in our understanding of aetiology and treatment. Early research in ischaemic heart disease has paved the way for stem cell technology and bioengineering, which promises to improve both structural and functional aspects of disease. Stem cell therapy has demonstrated significant improvements in cardiac function in adults with ischaemic heart disease. This finding, together with promising case studies in the paediatric setting, demonstrates the potential for this treatment in congenital heart disease. Furthermore, induced pluripotent stems cell technology, provides a unique opportunity to address aetiological, as well as therapeutic, aspects of disease. PMID:26239354

  11. Antithrombotic Therapy in Patients with Prosthetic Heart Valves

    Directory of Open Access Journals (Sweden)

    Mohamed HA

    2009-01-01

    Full Text Available Patients with mechanical valve prostheses require a lifelong anticoagulant treatment. The combined use of Warfarin and low-dose aspirin appears to reduce the risk of valve thrombosis and systemic embolism at a low risk of bleeding. The management of women with prosthetic heart valves during pregnancy poses a particular challenge, as there are no available controlled clinical trials to provide guidelines for effective antithrombotic therapy. Oral anticoagulants, such as Warfarin, cause foetal embryopathy; unfractionated heparin and low-molecular-weight heparin have been reported to be ineffective in preventing thromboembolic complications.This article discusses the available data and the most recent guidelines in the antithrombotic management of patients with prosthetic valves, and antithrombotic therapy in various clinical situations such as pregnant women with prosthetic heart valves, and patients with prosthetic heart valves undergoing noncardiac surgery.

  12. The case for statin therapy in chronic heart failure

    NARCIS (Netherlands)

    van der Harst, Pim; Boehm, Michael; van Gilst, Wiek H.; van Veldhuisen, Dirk J.

    Both primary and secondary prevention studies have provided a wealth of evidence that statin therapy effectively reduces cardiovascular events. However, this general statement on the efficacy and safety of statin treatment has not been validated in patients with chronic heart failure (CHF).

  13. Destination therapy--time for a paradigm change in heart failure therapy.

    Science.gov (United States)

    Wilhelm, Markus J; Ruschitzka, Frank; Falk, Volkmar

    2013-03-25

    Heart transplantation is only available for a limited number of patients with end-stage heart failure. Since the arrival of newer ventricular assist devices, mechanical circulatory support constitutes an alternative therapy for patients with advanced heart failure. The first-generation of pulsatile-flow devices were used only for bridging the sickest patients to transplantation. Frequent adverse events, limited durability and the patients' discomfort made them unsuitable for lifetime support. The second-generation continuous-flow devices were smaller, quieter and more durable. Survival rates of patients improved significantly. This led to a marked growth of device implantations, largely caused by an increase of lifetime support. Survival of destination therapy patients is somewhat inferior to the survival of bridge-to-transplant patients, in part due to their co-morbid conditions which limit life expectancy. A subgroup of patients on destination therapy with advanced, but stable heart failure and a low-risk profile reach short-term survival rates equal or superior to the survival after heart transplantation. These patients may be offered the choice of destination therapy versus heart transplantation. However it remains unclear if long-term survival, quality of life and functional status on lifetime support can compete with the excellent results after transplantation. A trend to implanting devices at earlier stages of heart failure has begun. In a current trial, patients with advanced, but stable heart failure are randomised to destination therapy versus optimal medical therapy. The results of this trial will be expected to more precisely determine the place of mechanical circulatory support in the treatment of advanced heart failure.

  14. TOPICAL REVIEW: Stem cells engineering for cell-based therapy

    Science.gov (United States)

    Taupin, Philippe

    2007-09-01

    Stem cells carry the promise to cure a broad range of diseases and injuries, from diabetes, heart and muscular diseases, to neurological diseases, disorders and injuries. Significant progresses have been made in stem cell research over the past decade; the derivation of embryonic stem cells (ESCs) from human tissues, the development of cloning technology by somatic cell nuclear transfer (SCNT) and the confirmation that neurogenesis occurs in the adult mammalian brain and that neural stem cells (NSCs) reside in the adult central nervous system (CNS), including that of humans. Despite these advances, there may be decades before stem cell research will translate into therapy. Stem cell research is also subject to ethical and political debates, controversies and legislation, which slow its progress. Cell engineering has proven successful in bringing genetic research to therapy. In this review, I will review, in two examples, how investigators are applying cell engineering to stem cell biology to circumvent stem cells' ethical and political constraints and bolster stem cell research and therapy.

  15. Stem cells engineering for cell-based therapy.

    Science.gov (United States)

    Taupin, Philippe

    2007-09-01

    Stem cells carry the promise to cure a broad range of diseases and injuries, from diabetes, heart and muscular diseases, to neurological diseases, disorders and injuries. Significant progresses have been made in stem cell research over the past decade; the derivation of embryonic stem cells (ESCs) from human tissues, the development of cloning technology by somatic cell nuclear transfer (SCNT) and the confirmation that neurogenesis occurs in the adult mammalian brain and that neural stem cells (NSCs) reside in the adult central nervous system (CNS), including that of humans. Despite these advances, there may be decades before stem cell research will translate into therapy. Stem cell research is also subject to ethical and political debates, controversies and legislation, which slow its progress. Cell engineering has proven successful in bringing genetic research to therapy. In this review, I will review, in two examples, how investigators are applying cell engineering to stem cell biology to circumvent stem cells' ethical and political constraints and bolster stem cell research and therapy.

  16. Mesenchymal Stem Cells Improve Heart Rate Variability and Baroreflex Sensitivity in Rats with Chronic Heart Failure

    Science.gov (United States)

    de Morais, Sharon Del Bem Velloso; da Silva, Luiz Eduardo Virgilio; Lataro, Renata Maria; Silva, Carlos Alberto Aguiar; de Oliveira, Luciano Fonseca Lemos; de Carvalho, Eduardo Elias Vieira; Simões, Marcus Vinicius; da Silva Meirelles, Lindolfo; Fazan, Rubens

    2015-01-01

    Heart failure induced by myocardial infarct (MI) attenuates the heart rate variability (HRV) and baroreflex sensitivity, which are important risk factors for life-threatening cardiovascular events. Therapies with mesenchymal stem cells (MSCs) have shown promising results after MI. However, the effects of MSCs on hemodynamic (heart rate and arterial pressure) variability and baroreflex sensitivity in chronic heart failure (CHF) following MI have not been evaluated thus far. Male Wistar rats received MSCs or saline solution intravenously 1 week after ligation of the left coronary artery. Control (noninfarcted) rats were also evaluated. MI size was assessed using single-photon emission computed tomography (SPECT). The left ventricular ejection fraction (LVEF) was evaluated using radionuclide ventriculography. Four weeks after MSC injection, the animals were anesthetized and instrumented for chronic ECG recording and catheters were implanted in the femoral artery to record arterial pressure. Arterial pressure and HRVs were determined in time and frequency domain (spectral analysis) while HRV was also examined using nonlinear methods: DFA (detrended fluctuation analysis) and sample entropy. The initial MI size was the same among all infarcted rats but was reduced by MSCs. CHF rats exhibited increased myocardial interstitial collagen and sample entropy combined with the attenuation of the following cardiocirculatory parameters: DFA indices, LVEF, baroreflex sensitivity, and HRV. Nevertheless, MSCs hampered all these alterations, except the LVEF reduction. Therefore, 4 weeks after MSC therapy was applied to CHF rats, MI size and myocardial interstitial fibrosis decreased, while baroreflex sensitivity and HRV improved. PMID:26059001

  17. Update on digoxin therapy in congestive heart failure.

    Science.gov (United States)

    Haji, S A; Movahed, A

    2000-07-15

    Congestive heart failure is a progressive disease with significant morbidity and mortality. Despite advances in the prevention and treatment of cardiovascular diseases, the incidence and prevalence of congestive heart failure have increased in recent years. Contributing factors include increased survival in patients with coronary artery disease (especially myocardial infarction), an aging population and significant advances in the control of other potentially lethal diseases. New and existing agents, including angiotensin-converting enzyme inhibitors, beta blockers and, more recently, spironolactone, are being used increasingly to prolong life in patients with heart failure. Although digoxin has been used to treat heart failure for more than 200 years, its role in patients with congestive heart failure and sinus rhythm is still debatable. Over the past decade, digoxin has received renewed attention because of recognition of its neurohormonal effect and the successful use of lower dosages. In recent trials, digoxin has been shown to reduce morbidity associated with congestive heart failure but to have no demonstrable effect on survival. The goal of digoxin therapy in patients with congestive heart failure is to improve quality of life by reducing symptoms and preventing hospitalizations.

  18. Skin Stem Cells in Skin Cell Therapy

    Directory of Open Access Journals (Sweden)

    Mollapour Sisakht

    2015-12-01

    Full Text Available Context Preclinical and clinical research has shown that stem cell therapy is a promising therapeutic option for many diseases. This article describes skin stem cells sources and their therapeutic applications. Evidence Acquisition Compared with conventional methods, cell therapy reduces the surgical burden for patients because it is simple and less time-consuming. Skin cell therapy has been developed for variety of diseases. By isolation of the skin stem cell from the niche, in vitro expansion and transplantation of cells offers a surprising healing capacity profile. Results Stem cells located in skin cells have shown interesting properties such as plasticity, transdifferentiation, and specificity. Mesenchymal cells of the dermis, hypodermis, and other sources are currently being investigated to promote regeneration. Conclusions Because skin stem cells are highly accessible from autologous sources and their immunological profile is unique, they are ideal for therapeutic approaches. Optimization of administrative routes requires more investigation own to the lack of a standard protocol.

  19. [Anti remodeling therapy: new strategies and future perspective in post-ischemic heart failure: Part I].

    Science.gov (United States)

    Sirico, Domenico; Salzano, Andrea; Celentani, Dario; Arcopinto, Michele; Marra, Alberto Maria; Bobbio, Emanuele; Russo, Angelo; Giallauria, Francesco; Vigorito, Carlo

    2014-12-01

    In recent years, the remarkable progress achieved in terms of survival after myocardial infarction have led to an increased incidence of chronic heart failure in survivors. This phenomenon is due to the still incomplete knowledge we possess about the complex pathophysiological mechanisms that regulate the response of cardiac tissue to ischemic injury. These involve various cell types such as fibroblasts, cells of the immune system, endothelial cells, cardiomyocytes and stem cells, as well as a myriad of mediators belonging to the system of cytokines and not only. In parallel with the latest findings on post-infarct remodeling, new potential therapeutic targets are arising to halt the progression of disease. In this review, we evaluate the results obtained from four new therapeutic strategies: in this part we evaluate gene therapy and novel aspect of stem cells therapy in remodeling; in the second part we will investigate, micro-RNA, posttranslational modification and microspheres based therapy.

  20. Stem cell therapy for diabetes

    Directory of Open Access Journals (Sweden)

    K O Lee

    2012-01-01

    Full Text Available Stem cell therapy holds immense promise for the treatment of patients with diabetes mellitus. Research on the ability of human embryonic stem cells to differentiate into islet cells has defined the developmental stages and transcription factors involved in this process. However, the clinical applications of human embryonic stem cells are limited by ethical concerns, as well as the potential for teratoma formation. As a consequence, alternative forms of stem cell therapies, such as induced pluripotent stem cells, umbilical cord stem cells and bone marrow-derived mesenchymal stem cells, have become an area of intense study. Recent advances in stem cell therapy may turn this into a realistic treatment for diabetes in the near future.

  1. Improving pacemaker therapy in congenital heart disease: contractility and resynchronization.

    Science.gov (United States)

    Karpawich, Peter P

    2015-01-01

    Designed as effective therapy for patients with symptomatic bradycardia, implantable cardiac pacemakers initially served to improve symptoms and survival. With initial applications to the elderly and those with severe myocardial disease, extended longevity was not a major concern. However, with design technology advances in leads and generators since the 1980s, pacemaker therapy is now readily applicable to all age patients, including children with congenital heart defects. As a result, emphasis and clinical interests have advanced beyond simply quantity to quality of life. Adverse cardiac effects of pacing from right ventricular apical or epicardial sites with resultant left bundle branch QRS configurations have been recognized. As a result, and with the introduction of newer catheter-delivered pacing leads, more recent studies have focused on alternative or select pacing sites such as septal, outflow tract, and para-bundle of His. This is especially important in dealing with pacemaker therapy among younger patients and those with congenital heart disease, with expected decades of artificial cardiac stimulation, in which adverse myocellular changes secondary to pacing itself have been reported. As a correlate to these alternate or select pacing sites, applications of left ventricular pacing, either via the coronary sinus, intraseptal or epicardial, alone or in combination with right ventricular pacing, have gained interest for patients with heart failure. Although cardiac resynchronization pacing has, to date, had limited clinical applications among patients with congenital heart disease, the few published reports do indicate potential benefits as a bridge to cardiac transplant. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Variabilidad de la frecuencia cardiaca y alteraciones del ritmo cardiaco asociados a la terapia con células progenitoras en enfermedad cardiovascular Heart rate variability and cardiac rhythm alterations associated with stem cell therapy in cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Carlos M Orrego

    2007-12-01

    Full Text Available Introducción: en los pacientes con falla cardiaca y cardiopatía isquémica elegibles para la terapia de células progenitoras derivadas de la médula ósea, se ha demostrado la disminución de la variabilidad de la frecuencia cardiaca [medida por la desviación estándar del intervalo RR (NN SDNN, siglas en inglés], situación que se relaciona con un aumento del riesgo cardiovascular y de eventos arrítmicos, como consecuencia de una disfunción del sistema nervioso autónomo. Métodos: se analizaron los pacientes que recibieron trasplante autólogo derivado de la médula ósea y que tenían enfermedad cardiaca isquémica aguda o crónica con fracción de eyección menor del 45%, susceptibles o no de revascularización quirúrgica y zonas de tejido miocárdico necrótico y viable. Se les realizó monitoreo Holter de 24 horas pre-trasplante, a los dos, seis y doce meses posteriores a la intervención. Resultados: se analizaron los datos de 16 pacientes, en lo referente al promedio de la frecuencia cardiaca máxima, mínima y media, la variabilidad de la frecuencia cardiaca y la aparición de arritmias ventriculares malignas. La terapia con células progenitoras derivadas de la médula ósea, se asoció con una mejoría estadísticamente significativa en la variabilidad de la frecuencia cardiaca (SDNN pasando de 65,44 ± 27 ms a 102,12 ± 37,88 ms (p= 0,004 y 100,23 ± 42,88 ms (p= 0,013 a los dos y seis meses respectivamente. En cuanto a la clasificación de riesgo cardiovascular de acuerdo con la variabilidad de la frecuencia cardiaca (SDNN, todos los pacientes considerados de alto riesgo (SDNN Introduction: in patients with chronic heart failure and ischemic cardiopathy eligible for therapy with stem cells derived from bone marrow, it has been demonstrated that there is a decrease in Heart Rate Variability (HRV, measured by the standard deviation of RR interval (NN SDNN, situation related to an increase of cardiovascular risk and arrhythmic

  3. [Routine hormonal therapy in the heart transplant donor].

    Science.gov (United States)

    Zetina-Tun, Hugo; Lezama-Urtecho, Carlos; Careaga-Reyna, Guillermo

    2016-01-01

    Successful heart transplantation depends largely on donor heart function. During brain death many hormonal changes occur. These events lead to the deterioration of the donor hearts. The 2002 Crystal Consensus advises the use of a triple hormonal scheme to rescue marginal cardiac organs. A prospective, longitudinal study was conducted on potential donor hearts during the period 1 July 2011 to 31 May 2013. All donor hearts received a dual hormonal rescue scheme, with methylprednisolone 15mg/kg IV and 200mcg levothyroxine by the enteral route. There was at least a 4 hour wait prior to the harvesting. The preload and afterload was optimised. The variables measured were: left ventricular ejection fraction cardiac graft recipient; immediate and delayed mortality. A total of 30 orthotopic heart transplants were performed, 11 female and 19 male patients, with age range between 19 and 63 years-old (Mean: 44.3, SD 12.92 years). The donor hearts were 7 female and 23 male, with age range between 15 and 45 years-old (mean 22.5, SD 7.3 years). Immediate mortality was 3.3%, 3.3% intermediate, and delayed 3.3%, with total 30 day-mortality of 10%. Month survival was 90%. The immediate graft left ventricular ejection fraction was 45%, 60% intermediate, and 68% delayed. The causes of death were: 1 primary graft dysfunction, one massive pulmonary embolism, and one due to nosocomial pneumonia. It was concluded that the use of double rescue scheme hormonal therapy is useful for the recovery and preservation of the donor hearts. This scheme improves survival within the first 30 days after transplantation. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  4. Endogenous cardiac stem cells for the treatment of heart failure

    Directory of Open Access Journals (Sweden)

    Fuentes T

    2013-03-01

    Full Text Available Tania Fuentes, Mary Kearns-Jonker Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, CA, USA Abstract: Stem cell-based therapies hold promise for regenerating the myocardium after injury. Recent data obtained from phase I clinical trials using endogenous cardiovascular progenitors isolated directly from the heart suggest that cell-based treatment for heart patients using stem cells that reside in the heart provides significant functional benefit and an improvement in patient outcome. Methods to achieve improved engraftment and regeneration may extend this therapeutic benefit. Endogenous cardiovascular progenitors have been tested extensively in small animals to identify cells that improve cardiac function after myocardial infarction. However, the relative lack of large animal models impedes translation into clinical practice. This review will exclusively focus on the latest research pertaining to humans and large animals, including both endogenous and induced sources of cardiovascular progenitors. Keywords: Isl1, iPSC, large animal, c-kit, cardiosphere

  5. System overview of the fully implantable destination therapy--ReinHeart-total artificial heart.

    Science.gov (United States)

    Pelletier, Benedikt; Spiliopoulos, Sotirios; Finocchiaro, Thomas; Graef, Felix; Kuipers, Kristin; Laumen, Marco; Guersoy, Dilek; Steinseifer, Ulrich; Koerfer, Reiner; Tenderich, Gero

    2015-01-01

    Owing to the lack of suitable allografts, the demand for long-term mechanical circulatory support in patients with biventricular end-stage heart failure is rising. Currently available Total Artificial Heart (TAH) systems consist of pump units with only limited durability, percutaneous tubes and bulky external equipment that limit the quality of life. Therefore we are focusing on the development of a fully implantable, highly durable destination therapy total artificial heart. The ReinHeart-TAH system consists of a passively filling pump unit driven by a low-wear linear drive between two artificial ventricles, an implantable control unit and a compliance chamber. The TAH is powered by a transcutaneous energy transmission system. The flow distribution inside the ventricles was analysed by fluid structure interaction simulation and particle image velocimetry measurements. Along with durability tests, the hydrodynamic performance and flow balance capability were evaluated in a mock circulation loop. Animal trials are ongoing. Based on fluid structure interaction simulation and particle image velocimetry, blood stagnation areas have been significantly reduced. In the mock circulation loop the ReinHeart-TAH generated a cardiac output of 5 l/min at an operating frequency of 120 bpm and an aortic pressure of 120/80 mmHg. The highly effective preload sensitivity of the passively filling ventricles allowed the sensorless integration of the Frank Starling mechanism. The ReinHeart-TAH effectively replaced the native heart's function in animals for up to 2 days. In vitro and in vivo testing showed a safe and effective function of the ReinHeart-TAH system. This has the potential to become an alternative to transplantation. However, before a first-in-man implant, chronic animal trials still have to be completed. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  6. Influence of diuretic therapy on the features of heart rhythm variability changes in chronic heart failure patients

    Directory of Open Access Journals (Sweden)

    K R Alyeva

    2018-02-01

    Full Text Available Aim. To study comparative influence of furosemide and torasemide on heart rhythm variability in patients with chronic heart failure of ischemic origin. Methods. The study included 48 patients (29 males and 19 females with ischemic heart disease complicated by chronic heart failure, NYHA functional classes II-IV. All patients were randomized into two groups: group 1 (25 patients received furosemide as diuretic therapy, and group 2 (23 patients received torasemide. All patient underwent clinical examination including assessment of complaints and physical examination, laboratory and instrumental tests (electrocardiography, echocardiography, 6-minute walk test, 24 Hour Holter ECG monitoring before and 30 days after starting diuretic therapy. Results. Against the background of one-month diuretic therapy, positive dynamics of clinical parameters was registered in both main groups of patients receiving both furosemide and torasemide. In furosemide group deterioration of heart rhythm variability was observed. Torasemide treatment resulted in considerable improvement of vegetative regulation of heart activity. Conclusion. Diuretic therapy with furosemide is characterized by changes of time and spectral parameters of vegetative regulation of heart rhythm towards strengthening of sympathetic and attenuation of parasympathetic influence; diuretic therapy with torasemide resulted in considerable improvement of heart rhythm variability parameters, attenuation of sympathetic and strengthening of parasympathetic influence on heart rhythm that provides additional cardioprotection in the treatment of patients with chronic heart failure of ischemic origin.

  7. Influence of diuretic therapy on the features of heart rhythm variability changes in chronic heart failure patients

    OpenAIRE

    K R Alyeva; A B Bakhshaliev; S M Kakhramanova

    2018-01-01

    Aim. To study comparative influence of furosemide and torasemide on heart rhythm variability in patients with chronic heart failure of ischemic origin. Methods. The study included 48 patients (29 males and 19 females) with ischemic heart disease complicated by chronic heart failure, NYHA functional classes II-IV. All patients were randomized into two groups: group 1 (25 patients) received furosemide as diuretic therapy, and group 2 (23 patients) received torasemide. All patient underwen...

  8. Inflammation, cytokines and anti-inflammatory therapies in heart failure.

    Science.gov (United States)

    Tabet, J Y; Lopes, M E; Champagne, S; Su, J B; Merlet, P; Hittinger, L

    2002-03-01

    Both experimental and clinical studies have shown a role for inflammation in the pathogenesis of heart failure. This seems related to an imbalance between pro-inflammatory and anti-inflammatory cytokines. Certain categories in patients with dilated cardiomyopathy have shown the presence of humoral and cellular immunity activation suggesting a possible relation between myocarditis and dilated cardiomyopathy. Recent studies suggest a link between the circulating levels of cytokines (TNF alpha IL-1 et IL-6), the clinical status and prognostic. However, the mechanisms connecting heart failure and cytokine activation are unclear and the sites of cytokines production remain controversial. In the clinical setting, specific measurements of cytokines are not available. As tests of inflammation, erythrocyte sedimentation rate and C-reactive protein concentration appear to have interesting pronostic values. Current conventional therapy i.e. ACE inhibitors, type I angiotensin II antagonist and beta-blockers have shown some anti-cytokine properties. Recently, immunosuppressive therapies have shown their ability to improve symptoms and LV ejection in selected patients with dilated cardiomyopathy and clear sign of myocardium inflammation. Specific anti-cytokine therapy have been developed and showed interesting results in preliminary clinical studies. However large clinical trials testing this new therapy have been stoppel prematurely because of deterious effects.

  9. American Society of Gene & Cell Therapy

    Science.gov (United States)

    ... Chicago Learn More Close The American Society of Gene & Cell Therapy ASGCT is the primary membership organization for scientists, ... Therapeutics Official Journal of the American Society of Gene & Cell Therapy Molecular Therapy is the leading journal for gene ...

  10. "Nihilism" of chronic heart failure therapy in children and why effective therapy is withheld.

    Science.gov (United States)

    Schranz, Dietmar; Voelkel, Norbert F

    2016-04-01

    Major advances in chronic heart failure (cHF) therapy have been achieved and documented in adult patients, while research regarding the mechanisms and therapy of cHF in children has lagged behind. Based on receptor physiological studies and pharmacological knowledge, treatment with specific ß1-adrenergic receptor blocker (ARB), tissue angiotensin-converting enzyme inhibitor (ACE-I), and mineralocorticoid antagonists have to be recommended in children despite lack of sufficient data derived from prospective randomized studies. At our institution, bisoprolol, lisinopril, and spironolactone have been firmly established to treat systolic cHF, hypoplastic left heart syndrome (HLHS) following hybrid approach and congenital left-right shunt diseases, latest in patients where surgery has to be delayed. Chronic therapy with long-acting diuretics and fluid restriction are not advocated because short-term effects are achieved at the expense of further neuro-humoral stimulation. It remains unclear why diuretics are recommended although evidence-based studies, documenting long-term benefit, are missing. However, that is true for all currently used drugs for pediatric cHF. This review focuses on the prevailing "nihilism" of cHF therapy in children with the goal to encourage physicians to treat pediatric cHF with a rationally designed therapy, which combines available agents that have been shown to improve survival in adult patients with cHF. Because of the lack of clinical trials, which generate the needed evidence, surrogate variables like heart and respiratory rate, weight gain, image-derived data, and biomarkers should be monitored and used instead. The recommended pharmacological therapy for systolic heart failure is also provided as the basis for utilizing reversible pulmonary arterial banding (PAB) as a novel strategy in young children with dilative cardiomyopathy (DCM) with preserved right ventricular function. • Heart failure (HF) in children is a serious public

  11. Amyloid heart disease: genetics translated into disease-modifying therapy.

    Science.gov (United States)

    Sperry, Brett W; Tang, W H Wilson

    2017-06-01

    Given increased awareness and improved non-invasive diagnostic tools, cardiac amyloidosis has become an increasingly recognised aetiology of increased ventricular wall thickness and heart failure with preserved ejection fraction. Once considered a rare disease with no treatment options, translational research has harnessed novel pathways and led the way to promising treatment options. Gene variants that contribute to amyloid heart disease provide unique opportunities to explore potential disease-modifying therapeutic strategies. Amyloidosis has become the model disease through which gene therapy using small interfering RNAs and antisense oligonucleotides has evolved. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Trimetazidine therapy for diabetic mouse hearts subjected to ex vivo acute heart failure.

    Science.gov (United States)

    Breedt, Emilene; Lacerda, Lydia; Essop, M Faadiel

    2017-01-01

    Acute heart failure (AHF) is the most common primary diagnosis for hospitalized heart diseases in Africa. As increased fatty acid β-oxidation (FAO) during heart failure triggers detrimental effects on the myocardium, we hypothesized that trimetazidine (TMZ) (partial FAO inhibitor) offers cardioprotection under normal and obese-related diabetic conditions. Hearts were isolated from 12-14-week-old obese male and female diabetic (db/db) mice versus lean non-diabetic littermates (db/+) controls. The Langendorff retrograde isolated heart perfusion system was employed to establish an ex vivo AHF model: a) Stabilization phase-Krebs Henseleit buffer (10 mM glucose) at 100 mmHg (25 min); b) Critical Acute Heart Failure (CAHF) phase-(1.2 mM palmitic acid, 2.5 mM glucose) at 20 mmHg (25 min); and c) Recovery Acute Heart Failure phase (RAHF)-(1.2 mM palmitic acid, 10 mM glucose) at 100 mmHg (25 min). Treated groups received 5 μM TMZ in the perfusate during either the CAHF or RAHF stage for the full duration of each respective phase. Both lean and obese males benefited from TMZ treatment administered during the RAHF phase. Sex differences were observed only in lean groups where the phases of the estrous cycle influenced therapy; only the lean follicular female group responded to TMZ treatment during the CAHF phase. Lean luteal females rather displayed an inherent cardioprotection (without treatments) that was lost with obesity. However, TMZ treatment initiated during RAHF was beneficial for obese luteal females. TMZ treatment triggered significant recovery for male and obese female hearts when administered during RAHF. There were no differences between lean and obese male hearts, while lean females displayed a functional recovery advantage over lean males. Thus TMZ emerges as a worthy therapeutic target to consider for AHF treatment in normal and obese-diabetic individuals (for both sexes), but only when administered during the recovery phase and not during the very acute

  13. Stem cell therapy for inflammatory bowel disease

    NARCIS (Netherlands)

    Duijvestein, Marjolijn

    2012-01-01

    Hematopoietic stem cell transplantation (HSCT) and mesenchymal stromal (MSC) cell therapy are currently under investigation as novel therapies for inflammatory bowel diseases (IBD). Hematopoietic stem cells are thought to repopulate the immune system and reset the immunological response to luminal

  14. Stem Cell Therapy in Treatment of Different Diseases

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Sahraian

    2012-02-01

    Full Text Available Stem cells are undifferentiated cells with the ability of proliferation, regeneration, conversion to differentiated cells and producing various tissues. Stem cells are divided into two categories of embryonic and adult. In another categorization stem cells are divided to Totipotent, Multipotent and Unipotent cells.So far usage of stem cells in treatment of various blood diseases has been studied (such as lymphoblastic leukemia, myeloid leukemia, thalassemia, multiple myeloma and cycle cell anemia. In this paper the goal is evaluation of cell therapy in treatment of Parkinsons disease, Amyotrophic lateral sclerosis, Alzheimer, Stroke, Spinal Cord Injury, Multiple Sclerosis, Radiation Induced Intestinal Injury, Inflammatory Bowel Disease, Liver Disease, Duchenne Muscular Dystrophy, Diabetes, Heart Disease, Bone Disease, Renal Disease, Chronic Wounds, Graft-Versus-Host Disease, Sepsis and Respiratory diseases. It should be mentioned that some disease that are the target of cell therapy are discussed in this article.

  15. Thioredoxin-1 (Trx1) engineered mesenchymal stem cell therapy increased pro-angiogenic factors, reduced fibrosis and improved heart function in the infarcted rat myocardium.

    Science.gov (United States)

    Suresh, Sumanth C; Selvaraju, Vaithinathan; Thirunavukkarasu, Mahesh; Goldman, Joshua W; Husain, Aaftab; Alexander Palesty, J; Sanchez, Juan A; McFadden, David W; Maulik, Nilanjana

    2015-12-15

    Engraftment of mesenchymal stem cells (MSCs) has emerged as a powerful candidate for mediating myocardial repair. In this study, we genetically modified MSCs with an adenovector encoding thioredoxin-1 (Ad.Trx1). Trx1 has been described as a growth regulator, a transcription factor regulator, a cofactor, and a powerful antioxidant. We explored whether engineered MSCs, when transplanted, are capable of improving cardiac function and angiogenesis in a rat model of myocardial infarction (MI). Rat MSCs were cultured and divided into MSC, MSC+Ad.LacZ, and MSC+Ad.Trx1 groups. The cells were assayed for proliferation, and differentiation potential. In addition, rats were divided into control-sham (CS), control-MI (CMI), MSC+Ad.LacZ-MI (MLZMI), and MSC+Ad.Trx1-MI (MTrxMI) groups. MI was induced by left anterior descending coronary artery (LAD) ligation, and MSCs preconditioned with either Ad.LacZ or Ad.Trx1 were immediately administered to four sites in the peri-infarct zone. The MSC+Ad.Trx1 cells increased the proliferation capacity and maintained pluripotency, allowing them to divide into cardiomyocytes, smooth muscle, and endothelial cells. Western blot analysis, 4 days after treatment showed increased vascular endothelial growth factor (VEGF), heme oxygenase-1 (HO-1), and C-X-C chemokine receptor type 4 (CXCR4). Also capillary density along with myocardial function as examined by echocardiography was found to be increased. Fibrosis was reduced in the MTrxMI group compared to MLZMI and CMI. Visualization of Connexin-43 by immunohistochemistry confirmed increased intercellular connections in the MTrxMI rats compared to MLZMI. Engineering MSCs to express Trx1 may prove to be a strategic therapeutic modality in the treatment of cardiac failure. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Combined aquaretic and diuretic therapy in acute heart failure

    Directory of Open Access Journals (Sweden)

    Goyfman M

    2017-06-01

    Full Text Available Michael Goyfman,1 Paul Zamudio,2 Kristine Jang,3 Jennifer Chee,3 Catherine Miranda,2 Javed Butler,1 Nand K Wadhwa2 1Division of Cardiology, 2Division of Nephrology, 3Department of Medicine, Stony Brook School of Medicine, Stony Brook, NY, USA Introduction: Acute heart failure (AHF is a leading cause of hospitalization and readmission in the US. The present study evaluated maximum diuresis while minimizing electrolyte imbalances, hemodynamic instability, and kidney dysfunction, to achieve a euvolemic state safely in a shorter period of time.Methods and results: A protocol of combined therapy with furosemide, metolazone, and spironolactone, with or without tolvaptan and acetazolamide, was used in 17 hospitalized patients with AHF. The mean number of days on combination diuretic protocol was 3.8 days. The mean daily fluid balance was 3.0±2.1 L negative. The mean daily urine output (UOP was 4.1±2.0 L (range 1.8–10.5 L. There were minimal fluctuations in serum electrolyte levels and serum creatinine over the duration of diuretic therapy. There was no statistically significant change in patients’ creatinine from immediately prior to therapy to the last day of therapy, with a mean increase in creatinine of 0.14 mg/dL (95% CI −0.03, +0.30, p=0.10.Conclusion: Our strategy of treating AHF by achieving high UOP, while maintaining stable electrolytes and creatinine in a short period to euvolemic state, is safe. Keywords: diuretics, aquaretic, acute heart failure, volume overload

  17. Protein Kinases as Drug Development Targets for Heart Disease Therapy

    Directory of Open Access Journals (Sweden)

    Alison L. Müller

    2010-07-01

    Full Text Available Protein kinases are intimately integrated in different signal transduction pathways for the regulation of cardiac function in both health and disease. Protein kinase A (PKA, Ca2+-calmodulin-dependent protein kinase (CaMK, protein kinase C (PKC, phosphoinositide 3-kinase (PI3K and mitogen-activated protein kinase (MAPK are not only involved in the control of subcellular activities for maintaining cardiac function, but also participate in the development of cardiac dysfunction in cardiac hypertrophy, diabetic cardiomyopathy, myocardial infarction, and heart failure. Although all these kinases serve as signal transducing proteins by phosphorylating different sites in cardiomyocytes, some of their effects are cardioprotective whereas others are detrimental. Such opposing effects of each signal transduction pathway seem to depend upon the duration and intensity of stimulus as well as the type of kinase isoform for each kinase. In view of the fact that most of these kinases are activated in heart disease and their inhibition has been shown to improve cardiac function, it is suggested that these kinases form excellent targets for drug development for therapy of heart disease.

  18. Bridge Therapy Outcomes in Patients With Mechanical Heart Valves.

    Science.gov (United States)

    Delate, Thomas; Meisinger, Stephanie M; Witt, Daniel M; Jenkins, Daniel; Douketis, James D; Clark, Nathan P

    2017-11-01

    Bridge therapy is associated with an increased risk of major bleeding in patients with atrial fibrillation and venous thromboembolism (TE) without a corresponding reduction in TE. The benefits of bridge therapy in patients with mechanical heart valve (MHV) prostheses interrupting warfarin for invasive procedures are not well described. A retrospective cohort study was conducted at an integrated health-care delivery system. Anticoagulated patients with MHV interrupting warfarin for invasive diagnostic or surgical procedures between January 1, 2006, and March 31, 2012, were identified. Patients were categorized according to exposure to bridge therapy during the periprocedural period and TE risk (low, medium, and high). Outcomes validated via manual chart review included clinically relevant bleeding, TE, and all-cause mortality in the 30 days following the procedure. There were 547 procedures in 355 patients meeting inclusion criteria. Mean cohort age was 65.2 years, and 38% were female. Bridge therapy was utilized in 466 (85.2%) procedures (95.2%, 77.3%, and 65.8% of high, medium, and low TE risk category procedures, respectively). The 30-day rate of clinically relevant bleeding was numerically higher in bridged (5.8%; 95% confidence interval [CI], 3.9%-8.3%) versus not bridged procedures (1.2%; 95% CI, <0.1%-6.7%; P = .102). No TEs or deaths were identified. The use of bridge therapy is common among patients with MHV and may be associated with increased bleeding risk. Further research is needed to determine whether bridge therapy reduces TE in patients with MHV interrupting warfarin for invasive procedures.

  19. Cell Therapies in Cardiomyopathy: Current Status of Clinical Trials

    Directory of Open Access Journals (Sweden)

    Ming Hao

    2017-01-01

    Full Text Available Because the human heart has limited potential for regeneration, the loss of cardiomyocytes during cardiac myopathy and ischaemic injury can result in heart failure and death. Stem cell therapy has emerged as a promising strategy for the treatment of dead myocardium, directly or indirectly, and seems to offer functional benefits to patients. The ideal candidate donor cell for myocardial reconstitution is a stem-like cell that can be easily obtained, has a robust proliferation capacity and a low risk of tumour formation and immune rejection, differentiates into functionally normal cardiomyocytes, and is suitable for minimally invasive clinical transplantation. The ultimate goal of cardiac repair is to regenerate functionally viable myocardium after myocardial infarction (MI to prevent or heal heart failure. This review provides a comprehensive overview of treatment with stem-like cells in preclinical and clinical studies to assess the feasibility and efficacy of this novel therapeutic strategy in ischaemic cardiomyopathy.

  20. Effect of Cardiac Resynchronization Therapy on Inflammation in Congestive Heart Failure: A Review.

    Science.gov (United States)

    Lappegård, K T; Bjørnstad, H; Mollnes, T E; Hovland, A

    2015-09-01

    Congestive heart failure is associated with increased levels of several inflammatory mediators, and animal studies have shown that infusion of a number of cytokines can induce heart failure. However, several drugs with proven efficacy in heart failure have failed to affect inflammatory mediators, and anti-inflammatory therapy in heart failure patients has thus far been disappointing. Hence, to what extent heart failure is caused by or responsible for the increased inflammatory burden in the patient is still unclear. Over the past couple of decades, resynchronization therapy with a biventricular pacemaker has emerged as an effective treatment in a subset of heart failure patients, reducing both morbidity and mortality. Such treatment has also been shown to affect the inflammation associated with heart failure. In this study, we review recent data on the association between heart failure and inflammation, and in particular how resynchronization therapy can affect the inflammatory process. © 2015 The Foundation for the Scandinavian Journal of Immunology.

  1. Stem Cells for Cardiac Regeneration by Cell Therapy and Myocardial Tissue Engineering

    Science.gov (United States)

    Wu, Jun; Zeng, Faquan; Weisel, Richard D.; Li, Ren-Ke

    Congestive heart failure, which often occurs progressively following a myocardial infarction, is characterized by impaired myocardial perfusion, ventricular dilatation, and cardiac dysfunction. Novel treatments are required to reverse these effects - especially in older patients whose endogenous regenerative responses to currently available therapies are limited by age. This review explores the current state of research for two related approaches to cardiac regeneration: cell therapy and tissue engineering. First, to evaluate cell therapy, we review the effectiveness of various cell types for their ability to limit ventricular dilatation and promote functional recovery following implantation into a damaged heart. Next, to assess tissue engineering, we discuss the characteristics of several biomaterials for their potential to physically support the infarcted myocardium and promote implanted cell survival following cardiac injury. Finally, looking ahead, we present recent findings suggesting that hybrid constructs combining a biomaterial with stem and supporting cells may be the most effective approaches to cardiac regeneration.

  2. The Current and Future Landscape of SERCA Gene Therapy for Heart Failure: A Clinical Perspective.

    Science.gov (United States)

    Hayward, Carl; Banner, Nicholas R; Morley-Smith, Andrew; Lyon, Alexander R; Harding, Sian E

    2015-05-01

    Gene therapy has been applied to cardiovascular disease for over 20 years but it is the application to heart failure that has generated recent interest in clinical trials. There is laboratory and early clinical evidence that delivery of sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) gene therapy is beneficial for heart failure and this therapy could become the first positive inotrope with anti-arrhythmic properties. In this review we will discuss the rationale for SERCA2a gene therapy as a viable strategy in heart failure, review the published data, and discuss the ongoing clinical trials, before concluding with comments on the future challenges and potential for this therapy.

  3. VASCULAR REMODELING AND HEART RATE VARIABILITY IN DIFFERENT ANTIHYPERTENSIVE THERAPIES

    Directory of Open Access Journals (Sweden)

    E. D. Golovanova

    2008-01-01

    Full Text Available Aim. To study the effect of the long-term antihypertensive monotherapy with indapamide (Arifon Retard, 1,5 mg/d, metoprolol tartrate (Egilok Retard, 50 mg/d and combined therapy with indapamide and perindopril (Noliprel Forte, 1 tab/d: perindopril 4 mg and indapamide 1,25 mg on pulse wave velocity (PWV, cardio-ankle vascular index (CAVI and the sympathetic system activity.Material and methods. 88 patients, aged 30-59 y.o. (32 normotensive patients, 56 with arterial hypertension [HT] of 1-2 grades were examined. Biological age (BA was determined by the linear regression and the vascular wall age (VWA was estimated with the use of volume sphygmography (“VaSera-1000”, “Fucuda Denshi”, Japan. 39 patients with HT were randomized into 3 parallel groups with studied therapies lasted for 6 months. PWV, CAVI of the vessels of elastic, muscular and mixed types, blood pressure, measured in upper and lower extremities and heart rate variability (HRV were determined before and at the end of the therapies.Results. BA and VWA were elevated in all of patients with HT as compared with normotensive patients. The reduction in PWV and CAVI of the vessels of elastic and mixed types, HRV increase were found in patients with Arifon Retard monotherapy. Monotherapy with metoprolol significantly improved HVR without any influence on the vascular remodeling. Noliprel Forte significantly decreased in blood pressure in the upper and lower extremities, PWV and CAVI of the vessels of all types, decreased in VWA and increased in parasympathetic drive.Conclusion. Long-term therapy with Arifon Retard and Noliprel Forte resulted in decrease in vascular remodeling and increase in HRV simultaneously with significant antihypertensive effect in patients with HT. Metoprolol low doses therapy resulted in normalization of autonomic drive independently on antihypertensive action.

  4. Music therapy can lower the heart rates of severely sick children.

    Science.gov (United States)

    Uggla, L; Bonde, L O; Svahn, B M; Remberger, M; Wrangsjö, B; Gustafsson, B

    2016-10-01

    Paediatric recipients of haematopoietic stem cell transplants (HSCT) are at increased risk of developing post-traumatic stress disorder (PTSD), and there is a need to identify interventions that can alleviate stress in this group. The aim of this study was to examine the previously unexplored effect of music therapy on children undergoing HSCT, by analysing physiological parameters and comparing them with a control group. We performed a randomised clinical pilot study of 24 patients up to the age of 16 undergoing HSCT at Karolinska University Hospital, Huddinge, Sweden. Music therapy, including expressive and receptive elements, was performed twice a week in the treatment group and compared to standard care in the control group. Physiological parameters were evaluated according to the hospital's protocols. The music therapy group had significantly reduced evening heart rates compared to the control group (p Music therapy significantly lowered the heart rate of children undergoing HSCT for at least four to eight hours, indicating reduced stress levels and potentially lowering the risk of developing PTSD. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  5. [Elderly heart failure patients and the role of beta-blocker therapy

    NARCIS (Netherlands)

    Middeljans-Tijssen, C.W.; Jansen, R.W.M.M.

    2006-01-01

    In this article different aspects of chronic heart failure in old age are described. We mainly focus on the place of beta-blocker therapy in chronic heart failure. Beta-blockers are recommended for the treatment of stable chronic heart failure with left ventricular systolic dysfunction. There is

  6. [Cell therapy for type I diabete].

    Science.gov (United States)

    Sokolova, I B

    2009-01-01

    Cell therapy is a modern and promising approach to type I diabetes mellitus treatment. Nowadays a wide range of cells is used in laboratory experiments and clinical studies, including allogeneic and xenogeneic cells of Langergance islets, bone marrow cells, haematopoietic stem cells, mesenchymal stem cells, and cord blood stem cells. Any type of the cells named could correct the status of the patients to a certain extent. However, full recovery after cell therapy has not been achieved yet.

  7. Cardiac tissue engineering and regeneration using cell-based therapy

    Directory of Open Access Journals (Sweden)

    Alrefai MT

    2015-05-01

    Full Text Available Mohammad T Alrefai,1–3 Divya Murali,4 Arghya Paul,4 Khalid M Ridwan,1,2 John M Connell,1,2 Dominique Shum-Tim1,2 1Division of Cardiac Surgery, 2Division of Surgical Research, McGill University Health Center, Montreal, QC, Canada; 3King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia; 4Department of Chemical and Petroleum Engineering, School of Engineering, University of Kansas, Lawrence, KS, USA Abstract: Stem cell therapy and tissue engineering represent a forefront of current research in the treatment of heart disease. With these technologies, advancements are being made into therapies for acute ischemic myocardial injury and chronic, otherwise nonreversible, myocardial failure. The current clinical management of cardiac ischemia deals with reestablishing perfusion to the heart but not dealing with the irreversible damage caused by the occlusion or stenosis of the supplying vessels. The applications of these new technologies are not yet fully established as part of the management of cardiac diseases but will become so in the near future. The discussion presented here reviews some of the pioneering works at this new frontier. Key results of allogeneic and autologous stem cell trials are presented, including the use of embryonic, bone marrow-derived, adipose-derived, and resident cardiac stem cells. Keywords: stem cells, cardiomyocytes, cardiac surgery, heart failure, myocardial ischemia, heart, scaffolds, organoids, cell sheet and tissue engineering

  8. Relation between hormone replacement therapy and ischaemic heart disease in women

    DEFF Research Database (Denmark)

    Løkkegaard, E; Pedersen, A T; Heitmann, B L

    2003-01-01

    To investigate the risk of ischaemic heart disease and myocardial infarction among women using hormone replacement therapy, especially the potential modifying effect of cardiovascular risk factors.......To investigate the risk of ischaemic heart disease and myocardial infarction among women using hormone replacement therapy, especially the potential modifying effect of cardiovascular risk factors....

  9. [High-dosage glucocorticoid therapy in acute heart infarct and in cardiogenic shock].

    Science.gov (United States)

    Krosch, H; Schäbitz, J

    1977-11-15

    40 patients with cardiogenic shock in consequence of contractility insufficiency of the heart were treated with high doses of prednisolon for short time. In 10 cases a good result of the treatment was to be seen so that the lethality quota was smaller than that of a reference group of the same age. The pharmacodynamic effect is seen in an improvement of the micro-circulation by a peripheric vasodilatation. 10 patients with acute myocardial infarction got a therapy with glucocorticoid combined with a treatment with anti-coagulants during the first both weeks. In this connection modern experimental examinations of animals are discussed which showed that glucocorticoides improve the anoxy tolerance of the heart muscle cell.

  10. A first step beyond traditional boundaries: destination therapy with the SynCardia total artificial heart.

    Science.gov (United States)

    Spiliopoulos, Sotirios; Koerfer, Reiner; Tenderich, Gero

    2014-06-01

    The SynCardia total artificial heart is currently used as a bridge to transplantation therapy in cases of irreversible, acute or chronic, biventricular heart failure. We describe the implementation of this technology in the context of destination therapy in a patient with an end-stage heart failure on grounds of primary amyloidosis. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  11. Regenerative medicine and cell therapy

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2013-06-01

    Full Text Available Cell therapies are clinical practices already by decades in fields like blood tumors and severe burns but the term itself when associated with regenerative medicine switch on a cascade of imaginery thoughts that risk to create false hopes; in other words, the imaginary idea that physicians can cure all of the diseases since each day the media report of some very important advance in stem cell biology. This is a mistake, mirrored by the downbeat idea that speculators are pledging false possibilities selling illusions of miracle cures...

  12. Repair of ischemic heart disease with novel bone marrow-derived multipotent stem cells.

    Science.gov (United States)

    Lee, Namho; Thorne, Tina; Losordo, Douglas W; Yoon, Young-sup

    2005-07-01

    Congestive heart failure is a growing, worldwide epidemic. The major causes of heart failure are related to irreversible damage resulting from myocardial infarction (heart attack). The long-standing axiom has been that the myocardium has a limited capacity for self-repair or regeneration; and the irreversible loss of cardiac muscle and accompanying contraction and fibrosis of myocardial scar tissue, sets into play a series of events, namely, progressive ventricular remodeling of nonischemic myocardium that ultimately leads to progressive heart failure. The loss of cardiomyocyte survival cues is associated with diverse pathways for heart failure, underscoring the importance of maintaining the number of viable cardiomyocytes during heart failure progression. Currently, no medication or procedure used clinically has shown efficacy in replacing the myocardial scar with functioning contractile tissue. Therefore, given the major morbidity and mortality associated with myocardial infarction and heart failure, new approaches have been sought to address the principal pathophysiologic deficits responsible for these conditions, resulting from the loss of cardiomyocytes and viable blood vessels. Recently, the identification of stem cells from bone marrow capable of contributing to tissue regeneration has ignited significant interest in the possibility that cell therapy could be employed therapeutically for the repair of damaged myocardium. In this review, we will discuss the currently available bone marrow-derived stem progenitor cells for myocardial repair and focus on the advantages of using recently identified novel bone marrow-derived multipotent stem cells (BMSC).

  13. [Alternatives to conventional diuretic therapy in heart failure].

    Science.gov (United States)

    Morales-Rull, José Luis; Trullàs, Joan Carles; Formiga, Francesc

    2014-03-01

    Although treatment of acute heart failure is based primarily on the administration of intravenous loop diuretics, evidence supporting this practice is still scarce and there is uncertainty about the optimal dose. The existence of a considerable percentage of patients refractory to diuretic therapy and worsening of renal failure associated with the use of these drugs, with possible implications for medium-term mortality, have prompted the search for more effective and safer alternatives. Extracorporeal purification techniques, such as ultrafiltration, have demonstrated efficacy, although their superiority is unclear, due to the possible adverse effects associated with the procedure. The use of low-dose dopamine is not superior to conventional diuretic therapy after the first few hours of treatment. Moreover, combination with furosemide and hypertonic saline could be a valid alternative for patients with refractory congestion and depressed ejection fraction and serum creatinine ≤ 2.5mg/dL, but further studies are needed before its widespread use. The use of tolvaptan may be an effective alternative in the short-term but its use may be limited by its price. There is still controversy about whether treatment with loop diuretics is associated with higher mortality in all groups of patients with HF exacerbations. These controversies should be clarified by future clinical trials. Copyright © 2014 Elsevier España, S.L. All rights reserved.

  14. Immunosuppressive T-cell antibody induction for heart transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Møller, Christian H; Gustafsson, Finn

    2013-01-01

    Heart transplantation has become a valuable and well-accepted treatment option for end-stage heart failure. Rejection of the transplanted heart by the recipient's body is a risk to the success of the procedure, and life-long immunosuppression is necessary to avoid this. Clear evidence is required...... to identify the best, safest and most effective immunosuppressive treatment strategy for heart transplant recipients. To date, there is no consensus on the use of immunosuppressive antibodies against T-cells for induction after heart transplantation....

  15. Stem-cell therapy for neurologic diseases

    Directory of Open Access Journals (Sweden)

    Shilpa Sharma

    2015-01-01

    Full Text Available With the advent of research on stem cell therapy for various diseases, an important need was felt in the field of neurological diseases. While congenital lesion may not be amenable to stem cell therapy completely, there is a scope of partial improvement in the lesions and halt in further progression. Neuro degenerative lesions like Parkinson′s disease, multiple sclerosis and amyotrophic lateral sclerosis have shown improvement with stem cell therapy. This article reviews the available literature and summarizes the current evidence in the various neurologic diseases amenable to stem cell therapy, the plausible mechanism of action, ethical concerns with insights into the future of stem cell therapy.

  16. Can stem cells really regenerate the human heart? Use your noggin, dickkopf! Lessons from developmental biology.

    Science.gov (United States)

    Sommer, Paula

    2013-06-01

    The human heart is the first organ to develop and its development is fairly well characterised. In theory, the heart has the capacity to regenerate, as its cardiomyocytes may be capable of cell division and the adult heart contains a cardiac stem cell niche, presumably capable of differentiating into cardiomyocytes and other cardiac-associated cell types. However, as with most other organs, these mechanisms are not activated upon serious injury. Several experimental options to induce regeneration of the damaged heart tissue are available: activate the endogenous cardiomyocytes to divide, coax the endogenous population of stem cells to divide and differentiate, or add exogenous cell-based therapy to replace the lost cardiac tissue. This review is a summary of the recent research into all these avenues, discussing the reasons for the limited successes of clinical trials using stem cells after cardiac injury and explaining new advances in basic science. It concludes with a reiteration that chances of successful regeneration would be improved by understanding and implementing the basics of heart development and stem cell biology.

  17. Haemodynamic unloading increases the survival and affects the differentiation of cardiac stem cells after implantation into an infarcted heart.

    Science.gov (United States)

    Kurazumi, Hiroshi; Li, Tao-Sheng; Takemoto, Yoshihiro; Suzuki, Ryo; Mikamo, Akihito; Guo, Chang-Ying; Murata, Tomoaki; Hamano, Kimikazu

    2014-06-01

    It has been anticipated that stem cell therapy is capable of repairing an injured heart but is currently limited by its marginal efficacy. We believe that mechanical stress due to haemodynamic loading may negate the therapeutic potency of stem cells and therefore investigated how haemodynamic unloading affects the survival and differentiation of stem cells after implantation into an infarcted heart. A left ventricular (LV) haemodynamic unloading model was implemented by heterotopic transplantation of an infarcted donor heart into another healthy mouse. An in situ infarcted heart with general haemodynamic loading was used as control. A total of 5 million cardiac stem cells expanded from green fluorescence protein (GFP)-transgenic mouse were intramyocardially implanted into the infarcted LVs of haemodynamically unloaded donor heart or general haemodynamic loaded heart. The survival and differentiation of the implanted cardiac stem cells were evaluated by histological analyses at 3 and 21 days after cell implantation (n = 5-6 in each time points per group). Compared with the general haemodynamic loading condition, haemodynamic unloading of the infarcted hearts significantly improved the survival, increased the proliferation and inhibited the apoptosis of cardiac stem cells at 21 days after cell implantation (P cells was much higher in the unloaded hearts than in the loaded hearts at 21 days after cell implantation, although the difference was not statistically significant (5.67 ± 5.10 vs 0.75 ± 0.50, P = 0.051). Among the surviving GFP(+) donor cells 21 days after implantation, the expressions of platelet endothelial cell adhesion molecule-1, smooth muscle actin and sarcomeric alpha actin were ~7, 38 and 27% in the loaded heart and ~19, 14 and 55% in the unloaded heart, respectively. Haemodynamic unloading favours the survival/engraftment of donor stem cells and affects their differentiation after implantation into an infarcted heart. Although further studies in a

  18. Eurythmy therapy increases specific oscillations of heart rate variability.

    Science.gov (United States)

    Edelhäuser, Friedrich; Minnerop, Antje; Trapp, Barbara; Büssing, Arndt; Cysarz, Dirk

    2015-06-06

    Mind-body therapies are beneficial for several diseases (e.g. chronic pain, arterial hypertension, mood disorders). Eurythmy therapy (EYT) is a mind-body therapy from Anthroposophic Medicine. In each EYT exercise a short sequence of body movements and simultaneous guided imagery is repeated several times. In this study, the simultaneous effects of two different EYT exercises on cardiac autonomic regulation as assessed by spectral analysis of heart rate variability (HRV) were investigated. Twenty healthy subjects (age: 29.1 ± 9.3 years, 13 female) performed two different EYT exercises (EYT-A and EYT-B) for 8 min. Each EYT exercise was compared against two matched control exercises: control exercise 1 (CE1-A and CE1-B) consisted of a repetition of the body movements of the EYT exercise but without guided imagery, control exercise 2 consisted of walking on the spot (CE2-A and CE2-B). Spectral power of HRV during each exercise was quantified on the basis of Holter ECG recordings. During EYT-A the frequency of the peak oscillation in the very low frequency (VLF) band matched the repetition rate of the sequence of body movements (0.02 Hz). Low frequency (LF) oscillations were augmented when compared to the control exercises (EYT-A: 7.31 ± 0.84, CE1-A: 6.98 ± 0.90, CE2-A: 6.52 ± 0.87 ln ms(2), p exercises (EYT-B: 9.32 ± 0.82, CE1-B: 6.31 ± 0.75, CE2-B: 6.04 ± 0.80 ln ms(2), p exercises clearly affected cardiac autonomic regulation in a rhythmic manner according to the stimulus of the specific body movements of each EYT exercise. These results offer a physiological basis to develop a rationale for specific clinical indications of these EYT exercises such as stress reduction or prevention of hypertension. DRKS00006760 (registered on 10/10/2014, i.e. retrospective registration); view details at http://www.drks.de/DRKS00006760.

  19. Current Treatment Strategies for Heart Failure: Role of Device Therapy and LV Reconstruction.

    Science.gov (United States)

    Janaswamy, Praneeth; Walters, Tomos E; Nazer, Babak; Lee, Randall J

    2016-09-01

    Medical care of heart failure (HF) begins with the determination of the cause of the heart failure and diagnosing potential reversible causes (i.e., coronary heart disease, hyperthyroidism, etc.). Medical therapy includes pharmacological and nonpharmacological strategies that limit and/or reverse the signs and symptoms of HF. Initial behavior modification includes dietary sodium and fluid restriction to avoid weight gain; and encouraging physical activity when appropriate. Optimization of medical therapy is the first line of treatment that includes the use of diuretics, vasodilators (i.e., ACE inhibitors or ARBs), beta blockers, and potentially inotropic agents and anticoagulation depending on the patient's severity of heart failure and LV dysfunction. As heart failure advances despite optimized medical management, cardiac resynchronization therapy (CRT), and implantable cardioverter defibrillators (ICDs) are appropriate device therapies. The development of progressive end-stage HF, despite maximal medical therapy, necessitates the consideration of mechanical circulatory devices such as ventricular assist devices (VADs) either as a bridge to heart transplantation or as destination therapy. Despite the advances in the treatment of heart failure, there is still a large morbidity and mortality associated with HF, thus the need to develop newer strategies for the treatment of HF.

  20. Pharmacological Therapy in the Heart as an Alternative to Cellular Therapy: A Place for the Brain Natriuretic Peptide?

    Directory of Open Access Journals (Sweden)

    Nathalie Rosenblatt-Velin

    2016-01-01

    Full Text Available The discovery that stem cells isolated from different organs have the ability to differentiate into mature beating cardiomyocytes has fostered considerable interest in developing cellular regenerative therapies to treat cardiac diseases associated with the loss of viable myocardium. Clinical studies evaluating the potential of stem cells (from heart, blood, bone marrow, skeletal muscle, and fat to regenerate the myocardium and improve its functional status indicated that although the method appeared generally safe, its overall efficacy has remained modest. Several issues raised by these studies were notably related to the nature and number of injected cells, as well as the route and timing of their administration, to cite only a few. Besides the direct administration of cardiac precursor cells, a distinct approach to cardiac regeneration could be based upon the stimulation of the heart’s natural ability to regenerate, using pharmacological approaches. Indeed, differentiation and/or proliferation of cardiac precursor cells is controlled by various endogenous mediators, such as growth factors and cytokines, which could thus be used as pharmacological agents to promote regeneration. To illustrate such approach, we present recent results showing that the exogenous administration of the natriuretic peptide BNP triggers “endogenous” cardiac regeneration, following experimental myocardial infarction.

  1. Comparison of clinical results of pharmaceutical and surgical therapy in patients with severe chronic heart failure

    Directory of Open Access Journals (Sweden)

    Kotsoeva О.Т.

    2016-06-01

    Full Text Available The aim of the presented paper is a meta-analysis of clinical studies on the comparative effectiveness of pharmaceutical therapy and surgical treatment such as cardiac resynchronization therapy (CRT, cardiac resynchronization therapy with cardioversion-defibrillation (CRT-D, circulatory support system and heart transplantation in patients with severe chronic heart failure (CHF. Material and Methods. Results of 41 clinical studies (29799 patients with severe CHF were included in a meta-analysis. Data search was conducted in the following databases: Medline, Medscape, Pubmed, and websites dedicated to clinical research (National Institutes of Health, Clinical Center, ClinicalStudyResults.org, ClinicalTrials.gov. Results. As compared with pharmaceutical therapy, surgical treatment of severe CHF is better to reduce fatal risk, incidence of decompensation of CHF, frequency of cardiac arrhythmias, the need to perform or re-perform heart transplantation. It is also shown that CRT better reduced the mortality from progression of heart failure than heart transplantation. Both pharmaceutical therapy and surgical treatment improved functional class of CHF and quality of patients' life, but does not affect the left ventricular ejection fraction. Conclusion. It was found out that there was a number of significant advantages of surgical treatment of severe CHF, compared with pharmaceutical therapy. However, it is still a number of unresolved issues (particularly in relation to heart transplantation on the effectiveness comparing pharmaceutical and surgical therapies of severe CHF

  2. Exercise training as a therapy for chronic heart failure: can older people benefit?

    Science.gov (United States)

    Witham, Miles D; Struthers, Allan D; McMurdo, Marion E T

    2003-05-01

    Despite recent advances in pharmacological therapy, chronic heart failure remains a major cause of morbidity and mortality in older people. Studies of exercise training in younger, carefully selected patients with heart failure have shown improvements in symptoms and exercise capacity and in many pathophysiological aspects of heart failure, including skeletal myopathy, ergoreceptor function, heart rate variability, endothelial function, and cytokine expression. Data on mortality and hospitalization are lacking, and effects on everyday activity, depression, and quality of life are unclear. Exercise therapy for patients with heart failure appears to be safe and has the potential to improve function and quality of life in older people with heart failure. To realize these potential benefits, exercise programs that are suitable for older, frail people need to be established and tested in an older, frail, unselected population with comorbidities.

  3. Time Course of Cell Sheet Adhesion to Porcine Heart Tissue after Transplantation.

    Science.gov (United States)

    Chang, Dehua; Shimizu, Tatsuya; Haraguchi, Yuji; Gao, Shuai; Sakaguchi, Katsuhisa; Umezu, Mitsuo; Yamato, Masayuki; Liu, Zhongmin; Okano, Teruo

    2015-01-01

    Multilayered cell sheets have been produced from bone marrow-derived mesenchymal stem cells (MSCs) for investigating their adhesion properties onto native porcine heart tissue. Once MSCs reached confluence after a 7-day culture on a temperature-responsive culture dish, a MSCs monolayer spontaneously detached itself from the dish, when the culture temperature was reduced from 37 to 20°C. The basal extracellular matrix (ECM) proteins of the single cell sheet are preserved, because this technique requires no proteolytic enzymes for harvesting cell sheet, which become a basic building block for assembling a multilayer cell sheet. The thickness of multilayered cell sheets made from three MSC sheets was found to be approximately 60 μm. For investigating the adhesion properties of the basal and apical sides, the multilayered cell sheets were transplanted onto the surface of the heart's left ventricle. Multilayered cell sheets were histological investigated at 15, 30, 45 and 60 minutes after transplantation by hematoxylin eosin (HE) and azan dyes to determine required time for the adhesion of the multilayered sheets following cell-sheet transplantation. The results showed that only the basal side of multilayered cell sheets significantly enhanced the sheets adhesion onto the surface of heart 30 minutes after transplantation. This study concluded that (1) cell sheets had to be transplanted with its basal side onto the surface of heart tissue and (2) at least 30 minutes were necessary for obtaining the histological adhesion of the sheets to the heart tissue. This study provided clinical evidence and parameters for the successful application of MSC sheets to the myocardium and allowed cell sheet technology to be adapted clinical cell-therapy for myocardial diseases.

  4. Photodynamic therapy for basal cell carcinoma.

    Science.gov (United States)

    Fargnoli, Maria Concetta; Peris, Ketty

    2015-11-01

    Topical photodynamic therapy is an effective and safe noninvasive treatment for low-risk basal cell carcinoma, with the advantage of an excellent cosmetic outcome. Efficacy of photodynamic therapy in basal cell carcinoma is supported by substantial research and clinical trials. In this article, we review the procedure, indications and clinical evidences for the use of photodynamic therapy in the treatment of basal cell carcinoma.

  5. Transvenous biventricular pacing in a child after congenital heart surgery as an alternative therapy for congestive heart failure

    NARCIS (Netherlands)

    Blom, Nico A.; Bax, Jeroen J.; Ottenkamp, Jaap; Schalij, Martin J.

    2003-01-01

    Transvenous Biventricular Pacing in Children. Cardiac resynchronization therapy improves short-term and long-term hemodynamics in adult patients with congestive heart failure and left bundle branch block. We describe the feasibility of transvenous biventricular pacemaker implantation in a 6-year-old

  6. Cell Therapy for Parkinson’s Disease

    Science.gov (United States)

    Kameda, Masahiro; Sasaki, Tatsuya; Tajiri, Naoki; Date, Isao

    2017-01-01

    Cell therapy for Parkinson’s disease (PD) began in 1979 with the transplantation of fetal rat dopamine-containing neurons that improved motor abnormalities in the PD rat model with good survival of grafts and axonal outgrowth. Thirty years have passed since the 2 clinical trials using cell transplantation for PD patients were first reported. Recently, cell therapy is expected to develop as a realistic treatment option for PD patients owing to the advancement of biotechnology represented by pluripotent stem cells. Medication using levodopa, surgery including deep brain stimulation, and rehabilitation have all been established as current therapeutic strategies. Strong therapeutic effects have been demonstrated by these treatment methods, but they have been unable to stop the progression of the disease. Fortunately, cell therapy might be a key for true neurorestoration. This review article describes the historical development of cell therapy for PD, the current status of cell therapy, and the future direction of this treatment method. PMID:29113472

  7. Advanced Heart Failure Therapies for Cancer Therapeutics-Related Cardiac Dysfunction.

    Science.gov (United States)

    Bianco, Christopher M; Al-Kindi, Sadeer G; Oliveira, Guilherme H

    2017-04-01

    End-stage heart failure in cancer survivors may result from cardiotoxic chemotherapy and/or chest radiation and require advanced therapies, including left ventricular assist devices (LVADs) and transplantation. Traditionally, such therapies have been underutilized in cancer survivors owing to lack of experience and perceived risk of cancer recurrence. Recent data from large registries, however, have shown excellent outcomes of LVADs and transplantation in cancer survivors, albeit subject to careful selection and special considerations. This article summarizes all aspects of advanced heart failure therapies in patients with cancer therapy-related cardiac dysfunction and underscores the need for careful selection of these candidates. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. The association between early menopause and risk of ischaemic heart disease: Influence of Hormone Therapy?

    DEFF Research Database (Denmark)

    Løkkegaard, E; Andersen, Zorana Jovanovic; Heitmann, B L

    2006-01-01

    Randomised clinical trials find no protection against development of ischaemic heart disease by use of Hormone Therapy (HT) after the age of 50 years. Observational studies suggest that early menopause is a risk factor for ischaemic heart disease. Yet, a clinical very relevant question is whether...

  9. ROLE OF THE METABOLITE THERAPY FOR THE TREATMENT OF CHRONIC HEART FAILURE

    Directory of Open Access Journals (Sweden)

    L. N. Maksimova

    2013-01-01

    Full Text Available Questions of metabolite therapy with drugs based on glutamic acid in patients with chronic heart failure are considered. Possible modes of action of these drugs are presented. Results of the proper study of glutamic acid based drug in chronic heart failure are presented as examples.

  10. HEART FAILURE OF INTENSIVE CARE UNIT SPECIALIST: DIAGNOSIS, FOLLOW-UP, AND THERAPY

    OpenAIRE

    Yıldız, Mustafa

    2006-01-01

    Heart failure is one of the diseases that require intensive care unit. The complication, repetition rates and cost ratios are high. Careful follow-up, a good treatment and device therapy such as mechanical ventilation may be require. An intensive care unit specialist must have been experience in the pathophysiology and treatment of heart failure.

  11. Encapsulated glucagon-like peptide-1-producing mesenchymal stem cells have a beneficial effect on failing pig hearts

    DEFF Research Database (Denmark)

    Wright, Elizabeth J; Farrell, Kelly A; Malik, Nadim

    2012-01-01

    Stem cell therapy is an exciting and emerging treatment option to promote post-myocardial infarction (post-MI) healing; however, cell retention and efficacy in the heart remain problematic. Glucagon-like peptide-1 (GLP-1) is an incretin hormone with cardioprotective properties but a short half...

  12. Emerging Stem Cell Therapies: Treatment, Safety, and Biology

    Directory of Open Access Journals (Sweden)

    Joel Sng

    2012-01-01

    Full Text Available Stem cells are the fundamental building blocks of life and contribute to the genesis and development of all higher organisms. The discovery of adult stem cells has led to an ongoing revolution of therapeutic and regenerative medicine and the proposal of novel therapies for previously terminal conditions. Hematopoietic stem cell transplantation was the first example of a successful stem cell therapy and is widely utilized for treating various diseases including adult T-cell leukemia-lymphoma and multiple myeloma. The autologous transplantation of mesenchymal stem cells is increasingly employed to catalyze the repair of mesenchymal tissue and others, including the lung and heart, and utilized in treating various conditions such as stroke, multiple sclerosis, and diabetes. There is also increasing interest in the therapeutic potential of other adult stem cells such as neural, mammary, intestinal, inner ear, and testicular stem cells. The discovery of induced pluripotent stem cells has led to an improved understanding of the underlying epigenetic keys of pluripotency and carcinogenesis. More in-depth studies of these epigenetic differences and the physiological changes that they effect will lead to the design of safer and more targeted therapies.

  13. THE POSSIBILITY OF USAGE OF METABOLIC CORRECTION THERAPY IN PATIENTS WITH ISCHEMIC HEART DISEASE AND HEART FAILURE

    Directory of Open Access Journals (Sweden)

    I. V. Sergienko

    2015-12-01

    Full Text Available Aim. To estimate an effect of metabolic corrector mildronate on cardiac hemodynamics and endothelium function in patients with ischemic heart disease (IHD and heart failure (HFMaterial and methods. 60 patients with IHD and HF of I-III functional class according to NYHA were included into the study. 30 patients of the main group received mildronate at a daily dose of 1000 mg during 3 months additionally to standard therapy. Patients of the control group took standard therapy only. Cardiac function was estimated by 4D Gated Equilibrium Radionuclide Ventriculography. The endothelium function was measured as endothelium dependent vasodilation.Results. During 3 months mildronate therapy resulted in increase of left ventricular (LV ejection fraction, peak filling and peak ejecting rate of LV.Conclusion. Metabolic corrector mildronate has positive effect on cardiac function in patients with IHD and CHF.

  14. Integration of genomics, proteomics, and imaging for cardiac stem cell therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Hyung J. [Stanford University School of Medicine, Department of Medicine, Division of Cardiology, Stanford, CA (United States); Wilson, Kitch O.; Huang, Mei [Stanford University School of Medicine, Molecular Imaging Program at Stanford, Department of Radiology, Stanford, CA (United States); Wu, Joseph C. [Stanford University School of Medicine, Department of Medicine, Division of Cardiology, Stanford, CA (United States); Stanford University School of Medicine, Molecular Imaging Program at Stanford, Department of Radiology, Stanford, CA (United States)

    2007-06-15

    Cardiac stem cell therapy is beginning to mature as a valid treatment for heart disease. As more clinical trials utilizing stem cells emerge, it is imperative to establish the mechanisms by which stem cells confer benefit in cardiac diseases. In this paper, we review three methods - molecular cellular imaging, gene expression profiling, and proteomic analysis - that can be integrated to provide further insights into the role of this emerging therapy. (orig.)

  15. Could Cells from Your Nose Fix Your Heart? Transplantation of Olfactory Stem Cells in a Rat Model of Cardiac Infarction

    Directory of Open Access Journals (Sweden)

    Cameron McDonald

    2010-01-01

    Full Text Available This study examines the hypothesis that multipotent olfactory mucosal stem cells could provide a basis for the development of autologous cell transplant therapy for the treatment of heart attack. In humans, these cells are easily obtained by simple biopsy. Neural stem cells from the olfactory mucosa are multipotent, with the capacity to differentiate into developmental fates other than neurons and glia, with evidence of cardiomyocyte differentiation in vitro and after transplantation into the chick embryo. Olfactory stem cells were grown from rat olfactory mucosa. These cells are propagated as neurosphere cultures, similar to other neural stem cells. Olfactory neurospheres were grown in vitro, dissociated into single cell suspensions, and transplanted into the infarcted hearts of congeneic rats. Transplanted cells were genetically engineered to express green fluorescent protein (GFP in order to allow them to be identified after transplantation. Functional assessment was attempted using echocardiography in three groups of rats: control, unoperated; infarct only; infarcted and transplanted. Transplantation of neurosphere-derived cells from adult rat olfactory mucosa appeared to restore heart rate with other trends towards improvement in other measures of ventricular function indicated. Importantly, donor-derived cells engrafted in the transplanted cardiac ventricle and expressed cardiac contractile proteins.

  16. Rounding up sickle cells with gene therapy.

    Science.gov (United States)

    Byrne, Leah

    2017-03-15

    A report of a patient treated with ex vivo lentiviral gene transfer to hematopoietic stem cells shows the promise of gene therapy for sickle cell anemia. Copyright © 2017, American Association for the Advancement of Science.

  17. FDA Warns About Stem Cell Therapies

    Science.gov (United States)

    ... Home For Consumers Consumer Updates FDA Warns About Stem Cell Therapies Share Tweet Linkedin Pin it More sharing ... see the boxed section below for more advice. Stem Cell Uses and FDA Regulation The FDA has the ...

  18. Targeting cardiac beta-adrenergic signaling via GRK2 inhibition for heart failure therapy

    Directory of Open Access Journals (Sweden)

    Alessandro eCannavo

    2013-09-01

    Full Text Available Cardiac cells, like those of the other tissues, undergo regulation through membrane-bound proteins known as G protein-coupled receptors (GPCRs. β-adrenergic receptors (βARs are key GPCRs expressed on cardiomyocytes and their role is crucial in cardiac physiology since they regulate inotropic and chronotropic responses of the sympathetic nervous system (SNS. In compromised conditions such as heart failure (HF chronic βAR hyperstimulation occurs via SNS activation resulting in receptor dysregulation and down-regulation and consequently there is a marked reduction of myocardial inotropic reserve and continued loss of pump function. Data has accumulated over the last two decades that a primary culprit in initiating and maintain βAR dysfunction in the injured and stressed heart is GPCR kinase 2 (GRK2, which was originally known as βARK1 (for βAR kinase. GRK2 is up-regulated in the failing heart due to chronic SNS activity and targeting this kinase has emerged as a novel therapeutic strategy in HF. Indeed, its inhibition or genetic deletion in several disparate animal models of HF including a pre-clinical pig model has shown that GRK2 targeting improves functional and morphological parameters of the failing heart. Moreover, non-βAR properties of GRK2 appear to also contribute to its pathological effects and thus, its inhibition will likely complement existing therapies such as βAR blockade. This review will explore recent research regarding GRK2 inhibition, in particular it will focus on the GRK2 inhibitor peptide known as βARKct, which represents new hope in the treatment against HF progression. 

  19. Self-assembling peptide hydrogel enables instant epicardial coating of the heart with mesenchymal stromal cells for the treatment of heart failure.

    Science.gov (United States)

    Ichihara, Yuki; Kaneko, Masahiro; Yamahara, Kenichi; Koulouroudias, Marinos; Sato, Nobuhiko; Uppal, Rakesh; Yamazaki, Kenji; Saito, Satoshi; Suzuki, Ken

    2018-02-01

    Transplantation of mesenchymal stromal cells (MSCs) is an emerging therapy for the treatment of heart failure. However, the delivery method of MSC is currently suboptimal. The use of self-assembling peptide hydrogels, including PuraMatrix ® (PM; 3-D Matrix, Ltd), has been reported for clinical hemostasis and in research models. This study demonstrates the feasibility and efficacy of an advanced approach for MSC-therapy, that is coating of the epicardium with the instantly-produced PM hydrogel incorporating MSCs (epicardial PM-MSC therapy). We optimized the conditions/procedure to produce "instant" 2PM-MSC complexes. After spreading on the epicardium by easy pipetting, the PM-MSC complex promptly and stably adhere to the beating heart. Of note, this treatment achieved more extensive improvement of cardiac function, with greater initial retention and survival of donor MSCs, compared to intramyocardial MSC injection in rat heart failure models. This enhanced efficacy was underpinned by amplified myocardial upregulation of a group of tissue repair-related genes, which led to enhanced repair of the damaged myocardium, i.e. augmented microvascular formation and reduced interstitial fibrosis. These data suggest a potential for epicardial PM-MSC therapy to be a widely-adopted treatment of heart failure. This approach may also be useful for treating diseases in other organs than the heart. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. THIAMINE SUPPLEMENT THERAPY IMPROVES EJECTION FRACTION VALUE IN STAGE II HEART FAILURE PATIENTS

    OpenAIRE

    Jikrona, Rafi; Suharjono, Suharjono; Ahmad, Abraham

    2017-01-01

    Thiamine, also called vitamin B1, is a water soluble vitamin that is involved in the formation of ATP in cells. The active metabolite of thiamine is a co-enzyme thiamine pyrophosphate (TPP) that plays an active role in carbohydrate metabolism and the formation of amino acid binding conjugates. Directly, thiamine may increase energy production in heart muscle cells through such mechanism, whereas in conditions of heart failure, a decrease in the contractility of  heart muscle may be found. The...

  1. Complementary alternative medical therapies for heart surgery patients: feasibility, safety, and impact.

    Science.gov (United States)

    Kshettry, Vibhu R; Carole, Linda Flies; Henly, Susan J; Sendelbach, Sue; Kummer, Barbara

    2006-01-01

    Complementary therapies (touch, music) are used as successful adjuncts in treatment of pain in chronic conditions. Little is known about their effectiveness in care of heart surgery patients. Our objective is to evaluate feasibility, safety, and impact of a complementary alternative medical therapies package for heart surgery patients. One hundred four patients undergoing open heart surgery were prospectively randomized to receive either complementary therapy (preoperative guided imagery training with gentle touch or light massage and postoperative music with gentle touch or light massage and guided imagery) or standard care. Heart rate, systolic and diastolic blood pressure, and pain and tension were measured preoperatively and as pre-tests and post-tests during the postoperative period. Complications were abstracted from the hospital record. Virtually all patients in the complementary therapy group (95%) and 86% in standard care completed the study. Heart rate and blood pressure patterns were similar. Decreases in heart rate and systolic blood pressure in the complementary therapies group were judged within the range of normal values. Complication rates were very low and occurred with similar frequency in both groups. Pretreatment and posttreatment pain and tension scores decreased significantly in the complementary alternative medical therapies group on postoperative days 1 (p < 0.01) and 2 (p < 0.038). The complementary medical therapies protocol was implemented with ease in a busy critical care setting and was acceptable to the vast majority of patients studied. Complementary medical therapy was not associated with safety concerns and appeared to reduce pain and tension during early recovery from open heart surgery.

  2. Regenerating Heart Using a Novel Compound and Human Wharton Jelly Mesenchymal Stem Cells.

    Science.gov (United States)

    Rabbani, Shahram; Soleimani, Masoud; Imani, Mohammad; Sahebjam, Mohammad; Ghiaseddin, Ali; Nassiri, Seyed Mahdi; Majd Ardakani, Jalil; Tajik Rostami, Maryam; Jalali, Arash; Mousanassab, Bahmanshir; Kheradmandi, Mahsa; Ahmadi Tafti, Seyed Hossein

    2017-04-01

    Myocardial infarction is a major problem in health system and most conventional therapy is not led to restoration of the health. Stem cell therapy is a method to regenerate the heart but today appropriate cell source and scaffold selection as extracellular matrix to achieve the best effect is disputing. In this study a combination of human Wharton jelly mesenchymal stem cells (HWJMSCs) with a novel compound consisting polyethylene glycol (PEG), hyaluronic acid and chitosan is presented to heart regeneration. After proliferation and expansion of HWJMSCs, these cells were mixed with scaffold and injected into the infarcted rabbit myocardium. After two months cardiac function and infarcted area were evaluated. Immunohistochemistry performed for vessel count and demonstrating of differentiation ability into cardiomyocytes. To confirm this ability PCR was done. Scanning electron microscope was used to evaluate angiogenesis. Improving cardiac function was higher in cell/scaffold group than the others and it was confirmed by SPECT results which showed least defect size in the myocardium. There were a lot of neoangiogenesis in the target group and also cardiomyogenesis observed in cell/scaffold group. PCR results confirmed the presence of differentiated cardiomyocytes and SEM showed well developed vessel in this group. Comparing macroscopic and microscopic results between all groups revealed that HWJMSC in combination with this scaffold led to brilliant results regarding cardiac function, angiogenesis and cardiogenesis. It is recommended using these cells and materials for cardiac tissue engineering and regeneration therapy. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

  3. Cell-Based Therapies for Diabetic Complications

    Directory of Open Access Journals (Sweden)

    Stella Bernardi

    2012-01-01

    Full Text Available In recent years, accumulating experimental evidence supports the notion that diabetic patients may greatly benefit from cell-based therapies, which include the use of adult stem and/or progenitor cells. In particular, mesenchymal stem cells and the circulating pool of endothelial progenitor cells have so far been the most studied populations of cells proposed for the treatment of vascular complications affecting diabetic patients. We review the evidence supporting their use in this setting, the therapeutic benefits that these cells have shown so far as well as the challenges that cell-based therapies in diabetic complications put out.

  4. Nonclinical safety strategies for stem cell therapies

    Energy Technology Data Exchange (ETDEWEB)

    Sharpe, Michaela E., E-mail: michaela_sharpe@yahoo.com [Investigative Toxicology, Drug Safety Research and Development, Pfizer Ltd, Ramsgate Road, Sandwich, CT13 9NJ (United Kingdom); Morton, Daniel [Exploratory Drug Safety, Drug Safety Research and Development, Pfizer Inc, Cambridge, 02140 (United States); Rossi, Annamaria [Investigative Toxicology, Drug Safety Research and Development, Pfizer Ltd, Ramsgate Road, Sandwich, CT13 9NJ (United Kingdom)

    2012-08-01

    Recent breakthroughs in stem cell biology, especially the development of the induced pluripotent stem cell techniques, have generated tremendous enthusiasm and efforts to explore the therapeutic potential of stem cells in regenerative medicine. Stem cell therapies are being considered for the treatment of degenerative diseases, inflammatory conditions, cancer and repair of damaged tissue. The safety of a stem cell therapy depends on many factors including the type of cell therapy, the differentiation status and proliferation capacity of the cells, the route of administration, the intended clinical location, long term survival of the product and/or engraftment, the need for repeated administration, the disease to be treated and the age of the population. Understanding the product profile of the intended therapy is crucial to the development of the nonclinical safety study design.

  5. Regulation of microvascularization in heart failure - an endothelial cell, non-coding RNAs and exosome liaison

    Directory of Open Access Journals (Sweden)

    Rio P. Juni

    2017-03-01

    Full Text Available Heart failure is a complex syndrome involving various pathophysiological processes. An increasing body of evidence shows that the myocardial microvasculature is essential for the homeostasis state and that a decompensated heart is associated with microvascular dysfunction as a result of impaired endothelial angiogenic capacity. The intercellular communication between endothelial cells and cardiomyocytes through various signaling molecules, such as vascular endothelial growth factor, nitric oxide, and non-coding RNAs is an important determinant of cardiac microvascular function. Non-coding RNAs are transported from endothelial cells to cardiomyocytes, and vice versa, regulating microvascular properties and angiogenic processes in the heart. Small-exocytosed vesicles, called exosomes, which are secreted by both cell types, can mediate this intercellular communication. The purpose of this review is to highlight the contribution of the microvasculature to proper heart function maintenance by focusing on the interaction between cardiac endothelial cells and myocytes with a specific emphasis on non-coding RNAs (ncRNAs in this form of cell-to-cell communication. Finally, the potential of ncRNAs as targets for angiogenesis therapy will also be discussed.

  6. Combining angiogenic gene and stem cell therapies for myocardial infarction.

    Science.gov (United States)

    Pons, Jennifer; Huang, Yu; Takagawa, Junya; Arakawa-Hoyt, Janice; Ye, Jianqin; Grossman, William; Kan, Yuet Wai; Su, Hua

    2009-09-01

    Transplantation of stem cells from various sources into infarcted hearts has the potential to promote myocardial regeneration. However, the regenerative capacity is limited partly as a result of the low survival rate of the transplanted cells in the ischemic myocardium. In the present study, we tested the hypothesis that combining cell and angiogenic gene therapies would provide additive therapeutic effects via co-injection of bone marrow-derived mesenchymal stem cells (MSCs) with an adeno-associated viral vector (AAV), MLCVEGF, which expresses vascular endothelial growth factor (VEGF) in a cardiac-specific and hypoxia-inducible manner. MSCs isolated from transgenic mice expressing green fluorescent protein and MLCVEGF packaged in AAV serotype 1 capsid were injected into mouse hearts at the border of ischemic area, immediately after occlusion of the left anterior descending coronary, individually or together. Engrafted cells were detected and quantified by real-time polymerase chain reaction and immunostaining. Angiogenesis and infarct size were analyzed on histological and immunohistochemical stained sections. Cardiac function was analyzed by echocardiography. We found that co-injection of AAV1-MLCVEGF with MSCs reduced cell loss. Although injection of MSCs and AAV1-MLCVEGF individually improved cardiac function and reduced infarct size, co-injection of MSC and AAV1-MLCVEGF resulted in the best improvement in cardiac function as well as the smallest infarct among all groups. Moreover, injection of AAV1-MLCVEGF induced neovasculatures. Nonetheless, injection of MSCs attracted endogenous stem cell homing and increased scar thickness. Co-injection of MLCVEGF and MSCs in ischemic hearts can result in better cardiac function and MSC survival, compared to their individual injections, as a result of the additive effects of each therapy.

  7. PATIENT WITH CHRONIC HEART FAILURE. RATIONAL CHOICE OF THERAPY

    Directory of Open Access Journals (Sweden)

    O. M. Drapkina

    2017-01-01

    Full Text Available The theory of chronic hyperactivation of neurohormonal systems, in particular, sympathoadrenal and renin-angiotensin-aldosterone, is the basis of modern concepts of the pathogenesis of heart failure. The medicinal blocking of these two systems has proved to be effective in the treatment of heart failure with reduced ejection fraction (<40%. Antagonists of mineralocorticoid receptors, along with angiotensin-converting enzyme inhibitors and beta-blockers, are neurohumoral modulators. They are used to treat patients with heart failure with reduced ejection fraction. The prescription of mineralocorticoid receptor antagonists in clinical practice remains insufficient despite their high efficacy. Demonstration of the site of mineralocorticoid receptor antagonists in the complex treatment of a patient with chronic heart failure and diabetes type 2 is the goal of this article.

  8. Separation of Beating Cardiac Myocytes from Suspensions of Heart Cells

    Science.gov (United States)

    Pretlow, Thomas G.; Glick, Melvin R.; Reddy, William J.

    1972-01-01

    Heart cells were obtained in suspension after incubation with collagenase and hyaluronidase in Saline A. Cardiac myocytes were separated by isopycnic centrifugation in 88.6 to 92.4% purity from other heart cells with different densities, and by velocity or rate-zonal sedimentation, in 92.8 to 97.4% purity from heart cells with different diameters. A previously described computer integration of the differential sedimentation equation was used to determine the centrifugal force, duration of centrifugation and gradient design, which would permit the separation of cardiac myocytes from other heart cells by velocity sedimentation. The myocytes continued to contract rhythmically after being recovered from the density gradients. Velocity sedimentation was superior to isopycnic sedimentation for the separation of cardiac myocytes from heart cell suspensions because it gave the most highly purified myocytes, resulted in recovery of the largest proportion of myocytes in purified fractions from the gradient and required lower centrifugal forces for shorter periods of time. The potential significance of the availability of pure cardiac myocytes is discsused. ImagesFig 2Fig 1 PMID:4336547

  9. Current Biosafety Considerations in Stem Cell Therapy

    Science.gov (United States)

    Mousavinejad, Masoumeh; Andrews, Peter W.; Shoraki, Elham Kargar

    2016-01-01

    Stem cells can be valuable model systems for drug discovery and modelling human diseases as well as to investigate cellular interactions and molecular events in the early stages of development. Controlling the differentiation of stem cells into specific germ layers provides a potential source of highly specialized cells for therapeutic applications. In recent years, finding individual properties of stem cells such as their ultimate self-renewal capacity and the generation of particular cell lines by differentiation under specific culture conditions underpins the development of regenerative therapies. These futures make stem cells a leading candidate to treat a wide range of diseases. Nevertheless, as with all novel treatments, safety issues are one of the barriers that should be overcome to guarantee the quality of a patient’s life after stem cell therapy. Many studies have pointed to a large gap in our knowledge about the therapeutic applications of these cells. This gap clearly shows the importance of biosafety concerns for the current status of cell-based therapies, even more than their therapeutic efficacy. Currently, scientists report that tumorigenicity and immunogenicity are the two most important associated cell-based therapy risks. In principle, intrinsic factors such as cell characteristics and extrinsic elements introduced by manufacturing of stem cells can result in tumor formation and immunological reactions after stem cell transplantation. Therapeutic research shows there are many biological questions regarding safety issues of stem cell clinical applications. Stem cell therapy is a rapidly advancing field that needs to focus more on finding a comprehensive technology for assessing risk. A variety of risk factors (from intrinsic to extrinsic) should be considered for safe clinical stem cell therapies. PMID:27540533

  10. Strategies for future histocompatible stem cell therapy

    DEFF Research Database (Denmark)

    Nehlin, Jan; Barington, Torben

    2009-01-01

    Stem cell therapy based on the safe and unlimited self-renewal of human pluripotent stem cells is envisioned for future use in tissue or organ replacement after injury or disease. A gradual decline of regenerative capacity has been documented among the adult stem cell population in some body organs...... a developmental lineage, would facilitate the transplantation of organ/tissue-specific adult stem cells or terminally differentiated somatic cells to improve the function of diseased organs or tissues in an individual. Here, we present an overview of various experimental cell therapy technologies based on the use...... during the aging process. Recent progress in human somatic cell nuclear transfer and inducible pluripotent stem cell technologies has shown that patient-derived nuclei or somatic cells can be reprogrammed in vitro to become pluripotent stem cells, from which the three germ layer lineages can be generated...

  11. Stem cell therapy for amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Zhijuan Mao

    2015-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disorder characterized by the loss of motor neurons. Currently, no effective therapy is available to treat ALS, except for Riluzole, which has only limited clinical benefits. Stem-cell-based therapy has been intensively and extensively studied as a potential novel treatment strategy for ALS and has been shown to be effective, at least to some extent. In this article, we will review the current state of research on the use of stem cell therapy in the treatment of ALS and discuss the most promising stem cells for the treatment of ALS.

  12. Bone marrow cell migration to the heart in a chimeric mouse model of acute chagasic disease

    Science.gov (United States)

    Irion, Camila Iansen; Paredes, Bruno Diaz; Brasil, Guilherme Visconde; da Cunha, Sandro Torrentes; Paula, Luis Felipe; Carvalho, Alysson Roncally; de Carvalho, Antonio Carlos Campos; Carvalho, Adriana Bastos; Goldenberg, Regina Coeli dos Santos

    2017-01-01

    BACKGROUND Chagas disease is a public health problem caused by infection with the protozoan Trypanosoma cruzi. There is currently no effective therapy for Chagas disease. Although there is some evidence for the beneficial effect of bone marrow-derived cells in chagasic disease, the mechanisms underlying their effects in the heart are unknown. Reports have suggested that bone marrow cells are recruited to the chagasic heart; however, studies using chimeric mouse models of chagasic cardiomyopathy are rare. OBJECTIVES The aim of this study was to investigate the migration of bone marrow cells to the heart after T. cruzi infection in a model of chagasic disease in chimeric mice. METHODS To obtain chimerical mice, wild-type (WT) C57BL6 mice were exposed to full body irradiation (7 Gy), causing bone marrow ablation. Then, bone marrow cells from green fluorescent protein (GFP)-transgenic mice were infused into the mice. Graft effectiveness was confirmed by flow cytometry. Experimental mice were divided into four groups: (i) infected chimeric (iChim) mice; (ii) infected WT (iWT) mice, both of which received 3 × 104 trypomastigotes of the Brazil strain; (iii) non-infected chimeric (Chim) mice; and (iv) non-infected WT mice. FINDINGS At one-month post-infection, iChim and iWT mice showed first degree atrioventricular block with decreased heart rate and treadmill exercise parameters compared to those in the non-infected groups. MAIN CONCLUSIONS iChim mice showed an increase in parasitaemia, myocarditis, and the presence of amastigote nests in the heart tissue compared to iWT mice. Flow cytometry analysis did not detect haematopoietic progenitor cells in the hearts of infected mice. Furthermore, GFP+ cardiomyocytes were not detected in the tissues of chimeric mice. PMID:28767980

  13. Increased mortality after dronedarone therapy for severe heart failure

    DEFF Research Database (Denmark)

    Køber, Lars; Torp-Pedersen, Christian; McMurray, John J V

    2008-01-01

    BACKGROUND: Dronedarone is a novel antiarrhythmic drug with electrophysiological properties that are similar to those of amiodarone, but it does not contain iodine and thus does not cause iodine-related adverse reactions. Therefore, it may be of value in the treatment of patients with heart failure....... METHODS: In a multicenter study with a double-blind design, we planned to randomly assign 1000 patients who were hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunction to receive 400 mg of dronedarone twice a day or placebo. The primary end point was the composite...... of death from any cause or hospitalization for heart failure. RESULTS: After inclusion of 627 patients (310 in the dronedarone group and 317 in the placebo group), the trial was prematurely terminated for safety reasons, at the recommendation of the data and safety monitoring board, in accordance...

  14. Intracoronary Injection of CD34-Cells in Chronic Ischemic Heart Failure

    DEFF Research Database (Denmark)

    Hansen, Morten; Nyby, Sebastian; Eifer Møller, Jacob

    2014-01-01

    was significantly associated with survival (hazard ratio: 0.90, 95% CI: 0.82-1.00, p = 0.04). Conclusions: Intracoronary injections of a high number of CD34(+) cells may have a beneficial effect on chronic ischemic heart failure in terms of long-term survival. © 2014 S. Karger AG, Basel.......Objectives: Seven years ago, the DanCell study was carried out to test the hypothesis of improvement in left ventricular ejection fraction (LVEF) following repeated intracoronary injections of autologous bone marrow-derived stem cells (BMSCs) in patients suffering from chronic ischemic heart...... failure. In this post hoc analysis, the long-term effect of therapy is assessed. Methods: 32 patients [mean age 61 (SD ± 9), 81% males] with systolic dysfunction (LVEF 33 ± 9%) received two repeated intracoronary infusions (4 months apart) of autologous BMSCs (1,533 ± 765 × 10(6) BMSCs including 23 ± 11...

  15. Heart failure therapy in diabetic patients-comparison with the recent ESC/EASD guideline

    Directory of Open Access Journals (Sweden)

    Angermann Christiane E

    2011-02-01

    Full Text Available Abstract Background To assess heart failure therapies in diabetic patients with preserved as compared to impaired systolic ventricular function. Methods 3304 patients with heart failure from 9 different studies were included (mean age 63 ± 14 years; out of these, 711 subjects had preserved left ventricular ejection fraction (≥ 50% and 994 patients in the whole cohort suffered from diabetes. Results The majority (>90% of heart failure patients with reduced ejection fraction (SHF and diabetes were treated with an ACE inhibitor (ACEi or angiotensin receptor blocker (ARB or with beta-blockers. By contrast, patients with diabetes and preserved ejection fraction (HFNEF were less likely to receive these substance classes (p Conclusions Diabetic patients with HFNEF received less heart failure medication and showed a poorer control of blood pressure as compared to diabetic patients with SHF. SHF patients with diabetes were less likely to receive aldosterone receptor blocker therapy, irrespective of renal function.

  16. [Magnetic nanoparticles as tools for cell therapy].

    Science.gov (United States)

    Wilhelm, Claire; Gazeau, Florence

    2012-01-01

    Labelling living cells with magnetic nanoparticles creates opportunities for numerous biomedical applications such as Magnetic Resonance Imaging (MRI) cell tracking, cell manipulation, cell patterning for tissue engineering and magnetically-assisted cell delivery. The unique advantage of magnetic-based methods is to activate or monitor cell behavior by a remote stimulus, the magnetic field. Cell labelling methods using superparamagnetic nanoparticles have been widely developed, showing no adverse effect on cell proliferation and functionalities while conferring magnetic properties to various cell types. This paper first describes how cells can become responsive to magnetic field by safely internalizing magnetic nanoparticles. We next show how magnetic cells can be detected by MRI, giving the opportunity for non-invasive in vivo monitoring of cell migration. We exemplify the fact that MRI cell tracking has become a method of choice to follow the fate of administrated cells in cell therapy assay, whether the cells are grafted locally or administrated in the circulation. Finally we give different examples of magnetic manipulation of cells and their applications to regenerative medicine. Magnetic cell manipulation are forecasted to be more and more developed, in order to improve tissue engineering technique and assist cell-based therapies. Owing to the clinical approval of iron-oxide nanoparticles as MRI contrast agent, there is no major obstacle in the translation to human clinics of the magnetic methods summarized in this paper. © Société de Biologie, 2013.

  17. Understanding the application of stem cell therapy in cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Sharma RK

    2012-10-01

    Full Text Available Rakesh K Sharma, Donald J Voelker, Roma Sharma, Hanumanth K ReddyUniversity of Arkansas for Medical Sciences, Medical Center of South Arkansas, El Dorado, AR, USAAbstract: Throughout their lifetime, an individual may sustain many injuries and recover spontaneously over a period of time, without even realizing the injury in the first place. Wound healing occurs due to a proliferation of stem cells capable of restoring the injured tissue. The ability of adult stem cells to repair tissue is dependent upon the intrinsic ability of tissues to proliferate. The amazing capacity of embryonic stem cells to give rise to virtually any type of tissue has intensified the search for similar cell lineage in adults to treat various diseases including cardiovascular diseases. The ability to convert adult stem cells into pluripotent cells that resemble embryonic cells, and to transplant those in the desired organ for regenerative therapy is very attractive, and may offer the possibility of treating harmful disease-causing mutations. The race is on to find the best cells for treatment of cardiovascular disease. There is a need for the ideal stem cell, delivery strategies, myocardial retention, and time of administration in the ideal patient population. There are multiple modes of stem cell delivery to the heart with different cell retention rates that vary depending upon method and site of injection, such as intra coronary, intramyocardial or via coronary sinus. While there are crucial issues such as retention of stem cells, microvascular plugging, biodistribution, homing to myocardium, and various proapoptotic factors in the ischemic myocardium, the regenerative potential of stem cells offers an enormous impact on clinical applications in the management of cardiovascular diseases.Keywords: stem cell therapy, stem cell delivery, cardiovascular diseases, myocardial infarction, cardiomyopathy

  18. Antithrombotic therapy in atrial fibrillation associated with valvular heart disease

    DEFF Research Database (Denmark)

    Lip, Gregory Y H; Collet, Jean Philippe; Caterina, Raffaele de

    2017-01-01

    Atrial fibrillation (AF) is a major worldwide public health problem, and AF in association with valvular heart disease (VHD) is also common. However, management strategies for this group of patients have been less informed by randomized trials, which have largely focused on 'non-valvular AF' pati...

  19. Stem Cell Therapy in Acute Myocardial Infarction: A Pot of Gold or Pandora's Box

    Directory of Open Access Journals (Sweden)

    V. K. Shah

    2011-01-01

    Full Text Available Stem cell therapy for conditions characterized by myocyte loss in myocardial infarction and heart failure is intuitively appealing. Stem cells from various sources, including heart itself in preclinical and animal studies, have shown the potential to improve the function of ventricular muscle after ischaemic injury. The clinical experience from worldwide studies have indicated the safety profile but with modest benefits. The predominant mechanisms of transplanted cells for improving cardiac function have pointed towards paracrine effects rather than transdifferentiation into cardiomyocytes. Thus, further investigations should be encouraged towards bench side and bedside to resolve various issues for ensuring the correct type and dosing of cells, time, and method of delivery and identify correct mechanism of functional improvement. An interdisciplinary effort at the scientific, clinical, and the government front will bring successful realization of this therapy for healing the heart and may convert what seems now a Pandora's Box into a Pot of Gold.

  20. 'Heart-talk:' considering the role of the heart in therapy as evidenced in the Quran and medical research.

    Science.gov (United States)

    Hussain, Feryad

    2013-12-01

    The emphasis on scientific approaches and evidence-based therapy has been a key force in developing and refining existing models of therapy. While this has been unquestioningly invaluable, it has similarly restricted the development and so implementation of those models that do not lend themselves easily to current research methodology, since the lack of evidence-practice research means they are not considered as 'legitimate' therapeutic practice. That the mind and body have an inter-dependent relationship is readily evidenced in numerous religious texts, but the lack of acknowledgement of that relationship in contemporary therapeutic approaches means that patients are not able to benefit from its use in sessions. Ironically, it is current developments in medical research that have discovered the reality around this relationship that have enabled such models to be further explore within an accepted context of evidence-based practice. This paper highlights the relationship between the heart and brain function as evidenced with brief reference to Quranic verses and medical (namely, neurocardiological) research. Further, it raises questions around the implications of this information for therapists working in both physical and mental health. The concept of 'heart talk' is an extension of the term 'heart brain' coined by Dr Armour (Professor of Pharmacology) in 1991 and is suggestive of its use in the world of psychological therapy. It relates to those cognitions which patients suggest come 'from the heart' which though previously dismissed are now suggestive of having some scientific basis and are potentially a legitimate source of information in understanding patients experiences.

  1. Cell therapy for type 1 diabetes

    National Research Council Canada - National Science Library

    Muir, K R; Lima, M J; Docherty, H M; Docherty, K

    2014-01-01

    Cell therapy in the form of human islet transplantation has been a successful form of treatment for patients with type 1 diabetes for over 10 years, but is significantly limited by lack of suitable donor material...

  2. Cell based therapy in Parkinsonism

    NARCIS (Netherlands)

    de Munter, J.P.J.M.; Lee, C.; Wolters, E.C.

    2013-01-01

    Parkinson's disease (PD) is a synucleinopathy-induced chronic progressive neurodegenerative disorder, worldwide affecting about 5 million humans. As of yet, actual therapies are symptomatic, and neuroprotective strategies are an unmet need. Due to their capability to transdifferentiate, to immune

  3. Past and Present of Total Artificial Heart Therapy: A Success Story.

    Science.gov (United States)

    Samak, Mostafa; Fatullayev, Javid; Sabashnikov, Anton; Zeriouh, Mohamed; Rahmanian, Parwis B; Choi, Yeong-Hoon; Wippermann, Jens; Wahlers, Thorsten; Schmack, Bastian; Ruhparwar, Arjang; Dohmen, Pascal M; Karck, Matthias; Popov, Aron-Frederik; Simon, André R; Weymann, Alexander

    2015-09-07

    The totally artificial heart (TAH) is among the most prominent medical innovations of the 21st century, especially due to the increasing population with end-stage heart failure. The progressive course of the disease, its resistance to conventional therapy, and the scarcity of hearts available for transplantation were the prime impetus for developing a TAH, especially when other options of mechanical circulatory assist devices are exhausted. In this review, we narrate the history of TAH, give an overview of its technology, and address the pros and cons of the currently available TAH models in light of published clinical experience.

  4. Ultrafiltration Therapy for Heart Failure: Balancing Likely Benefits against Possible Risks.

    Science.gov (United States)

    Kazory, Amir

    2016-08-08

    Heart failure remains a major public health concern because of its high prevalence, morbidity, mortality, and financial burden. The poor clinical outcomes associated with acute decompensated heart failure, suboptimal efficacy and safety profile of conventional treatment regimens, and unsatisfactory experiences with the newer classes of pharmacologic therapy underlie the interest in the use of extracorporeal isolated ultrafiltration in this setting. In this article, selected mechanistic aspects of ultrafiltration therapy are briefly reviewed followed by a critical overview of the largest trials in this field. I will discuss the clinical relevance of renal dysfunction and decongestion as two commonly used end points of safety and efficacy in the ultrafiltration trials, with emphasis on the emerging pertinent notions that could challenge our conventional thinking. Finally, a number of practical recommendations (e.g., customization of ultrafiltration rates) are provided for ultrafiltration therapy in the setting of acute decompensated heart failure. Because of a paucity of evidence, universally accepted consensus guidelines cannot yet be generated. As such, when considering ultrafiltration therapy for acute decompensated heart failure, the likely benefits should be carefully balanced against the potential risks for an individual patient. A conceivable implication of the ultrafiltration trials is that collaborative heart failure programs benefiting from nephrology expertise and resources could improve the outcomes and reduce the cost. Copyright © 2016 by the American Society of Nephrology.

  5. Stem Cell Therapy for Fanconi Anemia.

    Science.gov (United States)

    Zhang, Qing-Shuo

    2017-07-08

    Stem cell therapy is the administration of stem cells to a patient to treat or prevent a disease. Since stem cells possess the long-term self-renewal capacity and provide daughter cells that differentiate into the specialized cells of each tissue, stem cell therapy will theoretically improve the disease condition for the lifetime of the patient. As the most widely used stem cell therapy, bone marrow transplantation is the treatment of choice for many kinds of blood disorders, including anemias, leukemias, lymphomas, and rare immunodeficiency diseases. For the fatal genetic blood disorder Fanconi anemia, allogeneic bone marrow transplantation has remained the only curative treatment. But the recent advances in stem cell and gene therapy fields may provide promising opportunities for an alternative or even better management of Fanconi anemia. Many of these new ideas and opportunities are also useful for treating other blood diseases that affect hematopoietic stem cells, such as sickle cell anemia, severe combined immunodeficiencies, and beta-thalassemias. In this chapter, these advances along with their challenges and limitations will be thoroughly discussed.

  6. Expanding Applicability of Total Artificial Heart Therapy: The 50-cc SynCardia Total Artificial Heart.

    Science.gov (United States)

    Spiliopoulos, Sotirios; Dimitriou, Alexandros Merkourios; Guersoy, Dilek; Koerfer, Reiner; Tenderich, Gero

    2015-09-01

    The 50-cc SynCardia total artificial heart is designed to facilitate orthotopic replacement of the native ventricles in patients with a body surface area below 1.7 m(2) in need of long-term circulatory support as a result of end-stage biventricular heart failure. We describe the implementation of this technology in a female patient with irreversible cardiogenic shock on the grounds of acute myocardial infarction and chronic ischemic cardiomyopathy. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  7. Blood Transfusion Therapy in Patients with Heart Disease.

    Science.gov (United States)

    1982-04-07

    Harker LA, Malpass TW, Branson HE, Hessel EA II, Slichter SJ. Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: Acquired...decrease in the heart-lung machine. Haemostasis 1973/74;2: 294-303. 202. Malpass TW, Hanson SR, Savage B, Hessel EA II, Harker LA. Prevention of...aureus and Escherichia coli in bank blood. J Lab Clin Med 1972;79:886-92. 223. McClellan MA, Alexander JW. The opsonic activity of stored blood

  8. Alternative Cell Sources to Adult Hepatocytes for Hepatic Cell Therapy.

    Science.gov (United States)

    Pareja, Eugenia; Gómez-Lechón, María José; Tolosa, Laia

    2017-01-01

    Adult hepatocyte transplantation is limited by scarce availability of suitable donor liver tissue for hepatocyte isolation. New cell-based therapies are being developed to supplement whole-organ liver transplantation, to reduce the waiting-list mortality rate, and to obtain more sustained and significant metabolic correction. Fetal livers and unsuitable neonatal livers for organ transplantation have been proposed as potential useful sources of hepatic cells for cell therapy. However, the major challenge is to use alternative cell sources for transplantation that can be derived from reproducible methods. Different types of stem cells with hepatic differentiation potential are eligible for generating large numbers of functional hepatocytes for liver cell therapy to treat degenerative disorders, inborn hepatic metabolic diseases, and organ failure. Clinical trials are designed to fully establish the safety profile of such therapies and to define target patient groups and standardized protocols.

  9. Decongestion: Diuretics and other therapies for hospitalized heart failure.

    Science.gov (United States)

    Vazir, Ali; Cowie, Martin R

    2016-04-01

    Acute heart failure (AHF) is a potentially life-threatening clinical syndrome, usually requiring hospital admission. Often the syndrome is characterized by congestion, and is associated with long hospital admissions and high risk of readmission and further healthcare expenditure. Despite a limited evidence-base, diuretics remain the first-line treatment for congestion. Loop diuretics are typically the first-line diuretic strategy with some evidence that initial treatment with continuous infusion or boluses of high-dose loop diuretic is superior to an initial lower dose strategy. In patients who have impaired responsiveness to diuretics, the addition of an oral thiazide or thiazide-like diuretic to induce sequential nephron blockade can be beneficial. The use of intravenous low-dose dopamine is no longer supported in heart failure patients with preserved systolic blood pressure and its use to assist diuresis in patients with low systolic blood pressures requires further study. Mechanical ultrafiltration has been used to treat patients with heart failure and fluid retention, but the evidence-base is not robust, and its place in clinical practice is yet to be established. Several novel pharmacological agents remain under investigation. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  10. The Woman's Heart: Insights into New Potential Targeted Therapy.

    Science.gov (United States)

    Gianfrilli, Daniele; Pofi, Ricardo; Feola, Tiziana; Lenzi, Andrea; Giannetta, Elisa

    2017-01-01

    Cardiovascular disease is an increasingly common cause of death in women. There is as yet no consensus on the analysis of cardiovascular risk factors with regard to the specific, personalised treatment of pre- and post-menopausal women. Clinically significant cardioprotective and antiremodelling effects have been observed in animal and human studies exploring chronic inhibition of phosphodiesterase type 5 (PDE5). The relationship between the heart, estrogens and PDE5 inhibitors (PDE5is) remains unclear. Experimental data suggest potential beneficial effects on cardiac geometry, function, endothelial function and microvascular coronary flow in women. It was recently postulated that the efficacy of PDE5is is estrogen-dependent in female heart disease. A registered randomised, placebo-controlled study, RECOGITO (NCT01803828), aimed at identifying the genderspecific efficacy of long-term PDE5 inhibition in diabetic cardiomyopathy, is currently recruiting patients. Estrogen receptor modulation could be a new promising approach to heart protection via PDE5is. PDE5is could be indicated as a gender-oriented strategy in modulated cardiac dysfunction and remodelling and in cardiac risk factors for selected cardiovascular diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Stem cells in endodontic therapy

    Directory of Open Access Journals (Sweden)

    Sita Rama Kumar M, Madhu Varma K, Kalyan Satish R, Manikya kumar Nanduri.R, Murali Krishnam Raju S, Mohan rao

    2014-11-01

    Full Text Available Stem cells have the remarkable potential to develop into many different cell types in the body. Serving as a sort of repair system for the body, they can theoretically divide without limit to replenish other cells as long as the person or animal is still alive. However, progress in stem cell biology and tissue engineering may present new options for replacing heavily damaged or lost teeth, or even individual tooth structures. The goal of this review is to discuss the potential impact of dental pulp stem cells on regenerative endodontics.

  12. Cardiomyopathy and cell therapy: ejection fraction improvement and cardiac muscle mass increasing, after a year of bone marrow stem cells transplantation, by magnetic resonance image

    OpenAIRE

    Greco,Oswaldo Tadeu; Zotarelli Filho, Idiberto José; Bellini,Marilanda Ferreira; Bilaqui,Aldemir; Souza Júnior, Artur Soares [UNESP; Ruiz, Milton Artur; Abreu,Ana Carolina de; Jacob,José Luiz Balthazar; Santos, Adriana Barbosa [UNESP

    2013-01-01

    The idiopathic dilated cardiomyopathy (IDC) is one of the major public health problems in the western world. Patients with IDC in functional class IV (New York Health Association - NYHA), even after therapeutic optimization, have high mortality. Stem cell therapy has emerged as a potential therapeutic option for cell death-related heart diseases and several positive effects were assigned to cell therapy in cardiomyopathy. The aim of this study was identify short-term result of cell transplant...

  13. Biomarkers in T cell therapy clinical trials

    Directory of Open Access Journals (Sweden)

    Kalos Michael

    2011-08-01

    Full Text Available Abstract T cell therapy represents an emerging and promising modality for the treatment of both infectious disease and cancer. Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. Biomarkers, operationally defined as biological parameters measured from patients that provide information about treatment impact, play a central role in the development of novel therapeutic agents. In the absence of information about primary clinical endpoints, biomarkers can provide critical insights that allow investigators to guide the clinical development of the candidate product. In the context of cell therapy trials, the definition of biomarkers can be extended to include a description of parameters of the cell product that are important for product bioactivity. This review will focus on biomarker studies as they relate to T cell therapy trials, and more specifically: i. An overview and description of categories and classes of biomarkers that are specifically relevant to T cell therapy trials, and ii. Insights into future directions and challenges for the appropriate development of biomarkers to evaluate both product bioactivity and treatment efficacy of T cell therapy trials.

  14. Cell-based therapy for kidney disease.

    Science.gov (United States)

    Chung, Hyun Chul; Ko, In Kap; Atala, Anthony; Yoo, James J

    2015-06-01

    The prevalence of renal disease continues to increase worldwide. When normal kidney is injured, the damaged renal tissue undergoes pathological and physiological events that lead to acute and chronic kidney diseases, which frequently progress to end stage renal failure. Current treatment of these renal pathologies includes dialysis, which is incapable of restoring full renal function. To address this issue, cell-based therapy has become a potential therapeutic option to treat renal pathologies. Recent development in cell therapy has demonstrated promising therapeutic outcomes, in terms of restoration of renal structure and function impaired by renal disease. This review focuses on the cell therapy approaches for the treatment of kidney diseases, including various cell sources used, as well recent advances made in preclinical and clinical studies.

  15. Heart failure severity, inappropriate ICD therapy, and novel ICD programming: a MADIT-RIT substudy.

    Science.gov (United States)

    Daimee, Usama A; Vermilye, Katherine; Rosero, Spencer; Schuger, Claudio D; Daubert, James P; Zareba, Wojciech; McNitt, Scott; Polonsky, Bronislava; Moss, Arthur J; Kutyifa, Valentina

    2017-12-01

    The effects of heart failure (HF) severity on risk of inappropriate implantable cardioverter-defibrillator (ICD) therapy have not been thoroughly investigated. We aimed to study the association between HF severity and inappropriate ICD therapy in MADIT-RIT. MADIT-RIT randomized 1,500 patients to three ICD programming arms: conventional (Arm A), high-rate cut-off (Arm B: ≥200 beats/min), and delayed therapy (Arm C: 60-second delay for ≥170 beats/min). We evaluated the association between New York Heart Association (NYHA) class III (n = 256) versus class I-II (n = 251) and inappropriate ICD therapy in Arm A patients with ICD-only and cardiac resynchronization therapy with defibrillator (CRT-D). We additionally assessed benefit of novel ICD programming in Arms B and C versus Arm A by NYHA classification. In Arm A, the risk of inappropriate therapy was significantly higher in those with NYHA III versus NYHA I-II for both ICD (hazard ratio [HR] = 2.55, confidence interval [CI]: 1.51-4.30, P programming significantly reduced inappropriate therapy in patients with both NYHA III (Arm B vs Arm A: HR = 0.08, P programming with high-rate cut-off or delayed detection reduces inappropriate ICD therapies in both mild and moderate HF. © 2017 Wiley Periodicals, Inc.

  16. Cardiac Resynchronization Therapy Defibrillator Treatment in a Child with Heart Failure and Ventricular Arrhythmia

    Directory of Open Access Journals (Sweden)

    Hak Ju Kim

    2016-08-01

    Full Text Available Cardiac resynchronization therapy (CRT is a new treatment for refractory heart failure. However, most patients with heart failure treated with CRT are adults, middle-aged or older with idiopathic or ischemic dilated cardiomyopathy. We treated a 12-year-old boy, who was transferred after cardiac arrest, with dilated cardiomyopathy, left bundle-branch block, and ventricular tachycardia. We performed cardiac resynchronization therapy with a defibrillator (CRT-D. After CRT-D, left ventricular ejection fraction improved from 22% to 4 4% a ssessed by e chocardiog ram 1 year p ostoperatively. On e lectrocardiog ram, Q RS d uration was shortened from 206 to 144 ms. The patient’s clinical symptoms also improved. For pediatric patients with refractory heart failure and ventricular arrhythmia, CRT-D could be indicated as an effective therapeutic option.

  17. Impact of Ejection Fraction on the Clinical Response to Cardiac Resynchronization Therapy in Mild Heart Failure

    DEFF Research Database (Denmark)

    Linde, Cecilia; Daubert, Claude; Abraham, William T

    2013-01-01

    Current guidelines recommend cardiac resynchronization therapy (CRT) in mild heart failure (HF) patients with QRS prolongation and ejection fraction (EF) ≤30%. To assess the effect of CRT in less severe systolic dysfunction, outcomes in the REsynchronization reVErses Remodeling in Systolic left v...

  18. Distinct trajectories of disease-specific health status in heart failure patients undergoing cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Mastenbroek, Mirjam H.; Pedersen, Susanne S.; Meine, Mathias

    2016-01-01

    PURPOSE: It is well known that a significant proportion of heart failure patients (10-44 %) do not show improvement in symptoms or functioning from cardiac resynchronization therapy (CRT), yet no study has examined patient-reported health status trajectories after implantation. METHODS: A cohort...

  19. Intracellular renin disrupts chemical communication between heart cells. Pathophysiological implications

    Directory of Open Access Journals (Sweden)

    Walmor eDe Mello

    2015-01-01

    Full Text Available The influence of intracellular renin on the process of chemical communication between cardiac cells was investigated in cell pairs isolated from the left ventricle of adult Wistar Kyoto rats. The enzyme together with Lucifer yellow CH was dialyzed into one cell of the pair using the whole cell clamp technique. The diffusion of the dye in the dialyzed and in non-dialyzed cell was followed by measuring the intensity of fluorescence in both cells as a function of time. The results indicated that; 1 under normal conditions, Lucifer Yellow flows from cell-to-cell through gap junctions; 2 the intracellular dialysis of renin (100nM disrupts chemical communication-an effect enhanced by simultaneous administration of angiotensinogen (100nM; 3 enalaprilat (10-9M administered to the cytosol together with renin reduced drastically the uncoupling action of the enzyme; 4 aliskiren (10-8M inhibited the effect of renin on chemical communication;5 the possible role of intracellular renin independently of angiotensin II (Ang II was evaluated including the increase of the inward calcium current elicited by the enzyme and the possible role of oxidative stress on the disruption of cell communication; 6 the possible harmful versus the beneficial effect of intracellular renin during myocardial infarction was discussed;7 the present results indicate that intracellular renin due to internalization or in situ synthesis, causes a severe impairment of chemical communication in the heart resulting in derangement of metabolic cooperation with serious consequences for heart function.

  20. Established and emerging cardiovascular magnetic resonance techniques for prognostication and guiding therapy in heart failure.

    Science.gov (United States)

    Swoboda, Peter P; Plein, Sven

    2014-01-01

    The syndrome of heart failure is prevalent and a cause of significant morbidity and mortality. Cardiovascular magnetic resonance (CMR) offers a unique method to quantify the extent of left ventricular dysfunction and also characterize the myocardium, particularly according to the presence and distribution of late gadolinium enhancement. The prognostic value of late gadolinium enhancement in various etiologies of heart failure has been demonstrated. Newer techniques that non-invasively assess the extracellular volume may also add to the prognostic value of CMR in heart failure. Management decisions in patients with heart failure can often be complex. CMR can provide useful information when planning cardiac device therapy and the CMR assessment of viability is key when planning revascularization.

  1. CARDIAC RESYNCHRONIZATION THERAPY OF CHRONIC HEART FAILURE AS «BRIDGE» TO CARDIAC TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    D. V. Shumakov

    2009-01-01

    Full Text Available Cardiac transplantation (CTX remains the gold standard for treatment of terminal forms of heart failure. Nevertheless, all over the world shortage of donors and postoperative complications leads to search of alternative therapeutic strategy. Cardiac resynchronization therapy is discussed alternative CTX. Besides, now it is not clear, whether it is possible to prevent CRT CTX in long-term prospect. Thus, we aspired to estimate long-term clinical results in the big group of candidates to CTX which have received CRT-systems in Institute of Transplantation last years. In total 70 patients are operated, from them 5 patients in connection with condition deterioration heart transplantation has been executed. The received experience shows that at patients with left ventricular dissinhroniсity, which are in a waiting list to heart transplantation, application of method CRT may to prevent or delay necessity for heart transplantation, or to become a link as «bridge» to transplantation. 

  2. Complex multidrug therapy in a patient with pulmonary hypertension before and after orthotopic heart transplantation. A case report.

    Science.gov (United States)

    D'Alto, Michele; Alfano, Dionigia; Maiello, Ciro; Sarubbi, Berardo; Santoro, Giuseppe; Argiento, Paola; Galdieri, Nicola; Russo, Maria G; Cotrufo, Maurizio; Calabrò, Raffaele

    2007-11-01

    Pulmonary arterial hypertension represents an absolute contraindication for heart transplantation. We report the case of a 30-year-old man with end-stage heart failure due to restrictive cardiomyopathy and pulmonary arterial hypertension. A complex multidrug therapy improved pulmonary haemodynamics to the point that orthotopic heart transplantation could be carried out. At 18-month follow-up after heart transplantation, the patient's cardiac function made a full recovery. Larger prospective studies are warranted to support these results.

  3. Corticosteroids, heart failure, and hypertension: a role for immune cells?

    Science.gov (United States)

    Shen, Jimmy Z; Young, Morag J

    2012-12-01

    Aldosterone and its receptor the mineralocorticoid receptor (MR) are best known for their regulation of fluid and electrolyte homeostasis in epithelial cells. However, it is now clear that MR are also expressed in a broad range of nonepithelial tissues including the cardiovascular system. In the heart and vascular tissues, pathological activation of MR promotes cardiovascular inflammation and remodeling for which there is increasing evidence that macrophages and other immune cells (e.g. T cells and dendritic cells) play a significant role. While the glucocorticoids and their receptors have well-described antiinflammatory actions in immune cells, a role for aldosterone and/or the MR in these cells is largely undefined. Emerging evidence, however, suggests that MR signaling may directly or indirectly promote proinflammatory responses in these immune cells. This review will discuss the current understanding of the role of corticosteroid receptors in macrophages and their effect on cardiovascular diseases involving inflammation.

  4. Microencapsulation of Stem Cells for Therapy.

    Science.gov (United States)

    Leslie, Shirae K; Kinney, Ramsey C; Schwartz, Zvi; Boyan, Barbara D

    2017-01-01

    An increasing demand to regenerate tissues from patient-derived sources has led to the development of cell-based therapies using autologous stem cells, thereby decreasing immune rejection of scaffolds coupled with allogeneic stem cells or allografts. Adult stem cells are multipotent and are readily available in tissues such as fat and bone marrow. They possess the ability to repair and regenerate tissue through the production of therapeutic factors, particularly vasculogenic proteins. A major challenge in cell-based therapies is localizing the delivered stem cells to the target site. Microencapsulation of cells provides a porous polymeric matrix that can provide a protected environment, localize the cells to one area, and maintain their viability by enabling the exchange of nutrients and waste products between the encapsulated cells and the surrounding tissue. In this chapter, we describe a method to produce injectable microbeads containing a tunable number of stem cells using the biopolymer alginate. The microencapsulation process involves extrusion of the alginate suspension containing cells from a microencapsulator, a syringe pump to control its flow rate, an electrostatic potential to overcome capillary forces and a reduced Ca(++) cross-linking solution containing a nutrient osmolyte, to form microbeads. This method allows the encapsulated cells to remain viable up to three weeks in culture and up to three months in vivo and secrete growth factors capable of supporting tissue regeneration.

  5. NEW ADVANCES IN BETA-BLOCKER THERAPY IN HEART FAILURE

    Directory of Open Access Journals (Sweden)

    Vincenzo eBarrese

    2013-11-01

    Full Text Available The use of -blockers (BB in heart failure (HF has been considered a contradiction for many years. Considering HF simply as a state of inadequate systolic function, BB were contraindicated because of their negative effects on myocardial contractility. Nevertheless, evidence collected in the past years have suggested that additional mechanisms, such as compensatory neuro-humoral hyperactivation or inflammation, could participate in the pathogenesis of this complex disease. Indeed, chronic activation of the sympathetic nervous system, although initially compensating the reduced cardiac output from the failing heart, increases myocardial oxygen demand, ischemia and oxidative stress; moreover, high catecholamine levels induce peripheral vasoconstriction and increase both cardiac pre- and after-load, thus determining additional stress to the cardiac muscle (1. As a consequence of such a different view of the pathogenic mechanisms of HF, the efficacy of BB in the treatment of HF has been investigated in numerous clinical trials. Results from these trials highlighted BB as valid therapeutic tools in HF, providing rational basis for their inclusion in many HF treatment guidelines. However, controversy still exists about their use, in particular with regards to the selection of specific molecules, since BB differ in terms of adrenergic -receptors selectivity, adjunctive effects on -receptors, and effects on reactive oxygen species and inflammatory cytokines production. Further concerns about the heterogeneity in the response to , as well as the use in specific patients, are matter of debate among clinicians. In this review, we will recapitulate the pharmacological properties and the classification of BB, and the alteration of the adrenergic system occurring during HF that provide a rationale for their use; we will also focus on the possible molecular mechanisms, such as genetic polymorphisms, underlying the different efficacy of molecules

  6. Poststroke Cell Therapy of the Aged Brain

    Directory of Open Access Journals (Sweden)

    Aurel Popa-Wagner

    2015-01-01

    Full Text Available During aging, many neurodegenerative disorders are associated with reduced neurogenesis and a decline in the proliferation of stem/progenitor cells. The development of the stem cell (SC, the regenerative therapy field, gained tremendous expectations in the diseases that suffer from the lack of treatment options. Stem cell based therapy is a promising approach to promote neuroregeneration after brain injury and can be potentiated when combined with supportive pharmacological drug treatment, especially in the aged. However, the mechanism of action for a particular grafted cell type, the optimal delivery route, doses, or time window of administration after lesion is still under debate. Today, it is proved that these protections are most likely due to modulatory mechanisms rather than the expected cell replacement. Our group proved that important differences appear in the aged brain compared with young one, that is, the accelerated progression of ischemic area, or the delayed initiation of neurological recovery. In this light, these age-related aspects should be carefully evaluated in the clinical translation of neurorestorative therapies. This review is focused on the current perspectives and suitable sources of stem cells (SCs, mechanisms of action, and the most efficient delivery routes in neurorestoration therapies in the poststroke aged environment.

  7. Tbx1 coordinates addition of posterior second heart field progenitor cells to the arterial and venous poles of the heart.

    Science.gov (United States)

    Rana, M Sameer; Théveniau-Ruissy, Magali; De Bono, Christopher; Mesbah, Karim; Francou, Alexandre; Rammah, Mayyasa; Domínguez, Jorge N; Roux, Marine; Laforest, Brigitte; Anderson, Robert H; Mohun, Timothy; Zaffran, Stephane; Christoffels, Vincent M; Kelly, Robert G

    2014-10-10

    Cardiac progenitor cells from the second heart field (SHF) contribute to rapid growth of the embryonic heart, giving rise to right ventricular and outflow tract (OFT) myocardium at the arterial pole of the heart, and atrial myocardium at the venous pole. Recent clonal analysis and cell-tracing experiments indicate that a common progenitor pool in the posterior region of the SHF gives rise to both OFT and atrial myocytes. The mechanisms regulating deployment of this progenitor pool remain unknown. To evaluate the role of TBX1, the major gene implicated in congenital heart defects in 22q11.2 deletion syndrome patients, in posterior SHF development. Using transcriptome analysis, genetic tracing, and fluorescent dye-labeling experiments, we show that Tbx1-dependent OFT myocardium originates in Hox-expressing cells in the posterior SHF. In Tbx1 null embryos, OFT progenitor cells fail to segregate from this progenitor cell pool, leading to failure to expand the dorsal pericardial wall and altered positioning of the cardiac poles. Unexpectedly, addition of SHF cells to the venous pole of the heart is also impaired, resulting in abnormal development of the dorsal mesenchymal protrusion, and partially penetrant atrioventricular septal defects, including ostium primum defects. Tbx1 is required for inflow as well as OFT morphogenesis by regulating the segregation and deployment of progenitor cells in the posterior SHF. Our results provide new insights into the pathogenesis of congenital heart defects and 22q11.2 deletion syndrome phenotypes. © 2014 American Heart Association, Inc.

  8. [Organ-protection therapy. A new therapeutic approach for acute heart failure?].

    Science.gov (United States)

    Chivite, David; Formiga, Francesc; Corbella, Xavier

    2014-03-01

    Unlike the prolonged benefit produced by the treatment of chronic heart failure, newer drugs tested for the treatment of acute heart failure in the last decade have failed to provide evidence of clinical benefit beyond some improvement in symptom relief. In particular, no drug has shown the ability to reduce the higher medium- and long-term risk of morbidity and mortality in these patients after an episode of decompensation. Current understanding of the pathophysiology of acute heart failure and its consequences has led to the hypothesis that, beyond symptom control, effective therapies for this syndrome should target not only the hemodynamic changes of the initial phase of the syndrome but should also "protect" the organism from the activation of neurohumoral and inflammatory pathways triggered by the decompensation episode, which persist in time and confer a risk of deleterious effects in several organs and tissues. Serelaxin, a new drug related to the peptidic endogenous hormones of the relaxin family, has recently been shown to provide multiple beneficial effects in terms of "organ protection" - not only in the cardiovascular and renal systems - from these acute heart failure-related deleterious changes. This drug has already been tested in acute heart failure patients with encouraging results in terms of medium-term clinical benefit, rendering serelaxin as a serious candidate for first-line, prognosis-modifying therapy in this syndrome. Copyright © 2014 Elsevier España, S.L. All rights reserved.

  9. Antithrombotic therapy for the CardioWest temporary total artificial heart.

    Science.gov (United States)

    Ensor, Christopher R; Cahoon, William D; Crouch, Michael A; Katlaps, Gundars J; Hess, Michael L; Cooke, Richard H; Gunnerson, Kyle J; Kasirajan, Vigneshwar

    2010-01-01

    The CardioWest temporary total artificial heart serves as a viable bridge to orthotopic heart transplantation in patients who are experiencing end-stage refractory biventricular heart failure. This device is associated with a low, albeit still substantial, risk of thrombosis. Platelet interactions with artificial surfaces are complex and result in continuous activation of contact proteins despite therapeutic anticoagulation. We searched the medical literature (publication dates, January 1962-October 2009) in order to evaluate means of mitigating adverse events that have occurred after implantation of the CardioWest temporary total artificial heart.We conclude that the use of a multitargeted antithrombotic approach, involving anticoagulation (bivalirudin and warfarin) and antiplatelet therapy (dipyridamole and aspirin), can mitigate the procoagulative effects of mechanical circulatory assist devices, particularly those that are associated with the CardioWest temporary total artificial heart. Careful monitoring with use of a variant multisystem approach, involving efficacy tests (thrombelastography and light transmittance aggregometry), safety tests (laboratory analyses), and warfarin genomics, may maximize the therapeutic actions and minimize the bleeding risks that are associated with the multitargeted antithrombotic approach. The development and monitoring of individualized antithrombotic regimens require that informed health professionals appreciate the complexities and grasp the hazards that are associated with these therapies.

  10. Stem Cell Therapy Advances in China.

    Science.gov (United States)

    Hu, Lei; Zhao, Bin; Wang, Songlin

    2017-12-28

    Stem cell therapy is a promising method for the treatment of patients with a wide range of diseases and injuries. With increasing government funds for scientific research in China, stem cell research in China has developed rapidly. The number and quality of publications have increased substantially in the past 5 years. Extensive, high-quality studies have been performed in China in the areas of cell reprograming, stem cell homeostasis, gene modifications, and immunomodulation. Translation studies, including basic and preclinical investigations, have also increased. About 100 stem cell banks have been established in China and 10 stem cell drugs are currently in the approval process. More than 400 stem cell-based clinical trials have been registered in China. With continued state funding, advanced biotechnical support, and the development of regulatory standards for the clinical application of stem cells, further innovations are expected, leading to a boom in stem cell therapy. This review highlights recent achievements of stem cell research in China and discusses future prospects.

  11. Derivation and cardiomyocyte differentiation of induced pluripotent stem cells from heart failure patients.

    Science.gov (United States)

    Zwi-Dantsis, Limor; Huber, Irit; Habib, Manhal; Winterstern, Aaron; Gepstein, Amira; Arbel, Gil; Gepstein, Lior

    2013-06-01

    Myocardial cell replacement therapies are hampered by a paucity of sources for human cardiomyocytes and by the expected immune rejection of allogeneic cell grafts. The ability to derive patient-specific human-induced pluripotent stem cells (hiPSCs) may provide a solution to these challenges. We aimed to derive hiPSCs from heart failure (HF) patients, to induce their cardiomyocyte differentiation, to characterize the generated hiPSC-derived cardiomyocytes (hiPSC-CMs), and to evaluate their ability to integrate with pre-existing cardiac tissue. Dermal fibroblasts from two HF patients were reprogrammed by retroviral delivery of Oct4, Sox2, and Klf4 or by using an excisable polycistronic lentiviral vector. The resulting HF-hiPSCs displayed adequate reprogramming properties and could be induced to differentiate into cardiomyocytes with the same efficiency as control hiPSCs (derived from human foreskin fibroblasts). Gene expression and immunostaining studies confirmed the cardiomyocyte phenotype of the differentiating HF-hiPSC-CMs. Multi-electrode array recordings revealed the development of a functional cardiac syncytium and adequate chronotropic responses to adrenergic and cholinergic stimulation. Next, functional integration and synchronized electrical activities were demonstrated between hiPSC-CMs and neonatal rat cardiomyocytes in co-culture studies. Finally, in vivo transplantation studies in the rat heart revealed the ability of the HF-hiPSC-CMs to engraft, survive, and structurally integrate with host cardiomyocytes. Human-induced pluripotent stem cells can be established from patients with advanced heart failure and coaxed to differentiate into cardiomyocytes, which can integrate with host cardiac tissue. This novel source for patient-specific heart cells may bring a unique value to the emerging field of cardiac regenerative medicine.

  12. Can yoga therapy stimulate stem cell trafficking from bone marrow?

    Directory of Open Access Journals (Sweden)

    Nitya Shree

    2016-07-01

    Full Text Available It has been established that mesenchymal stromal cells (MSCs from bone marrow enter the peripheral circulation intermittently for possible tissue regeneration, repair and to take care of daily wear and tear. This is evident from the detection of MSCs from peripheral blood. The factors governing this migration remain elusive. These MSCs carry out the work of policing and are supposed to repair the injured tissues. Thus, these cells help in maintaining the tissue and organ homeostasis. Yoga and pranayama originated in India and is now being practiced all over the world for positive health. So far, the chemical stimulation of bone marrow has been widely used employing injection of colony stimulating factor. However, the role of physical factors such as mechanical stimulation and stretching has not been substantiated. It is claimed that practicing yoga delays senescence, improves the physiological functions of heart and lung and yoga postures make the body elastic. It remains to be seen whether the yoga therapy promotes trafficking of the stem cells from bone marrow for possible repair and regeneration of worn out and degenerating tissues. We cover in this short review, mainly the role of physical factors especially the yoga therapy on stem cells trafficking from bone marrow.

  13. Can yoga therapy stimulate stem cell trafficking from bone marrow?

    Science.gov (United States)

    Shree, Nitya; Bhonde, Ramesh R

    It has been established that mesenchymal stromal cells (MSCs) from bone marrow enter the peripheral circulation intermittently for possible tissue regeneration, repair and to take care of daily wear and tear. This is evident from the detection of MSCs from peripheral blood. The factors governing this migration remain elusive. These MSCs carry out the work of policing and are supposed to repair the injured tissues. Thus, these cells help in maintaining the tissue and organ homeostasis. Yoga and pranayama originated in India and is now being practiced all over the world for positive health. So far, the chemical stimulation of bone marrow has been widely used employing injection of colony stimulating factor. However, the role of physical factors such as mechanical stimulation and stretching has not been substantiated. It is claimed that practicing yoga delays senescence, improves the physiological functions of heart and lung and yoga postures make the body elastic. It remains to be seen whether the yoga therapy promotes trafficking of the stem cells from bone marrow for possible repair and regeneration of worn out and degenerating tissues. We cover in this short review, mainly the role of physical factors especially the yoga therapy on stem cells trafficking from bone marrow. Copyright © 2016 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

  14. A case of periostitis secondary to voriconazole therapy in a heart transplant recipient.

    Science.gov (United States)

    Wise, Steven M; Wilson, Michael A

    2011-03-01

    A 66-year-old man with a history of heart transplant for idiopathic dilated cardiomyopathy presented with progressive bone pain and myalgias. He has been on voriconazole for a pulmonary Aspergillus infection for 9 months. He had an elevated alkaline phosphatase of 280. There is no history of rheumatologic disease. Drug-induced periostitis has recently been reported in patients on long-term voriconazole therapy after lung transplantation for prophylaxis and treatment of Aspergillus infection. This case demonstrates the same phenomenon in a heart transplant patient. This patient's symptoms improved after discontinuation of voriconazole.

  15. Analysis of malignancies in patients after heart transplantation with subsequent immunosuppressive therapy

    Directory of Open Access Journals (Sweden)

    Rivinius R

    2014-12-01

    Full Text Available Rasmus Rivinius,1 Matthias Helmschrott,1 Arjang Ruhparwar,2 Bastian Schmack,2 Berthold Klein,2 Christian Erbel,1 Christian A Gleissner,1 Mohammadreza Akhavanpoor,1 Lutz Frankenstein,1 Fabrice F Darche,1 Dierk Thomas,1 Philipp Ehlermann,1 Tom Bruckner,3 Hugo A Katus,1 Andreas O Doesch11Department of Cardiology, Angiology and Pneumology, 2Department of Cardiac Surgery, 3Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, GermanyObjective: The aim of this study was to analyze the distribution of malignancies in patients after heart transplantation (HTX and to evaluate the risk factors including immunosuppressive therapy with regard to the development of malignancies and survival. Special emphasis was placed on the effects of a mammalian target of rapamycin (mTOR containing immunosuppressive regimen.Methods: A total of 381 patients (age ≥18 years receiving HTX were included in the present analysis. All patients were followed-up at the University of Heidelberg Heart Center, Heidelberg, Germany. Data were retrieved from the Heidelberg Registry for Heart Transplantation being collected between 1989 and 2014. According to center standard, all patients received induction therapy with anti-thymocyte globulin guided by T-cell monitoring since 1994. The initial immunosuppressive regimen consisting of cyclosporine A (CsA and azathioprine (AZA was replaced by CsA and mycophenolate mofetil (MMF in 2001 and by tacrolimus (TAC and MMF in 2006. Additionally, mTOR inhibitors (everolimus/sirolimus were applied since 2003.Results: Mean recipient age at HTX was 51.2±10.5 years and the mean follow-up period after HTX was 9.7±5.9 years. During follow-up, 130 patients developed a neoplasm (34.1% of total. Subgroup analysis revealed 58 patients with cutaneous malignancy only (15.2%, 56 patients with noncutaneous malignancy only (14.7%, and 16 patients with both cutaneous and noncutaneous malignancy (4.2%. Statistically significant

  16. Biomaterial strategies to improve the efficacy of bone marrow cell therapy for myocardial infarction.

    Science.gov (United States)

    Nadlacki, Bora; Suuronen, Erik J

    2016-12-01

    The feasibility and safety of bone marrow cell (BMC) therapy for cardiac repair following myocardial infarction has been demonstrated in clinical studies, albeit with relatively modest structural and functional benefits. In response to the shortcomings of BMC therapy, the use of biomaterials to enhance cell transplantation is being investigated. Areas covered: The authors first review what has been learned from BMC therapies for the treatment of myocardial infarction in animal models and in clinical trials. Some issues that may be limiting the efficacy of BMC therapy are then described. Lastly, they summarize several biomaterial approaches that have been reported to improve transplanted cell retention and functional outcome, and then focus on how a material can enhance cell function such as proliferation, viability, endothelial differentiation and angiogenic potential. Expert opinion: Improvements are needed if BMC therapy is to become a viable treatment in the clinic. There is optimism that a biomaterial strategy will lead to superior results compared to the cell therapy alone. Through the identification of underlying cell-biomaterial mechanisms, the establishment of comparative standards, and an awareness of the lessons learned from cell therapy trials, biomaterial-enhanced BMC therapy may become an option for the treatment of heart disease patients.

  17. Metabolic and toxicological considerations for diuretic therapy in patients with acute heart failure.

    Science.gov (United States)

    Aspromonte, Nadia; Cruz, Dinna N; Valle, Roberto; Bonello, Monica; Tubaro, Marco; Gambaro, Giovanni; Marchese, Giuseppe; Santini, Massimo; Ronco, Claudio

    2011-09-01

    Diuretics are widely recommended in patients with acute heart failure (AHF). However, loop diuretics predispose patients to electrolyte imbalance and hypovolemia, which in turn leads to neurohormonal activation and worsening renal function (WRF). Unfortunately, despite their widespread use, limited data from randomized clinical trials are available to guide clinicians with the appropriate management of this diuretic therapy. This review focuses on the current management of diuretic therapy and discusses data supporting the efficacy and safety of loop diuretics in patients with AHF. The authors consider the challenges in performing clinical trials of diuretics in AHF, and describe ongoing clinical trials designed to rigorously evaluate optimal diuretic use in this syndrome. The authors review the current evidence for diuretics and suggest hypothetical bases for their efficacy relying on the complex relationship among diuretics, neurohormonal activation, renal function, fluid and sodium management, and heart failure syndrome. Data from several large registries that evaluated diuretic therapy in hospitalized patients with AHF suggest that its efficacy is far from being universal. Further studies are warranted to determine whether high-dose diuretics are responsible for WRF and a higher rate of coexisting renal disease are instead markers of more severe heart failure. The authors believe that monitoring congestion during diuretic therapy in AHF would refine the current approach to AHF treatment. This would allow clinicians to identify high-risk patients and possibly reduce the incidence of complications secondary to fluid management strategies.

  18. Antithrombotic therapy for stroke prevention in atrial fibrillation and mechanical heart valves.

    Science.gov (United States)

    Eikelboom, John W; Hart, Robert G

    2012-05-01

    Cardioembolic strokes account for one-sixth of all strokes and are an important potentially preventable cause of morbidity and mortality. Vitamin K antagonists (e.g., warfarin) are effective for the prevention of cardioembolic stroke in patients with atrial fibrillation (AF) and in those with mechanical heart valves but because of their inherent limitations are underutilized and often suboptimally managed. Antiplatelet therapies have been the only alternatives to warfarin for stroke prevention in AF but although they are safer and more convenient they are much less efficacious. The advent of new oral anticoagulant drugs offers the potential to reduce the burden of cardioembolic stroke by providing access to effective, safe, and more convenient therapies. New oral anticoagulants have begun to replace warfarin for stroke prevention in some patients with AF, based on the favorable results of recently completed phase III randomized controlled trials, and provide for the first time an alternative to antiplatelet therapy for patients deemed unsuitable for warfarin. The promise of the new oral anticoagulants in patients with mechanical heart valves is currently being tested in a phase II trial. If efficacy and safety are demonstrated, the new oral anticoagulants will provide an alternative to warfarin for patients with mechanical heart valves and may also lead to increased use of mechanical valves for patients who would not have received them in the past because of the requirement for long term warfarin therapy. Copyright © 2012 Wiley Periodicals, Inc.

  19. Large animal models for stem cell therapy

    OpenAIRE

    Harding, John; Roberts, R Michael; Mirochnitchenko, Oleg

    2013-01-01

    The field of regenerative medicine is approaching translation to clinical practice, and significant safety concerns and knowledge gaps have become clear as clinical practitioners are considering the potential risks and benefits of cell-based therapy. It is necessary to understand the full spectrum of stem cell actions and preclinical evidence for safety and therapeutic efficacy. The role of animal models for gaining this information has increased substantially. There is an urgent need for nov...

  20. Experimental myocardial stem cell therapy for ST-elevation myocardial infarction

    DEFF Research Database (Denmark)

    Kastrup, Jens; Mygind, Naja D; Qayyum, Abbas A

    2016-01-01

    Ischemic heart disease (IHD) is one of the leading causes of death worldwide and is characterized by the formation of atherosclerotic plaques in the coronary arteries reducing the blood supply to the heart muscle causing ischemia. IHD can result in ST-elevation myocardial infarction (STEMI...... interest in the last 10-15 years especially after STEMI. Many preclinical and clinical studies have shown encouraging results but also very diverse clinical outcomes after stem cell treatment. This diversity in results may be explained by different factors, such as cell isolation technique, infarct......), chronic IHD and heart failure. The patients suffer from chest pain (angina), dyspnea and a reduced quality of life. Common for all these conditions is loss of functional cardiomyocytes and endothelial cells. Stem cell therapy to regenerate injured myocardium is a new treatment option which has gained much...

  1. Experimental myocardial stem cell therapy for ST-elevation myocardial infarction

    DEFF Research Database (Denmark)

    Kastrup, Jens; Mygind, Naja D.; Qayyum, Abbas A.

    2016-01-01

    Ischemic heart disease (IHD) is one of the leading causes of death worldwide and is characterized by the formation of atherosclerotic plaques in the coronary arteries reducing the blood supply to the heart muscle causing ischemia. IHD can result in ST-elevation myocardial infarction (STEMI......), chronic IHD and heart failure. The patients suffer from chest pain (angina), dyspnea and a reduced quality of life. Common for all these conditions is loss of functional cardiomyocytes and endothelial cells. Stem cell therapy to regenerate injured myocardium is a new treatment option which has gained much...... interest in the last 10-15 years especially after STEMI. Many preclinical and clinical studies have shown encouraging results but also very diverse clinical outcomes after stem cell treatment. This diversity in results may be explained by different factors, such as cell isolation technique, infarct...

  2. Stem cell-based therapy : Improving myocardial cell delivery

    NARCIS (Netherlands)

    Feyen, Dries A M|info:eu-repo/dai/nl/413647838; Gaetani, RG; Doevendans, Pieter A.|info:eu-repo/dai/nl/164248366; Sluijter, Joost P G|info:eu-repo/dai/nl/273307908

    2016-01-01

    Stem cell-based therapies form an exciting new class of medicine that attempt to provide the body with the building blocks required for the reconstruction of damaged organs. However, delivering cells to the correct location, while preserving their integrity and functional properties, is a complex

  3. Stem Cell Therapy in Pediatric Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Farnaz Torabian

    2015-06-01

    Full Text Available Pediatric neurological disorders including muscular dystrophy, cerebral palsy, and spinal cord injury are defined as a heterogenous group of diseases, of which some are known to be genetic. The two significant features represented for stem cells, leading to distinguish them from other cell types are addressed as below: they can renew themselves besides the ability to differentiate into cells with special function as their potency. Researches about the role of stem cells in repair of damaged tissues in different organs like myocardium, lung, wound healing, and others are developing. In addition, the use of stem cells in the treatment and improving symptoms of neurological diseases such as autism are known. Many epigenetic and immunological studies on effects of stem cells have been performed. The action of stem cells in tissue repair is a need for further studies. The role of these cells in the secretion of hormones and growth factors in the niche, induction of cell division and differentiation in local cells and differentiation of stem cells in damaged tissue is the samples of effects of tissue repair by stem cells.Cognitive disorders, epilepsy, speech and language disorders, primary sensory dysfunction, and behavioral challenges are symptoms of non-neuromotor dysfunction in half of pediatrics with CP. Occupational therapy, oral medications, and orthopedic surgery for supportive and rehabilitative approaches are part of Conventional remedy for cerebral palsy. This paper summarizes the clinical world wide experience about stem cell based therapeutic procedures for pediatric neurological disorders.

  4. Stem cell therapy in pediatric neurological disorders

    Directory of Open Access Journals (Sweden)

    Farnaz Torabian

    2015-06-01

    Full Text Available Pediatric neurological disorders including muscular dystrophy, cerebral palsy, and spinal cord injury are defined as a heterogenous group of diseases, of which some are known to be genetic. The two significant features represented for stem cells, leading to distinguish them from other cell types are addressed as below: they can renew themselves besides the ability to differentiate into cells with special function as their potency. Researches about the role of stem cells in repair of damaged tissues in different organs like myocardium, lung, wound healing, and others are developing. In addition, the use of stem cells in the treatment and improving symptoms of neurological diseases such as autism are known. Many epigenetic and immunological studies on effects of stem cells have been performed. The action of stem cells in tissue repair is a need for further studies. The role of these cells in the secretion of hormones and growth factors in the niche, induction of cell division and differentiation in local cells and differentiation of stem cells in damaged tissue is the samples of effects of tissue repair by stem cells.Cognitive disorders, epilepsy, speech and language disorders, primary sensory dysfunction, and behavioral challenges are symptoms of non-neuromotor dysfunction in half of pediatrics with CP. Occupational therapy, oral medications, and orthopedic surgery for supportive and rehabilitative approaches are part of Conventional remedy for cerebral palsy. This paper summarizes the clinical world wide experience about stem cell based therapeutic procedures for pediatric neurological disorders.

  5. Remote transplantation of mesenchymal stem cells protects the heart against ischemia-reperfusion injury.

    Science.gov (United States)

    Preda, Mihai Bogdan; Rønningen, Torunn; Burlacu, Alexandrina; Simionescu, Maya; Moskaug, Jan Øivind; Valen, Guro

    2014-08-01

    Cardioprotection can be evoked through extracardiac approaches. This prompted us to investigate whether remote transplantation of stem cells confers protection of the heart against ischemic injury. The cardioprotective effect of subcutaneous transplantation of naïve versus heme oxygenase-1 (HMOX-1)-overexpressing mouse mesenchymal stem cells (MSC) to mice was investigated in hearts subjected to ischemia-reperfusion in a Langendorff perfusion system. Mice were transplanted into the interscapular region with naïve or HMOX-1 transfected MSC isolated from transgenic luciferase reporter mice and compared to sham-treated animals. The fate of transplanted cells was followed by in vivo bioluminescence imaging, revealing that MSC proliferated, but did not migrate detectably from the injection site. Ex vivo analysis of the hearts showed that remote transplantation of mouse adipose-derived MSC (mASC) resulted in smaller infarcts and improved cardiac function after ischemia-reperfusion compared to sham-treated mice. Although HMOX-1 overexpression conferred cytoprotective effects on mASC against oxidative stress in vitro, no additive beneficial effect of HMOX-1 transfection was noted on the ischemic heart. Subcutaneous transplantation of MSC also improved left ventricular function when transplanted in vivo after myocardial infarction. Plasma analysis and gene expression profile of naïve- and HMOX-1-mASC after transplantation pointed toward pentraxin 3 as a possible factor involved in the remote cardioprotective effect of mASC. These results have significant implications for understanding the behavior of stem cells after transplantation and development of safe and noninvasive cellular therapies with clinical applications. Remote transplantation of MSC can be considered as an alternative procedure to induce cardioprotection. © 2014 AlphaMed Press.

  6. Optimized Heart Sampling and Systematic Evaluation of Cardiac Therapies in Mouse Models of Ischemic Injury: Assessment of Cardiac Remodeling and Semi-Automated Quantification of Myocardial Infarct Size.

    Science.gov (United States)

    Valente, Mariana; Araújo, Ana; Esteves, Tiago; Laundos, Tiago L; Freire, Ana G; Quelhas, Pedro; Pinto-do-Ó, Perpétua; Nascimento, Diana S

    2015-12-02

    Cardiac therapies are commonly tested preclinically in small-animal models of myocardial infarction. Following functional evaluation, post-mortem histological analysis is essential to assess morphological and molecular alterations underlying the effectiveness of treatment. However, non-methodical and inadequate sampling of the left ventricle often leads to misinterpretations and variability, making direct study comparisons unreliable. Protocols are provided for representative sampling of the ischemic mouse heart followed by morphometric analysis of the left ventricle. Extending the use of this sampling to other types of in situ analysis is also illustrated through the assessment of neovascularization and cellular engraftment in a cell-based therapy setting. This is of interest to the general cardiovascular research community as it details methods for standardization and simplification of histo-morphometric evaluation of emergent heart therapies. © 2015 by John Wiley & Sons, Inc. Copyright © 2015 John Wiley & Sons, Inc.

  7. Cognitive behavioral therapy for depression in patients with heart failure: a critical review.

    Science.gov (United States)

    Dekker, Rebecca L

    2008-03-01

    Depression is a significant problem in patients with heart failure. Cognitive behavioral therapy (CBT) has been proposed as a potential non-pharmacological treatment for depression in patients with heart failure. The purpose of this review is to examine the evidence for the use of CBT in treating depression and depressive symptoms in patients with cardiovascular illness. In six of the ten studied reviewed, researchers found that CBT reduced depressive symptoms; however, the limitations of the studies prevent wide generalization of the results. There is insufficient evidence to support the use of CBT for the treatment of depressive symptoms in patients with cardiovascular illness at this time. Large randomized, controlled trials that demonstrate the efficacy of CBT are needed before nurses routinely refer patients with heart failure to CBT for the purpose of improving depression or depressive symptoms.

  8. Techniques for Identification of Left Ventricular Asynchrony for Cardiac Resynchronization Therapy in Heart Failure

    Directory of Open Access Journals (Sweden)

    Peter Schuster

    2005-07-01

    Full Text Available The most recent treatment option of medically refractory heart failure includes cardiac resynchronization therapy (CRT by biventricular pacing in selected patients in NYHA functional class III or IV heart failure. The widely used marker to indicate left ventricular (LV asynchrony has been the surface ECG, but seems not to be a sufficient marker of the mechanical events within the LV and prediction of clinical response. This review presents an overview of techniques for identification of left ventricular intra- and interventricular asynchrony. Both manuscripts for electrical and mechanical asynchrony are reviewed, partly predicting response to CRT. In summary there is still no gold standard for assessment of LV asynchrony for CRT, but both traditional and new echocardiographic methods have shown asynchronous LV contraction in heart failure patients, and resynchronized LV contraction during CRT and should be implemented as additional methods for selecting patients to CRT.

  9. Newer Therapies for Management of Stable Ischemic Heart Disease With Focus on Refractory Angina.

    Science.gov (United States)

    Singh, Mukesh; Arora, Rohit

    Ischemic heart disease remains a major public health problem nationally and internationally. Stable ischemic heart disease (SIHD) is one of the clinical manifestations of ischemic heart disease and is generally characterized by episodes of reversible myocardial demand/supply mismatch, related to ischemia or hypoxia, which are usually inducible by exercise, emotion, or other stress and reproducible-but which may also be occurring spontaneously. Improvements in the treatment of acute coronary syndromes along with increasing prevalence of cardiovascular risk factors, including diabetes and obesity, have led to increasing population of patients with SIHD. A significant number of these continue to have severe angina despite medical management and revascularization procedures performed and may progress to refractory angina. This article reviews the newer therapies in the treatment of SIHD with special focus in treating patients with refractory angina.

  10. Initial use of endothelial progenitor cells capturing stents in paediatric congenital heart disease.

    Science.gov (United States)

    Cabanelas, Nuno; Martins, José D F; Pinto, Fátima

    2014-10-01

    Stenosis, mediated by neointimal hyperplasia and thrombosis, is a major limiting factor in successful stent implantation. The introduction of a stent, coated in its endoluminal surface by antihuman CD34 antibodies with endothelial progenitor cell-capturing properties, opens the possibility of promoting a rapid and normal functioning coverage by endothelium and thus avoids both an excessive cell proliferation within stent and the need for long-term dual antiplatelet therapy. These stents, developed for adult coronary artery disease, have not yet been implanted in children or in those with congenital heart disease. In this paper, we describe the implantation of Genous® stents in three children with cyanotic congenital heart disease and obstructed systemic-to-pulmonary shunts. We describe the use of this stent and address its potential feasibility in paediatric congenital heart disease. To maintain the patency of two modified Blalock-Taussig shunts and one ductus arteriosus, four Genous® stents were implanted in three infants with cyanotic heart disease. All procedures were immediately successful, with resolution of stenosis and improvement in transcutaneous oxygen saturation from 66% ± 3.6% to 92% ± 2.6%. In the follow-up, one stent had no occlusion; however, the remaining two had partial occlusion after 5 and 5.5 months, which were successfully managed with balloon dilatation preceding elective definitive surgical correction. In our preliminary experience, we demonstrated that Genous® stent implantation was feasible in infants with complex congenital heart disease. Additional studies with larger samples and longer follow-up are required to confirm the potential benefits of this technology in this clinical setting.

  11. Clinical Benefits of Stem Cells for Chronic Symptomatic Systolic Heart Failure: A Systematic Review of the Existing Data and Ongoing Trials.

    Science.gov (United States)

    Poulin, Marie-France; Deka, Anjan; Mohamedali, Burhan; Schaer, Gary L

    2016-11-01

    The benefits of stem cell therapy for patients with chronic symptomatic systolic heart failure due to ischemic and nonischemic cardiomyopathy (ICM and NICM, respectively) are unclear. We performed a systematic review of major published and ongoing trials of stem cell therapy for systolic heart failure and compared measured clinical outcomes for both types of cardiomyopathy. The majority of the 29 published studies demonstrated clinical benefits of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs). Left ventricular ejection fraction (LVEF) was improved in the majority of trials after therapy. Cell delivery combined with coronary artery bypass grafting was associated with the greatest improvement in LVEF. Left ventricular end-systolic volume (or diameter), New York Heart Association functional classification, quality of life, and exercise capacity were also improved in most studies after cell therapy. Most ICM trials demonstrated a significant improvement in perfusion defects, infarct size, and myocardial viability. Several larger clinical trials that are in progress employ alternative delivery modes, cell types, and longer follow-up periods. Stem cells are a promising therapeutic modality for patients with heart failure due to ICM or NICM. More data are required from larger blinded trials to determine which combination of cell type and delivery mode will yield the most benefit with avoidance of harm in these patient populations.

  12. Cell therapy worldwide: an incipient revolution.

    Science.gov (United States)

    Rao, Mahendra; Mason, Chris; Solomon, Susan

    2015-01-01

    The regenerative medicine field is large, diverse and active worldwide. A variety of different organizational and product models have been successful, and pioneering entrepreneurs have shown both what can work and, critically, what does not. Evolving regulations, novel funding mechanisms combined with new technological breakthroughs are keeping the field in a state of flux. The field struggles to cope with the lack of infrastructure and investment, it nevertheless has evolved from its roots in human stem cell therapy and tissue and organ transplants to a field composed of a variety of products from multiple cell sources with approval for use in numerous countries. Currently, tens of thousands of patients have been treated with some kind of cell therapy.

  13. Single-Cell Resolution of Temporal Gene Expression during Heart Development.

    Science.gov (United States)

    DeLaughter, Daniel M; Bick, Alexander G; Wakimoto, Hiroko; McKean, David; Gorham, Joshua M; Kathiriya, Irfan S; Hinson, John T; Homsy, Jason; Gray, Jesse; Pu, William; Bruneau, Benoit G; Seidman, J G; Seidman, Christine E

    2016-11-21

    Activation of complex molecular programs in specific cell lineages governs mammalian heart development, from a primordial linear tube to a four-chamber organ. To characterize lineage-specific, spatiotemporal developmental programs, we performed single-cell RNA sequencing of >1,200 murine cells isolated at seven time points spanning embryonic day 9.5 (primordial heart tube) to postnatal day 21 (mature heart). Using unbiased transcriptional data, we classified cardiomyocytes, endothelial cells, and fibroblast-enriched cells, thus identifying markers for temporal and chamber-specific developmental programs. By harnessing these datasets, we defined developmental ages of human and mouse pluripotent stem-cell-derived cardiomyocytes and characterized lineage-specific maturation defects in hearts of mice with heterozygous mutations in Nkx2.5 that cause human heart malformations. This spatiotemporal transcriptome analysis of heart development reveals lineage-specific gene programs underlying normal cardiac development and congenital heart disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes

    Science.gov (United States)

    Senni, Michele; Paulus, Walter J.; Gavazzi, Antonello; Fraser, Alan G.; Díez, Javier; Solomon, Scott D.; Smiseth, Otto A.; Guazzi, Marco; Lam, Carolyn S. P.; Maggioni, Aldo P.; Tschöpe, Carsten; Metra, Marco; Hummel, Scott L.; Edelmann, Frank; Ambrosio, Giuseppe; Stewart Coats, Andrew J.; Filippatos, Gerasimos S.; Gheorghiade, Mihai; Anker, Stefan D.; Levy, Daniel; Pfeffer, Marc A.; Stough, Wendy Gattis; Pieske, Burkert M.

    2014-01-01

    The management of heart failure with reduced ejection fraction (HF-REF) has improved significantly over the last two decades. In contrast, little or no progress has been made in identifying evidence-based, effective treatments for heart failure with preserved ejection fraction (HF-PEF). Despite the high prevalence, mortality, and cost of HF-PEF, large phase III international clinical trials investigating interventions to improve outcomes in HF-PEF have yielded disappointing results. Therefore, treatment of HF-PEF remains largely empiric, and almost no acknowledged standards exist. There is no single explanation for the negative results of past HF-PEF trials. Potential contributors include an incomplete understanding of HF-PEF pathophysiology, the heterogeneity of the patient population, inadequate diagnostic criteria, recruitment of patients without true heart failure or at early stages of the syndrome, poor matching of therapeutic mechanisms and primary pathophysiological processes, suboptimal study designs, or inadequate statistical power. Many novel agents are in various stages of research and development for potential use in patients with HF-PEF. To maximize the likelihood of identifying effective therapeutics for HF-PEF, lessons learned from the past decade of research should be applied to the design, conduct, and interpretation of future trials. This paper represents a synthesis of a workshop held in Bergamo, Italy, and it examines new and emerging therapies in the context of specific, targeted HF-PEF phenotypes where positive clinical benefit may be detected in clinical trials. Specific considerations related to patient and endpoint selection for future clinical trials design are also discussed. PMID:25104786

  15. Mesenchymal stromal cell therapy in ischemic stroke

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2016-11-01

    Full Text Available Ye Zhang, Hong Deng, Chao Pan, Yang Hu, Qian Wu, Na Liu, Zhouping Tang Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China Abstract: Stroke is a clinical disease with high incidence, high disability rate, and high mortality. But effective and safe therapy for stroke remains limited. Adult mesenchymal stromal cells (MSCs perform a variety of therapeutic functions. MSC delivery improves neurological outcomes in ischemic stroke models via neurorestorative and neuroprotective effects such as angiogenic effects, promoting endogenous proliferation, and reducing apoptosis and inflammation. MSC secretome also showed powerful therapeutic effects as a cell-based therapy in animal experiments. Several clinical trials on MSC implantation via different routes have now been completed in patients with stroke. Although challenges such as immunogenicity of allo-MSCs and large-scale production strategies need to be overcome, MSCs can be considered as a promising potential therapy for ischemic stroke. Keywords: mesenchymal stromal cell, stroke, therapy, transplantation, exosomes

  16. The Role of Ozone Therapy in Neurohumoral Regulation in Patients with Ischemic Heart Diseases

    Directory of Open Access Journals (Sweden)

    Elena I. Sycheva

    2012-11-01

    Full Text Available Diseases, caused by atherosclerosis, first of all, ischemic heart disease are major cause of mortality in many countries, including Russia. Despite the different existing theories of atherosclerosis formation, pathogeny of this disease is mainly connected with lipid storage disease, blood rheological properties, activation of lipid peroxidation. Ozone therapy is one of the upcoming trends of preventive medicine. The findings of its application in the course of resort treatment showed homeostasis indicators improvement, which can serve as a basis for ozone therapy application in the course of multiple-factor treatment and prevention of cardiovascular diseases in patients.

  17. Combination decongestion therapy in hospitalized heart failure: loop diuretics, mineralocorticoid receptor antagonists and vasopressin antagonists.

    Science.gov (United States)

    Vaduganathan, Muthiah; Mentz, Robert J; Greene, Stephen J; Senni, Michele; Sato, Naoki; Nodari, Savina; Butler, Javed; Gheorghiade, Mihai

    2015-01-01

    Congestion is the most common reason for admissions and readmissions for heart failure (HF). The vast majority of hospitalized HF patients appear to respond readily to loop diuretics, but available data suggest that a significant proportion are being discharged with persistent evidence of congestion. Although novel therapies targeting congestion should continue to be developed, currently available agents may be utilized more optimally to facilitate complete decongestion. The combination of loop diuretics, natriuretic doses of mineralocorticoid receptor antagonists and vasopressin antagonists represents a regimen of currently available therapies that affects early and persistent decongestion, while limiting the associated risks of electrolyte disturbances, hemodynamic fluctuations, renal dysfunction and mortality.

  18. Duchenne muscular dystrophy: current cell therapies.

    Science.gov (United States)

    Sienkiewicz, Dorota; Kulak, Wojciech; Okurowska-Zawada, Bożena; Paszko-Patej, Grażyna; Kawnik, Katarzyna

    2015-07-01

    Duchenne muscular dystrophy is a genetically determined X-linked disease and the most common, progressive pediatric muscle disorder. For decades, research has been conducted to find an effective therapy. This review presents current therapeutic methods for Duchenne muscular dystrophy, based on scientific articles in English published mainly in the period 2000 to 2014. We used the PubMed database to identify and review the most important studies. An analysis of contemporary studies of stem cell therapy and the use of granulocyte colony-stimulating factor (G-CSF) in muscular dystrophy was performed.

  19. Cell therapy for the degenerating intervertebral disc.

    Science.gov (United States)

    Tong, Wei; Lu, Zhouyu; Qin, Ling; Mauck, Robert L; Smith, Harvey E; Smith, Lachlan J; Malhotra, Neil R; Heyworth, Martin F; Caldera, Franklin; Enomoto-Iwamoto, Motomi; Zhang, Yejia

    2017-03-01

    Spinal conditions related to intervertebral disc (IVD) degeneration cost billions of dollars in the US annually. Despite the prevalence and soaring cost, there is no specific treatment that restores the physiological function of the diseased IVD. Thus, it is vital to develop new treatment strategies to repair the degenerating IVD. Persons with IVD degeneration without back pain or radicular leg pain often do not require any intervention. Only patients with severe back pain related to the IVD degeneration or biomechanical instability are likely candidates for cell therapy. The IVD progressively degenerates with age in humans, and strategies to repair the IVD depend on the stage of degeneration. Cell therapy and cell-based gene therapy aim to address moderate disc degeneration; advanced stage disease may require surgery. Studies involving autologous, allogeneic, and xenogeneic cells have all shown good survival of these cells in the IVD, confirming that the disc niche is an immunologically privileged site, permitting long-term survival of transplanted cells. All of the animal studies reviewed here reported some improvement in disc structure, and 2 studies showed attenuation of local inflammation. Among the 50 studies reviewed, 25 used some type of scaffold, and cell leakage is a consistently noted problem, though some studies showed reduced cell leakage. Hydrogel scaffolds may prevent cell leakage and provide biomechanical support until cells can become established matrix producers. However, these gels need to be optimized to prevent this leakage. Many animal models have been leveraged in this research space. Rabbit is the most frequently used model (28 of 50), followed by rat, pig, and dog. Sheep and goat IVDs resemble those of humans in size and in the absence of notochordal cells. Despite this advantage, there were only 2 sheep and 1 goat studies of 50 studies in this cohort. It is also unclear if a study in large animals is needed before clinical trials since

  20. Mesenchymal bone marrow cell therapy in a mouse model of chagas disease. Where do the cells go?

    Directory of Open Access Journals (Sweden)

    Jasmin

    Full Text Available Chagas disease, resulting from infection with the parasite Trypanosoma cruzi (T. cruzi, is a major cause of cardiomyopathy in Latin America. Drug therapy for acute and chronic disease is limited. Stem cell therapy with bone marrow mesenchymal cells (MSCs has emerged as a novel therapeutic option for cell death-related heart diseases, but efficacy of MSC has not been tested in Chagas disease.We now report the use of cell-tracking strategies with nanoparticle labeled MSC to investigate migration of transplanted MSC in a murine model of Chagas disease, and correlate MSC biodistribution with glucose metabolism and morphology of heart in chagasic mice by small animal positron emission tomography (microPET. Mice were infected intraperitoneally with trypomastigotes of the Brazil strain of T. cruzi and treated by tail vein injection with MSC one month after infection. MSCs were labeled with near infrared fluorescent nanoparticles and tracked by an in vivo imaging system (IVIS. Our IVIS results two days after transplant revealed that a small, but significant, number of cells migrated to chagasic hearts when compared with control animals, whereas the vast majority of labeled MSC migrated to liver, lungs and spleen. Additionally, the microPET technique demonstrated that therapy with MSC reduced right ventricular dilation, a phenotype of the chagasic mouse model.We conclude that the beneficial effects of MSC therapy in chagasic mice arise from an indirect action of the cells in the heart rather than a direct action due to incorporation of large numbers of transplanted MSC into working myocardium.

  1. Mortality risk of long-term amiodarone therapy for atrial fibrillation patients without structural heart disease.

    Science.gov (United States)

    Qin, Dingxin; Leef, George; Alam, Mian Bilal; Rattan, Rohit; Munir, Mohamad Bilal; Patel, Divyang; Khattak, Furqan; Adelstein, Evan; Jain, Sandeep K; Saba, Samir

    2015-01-01

    Amiodarone is often prescribed in the management of atrial fibrillation (AF) but is known to cause significant end-organ toxicities. In this study, we examined the impact of amiodarone on all-cause mortality in AF patients with structurally normal hearts. We performed a retrospective cohort analysis of all AF patients with structurally normal hearts who were prescribed antiarrhythmic drugs (AAD) for rhythm control of AF at our institution from 2006 to 2013 (n = 2,077). Baseline differences between the amiodarone (AMIO: n = 403) and other AADs (NON-AMIO: n = 1,674) groups were corrected for using propensity score matching. Amiodarone use as first-line therapy decreased significantly with a higher degree of prescriber specialization in arrhythmia management (31%, 22%, and 9% for primary care physicians, general cardiologists and cardiac electrophysiologists, respectively, p amiodarone was associated with increased all-cause (HR 2.41, p = 0.012) and non-cardiac (HR 3.55, p = 0.008) mortality, but not cardiac mortality. AF recurrence and cardiac hospitalizations were similar between the two study groups. Amiodarone treatment of AF is associated with increased mortality in patients without structural heart disease and therefore should be avoided or only used as a second-line therapy, when other AF therapies fail. Adherence to guideline recommendations in the management of AF patients impacts clinical outcome.

  2. Adult Stem Cell Therapy for Stroke: Challenges and Progress

    Science.gov (United States)

    Bang, Oh Young; Kim, Eun Hee; Cha, Jae Min; Moon, Gyeong Joon

    2016-01-01

    Stroke is one of the leading causes of death and physical disability among adults. It has been 15 years since clinical trials of stem cell therapy in patients with stroke have been conducted using adult stem cells like mesenchymal stem cells and bone marrow mononuclear cells. Results of randomized controlled trials showed that adult stem cell therapy was safe but its efficacy was modest, underscoring the need for new stem cell therapy strategies. The primary limitations of current stem cell therapies include (a) the limited source of engraftable stem cells, (b) the presence of optimal time window for stem cell therapies, (c) inherited limitation of stem cells in terms of growth, trophic support, and differentiation potential, and (d) possible transplanted cell-mediated adverse effects, such as tumor formation. Here, we discuss recent advances that overcome these hurdles in adult stem cell therapy for stroke. PMID:27733032

  3. Stem cell-based photodynamic therapy.

    Science.gov (United States)

    Shrestha, Tej B; Seo, Gwi M; Basel, Matthew T; Kalita, Mausam; Wang, Hongwang; Villanueva, David; Pyle, Marla; Balivada, Sivasai; Rachakatla, Raja Shekar; Shinogle, Heather; Thapa, Prem S; Moore, David; Troyer, Deryl L; Bossmann, Stefan H

    2012-07-01

    We have transfected murine neural stem cells (NSCs) and rat umbilical cord matrix-derived stem cells (RUCMSCs) with a plasmid expressing gaussia luciferase (gLuc). These cells are engineered to secrete the luciferase. We have used gLuc containing supernatant from culturing the NSCs to perform in vitro photodynamic therapy of murine melanoma cells (B16F10), and RUCMSCs to perform in vivo PDT of lung melanomas in C57BL/6 mice. The treatment system was comprised of aminolevulic acid as a prodrug for the synthesis of the photosensitizer protoporphyrin IX, gaussia luciferase, and its' substrate coelenterazine. A significant reduction of the number of live melanoma cells in vitro and a borderline significant retardation of tumour growth in vivo was observed after coelenterazine-mediated PDT.

  4. Targeted Therapy for Renal Cell Carcinoma.

    Science.gov (United States)

    Joshi, R; Rawal, S

    2015-01-01

    Our study aims to evaluate the use of targeted therapy in metastatic renal cell carcinoma Methods: This is a prospective study done over three years from December 2010 to December, 2013.Out of Forty seven patients of metastatic renal cell carcinoma 8(neo-adjuvant cases) were excluded and 39 were included in this study. All patients received Tyrosine kinase inhibitor, sunitinib therapy (50 mg OD, 4/2 scheme). All 39 patients underwent radical nephrectomy prior to sunitinib therapy. Patients were followed up every cycle for their clinical symptoms following sunitinib therapy and every 3 months with chest X-ray, ultra-sonography and bone scan. CT scan was done if needed. A RECIST criterion was used to evaluate the complete, partial and no tumor response. The median survival was 28.5 months (CI 9.253-47.7) and progression free survival (PFS) was 9.16 months(CI 6.08-12.23).According to RECIST, stable disease was found in 6 patients till date and a complete response in two patients. Clear cell histology was found in 30(76.9%) patients, papillary variety in 6(15.39%) patients, chromophobe type was seen in one patient and rest had mixed sarcomatoid papillary and rhabdoid clear cell variety. Twenty four patients (61.5%) had multiple metastases. Most frequent metastasis was seen in lungs in 14 patients (36%) and bone in 12 patients (31%).Metastases were also seen in draining lymph nodes, adrenals, omentum,skin, liver, and brain. In our cohort, use of sunitinib showed similar outcome to previously published articles. Our study supports the use of sunitinib in metastatic renal cell carcinoma.

  5. Cost-Effectiveness of Adding Cardiac Resynchronization Therapy to an Implantable Cardioverter-Defibrillator Among Patients With Mild Heart Failure

    DEFF Research Database (Denmark)

    Woo, Christopher Y; Strandberg, Erika J; Schmiegelow, Michelle D

    2015-01-01

    -defibrillator (ICD) alone among patients with left ventricular systolic dysfunction, prolonged intraventricular conduction, and mild heart failure. DESIGN: Markov decision model. DATA SOURCES: Clinical trials, clinical registries, claims data from Centers for Medicare & Medicaid Services, and Centers for Disease......BACKGROUND: Cardiac resynchronization therapy (CRT) reduces mortality and heart failure hospitalizations in patients with mild heart failure. OBJECTIVE: To estimate the cost-effectiveness of adding CRT to an implantable cardioverter-defibrillator (CRT-D) compared with implantable cardioverter...

  6. Cardiac resynchronisation therapy in paediatric and congenital heart disease : differential effects in various anatomical and functional substrates

    NARCIS (Netherlands)

    Janousek, J.; Gebauer, R. A.; Abdul-Khaliq, H.; Turner, M.; Kornyei, L.; Grollmuss, O.; Rosenthal, E.; Villain, E.; Frueh, A.; Paul, T.; Blom, N. A.; Happonen, J-M; Bauersfeld, U.; Jacobsen, J. R.; van den Heuvel, F.; Delhaas, T.; Papagiannis, J.; Trigo, C.

    2009-01-01

    Background: Cardiac resynchronisation therapy (CRT) is increasingly used in children in a variety of anatomical and pathophysiological conditions, but published data are scarce. Objective: To record current practice and results of CRT in paediatric and congenital heart disease. Design: Retrospective

  7. Quality of Life with Defibrillator Therapy or Amiodarone in Heart Failure

    Science.gov (United States)

    Mark, Daniel B.; Anstrom, Kevin J.; Sun, Jie L.; Clapp-Channing, Nancy E.; Tsiatis, Anastasios A.; Davidson-Ray, Linda; Lee, Kerry L.; Bardy, Gust H.

    2010-01-01

    Background Implantable cardioverter defibrillator (ICD) therapy significantly prolongs life in patients at increased risk of sudden cardiac death from depressed left ventricular function. However, it is unclear whether this increased longevity is accompanied by deterioration in quality of life. Methods The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) compared ICD therapy or amiodarone versus state-of-the-art medical therapy alone in 2521 stable heart failure patients with depressed left ventricular function. Quality of life, a secondary end point of the trial, was prospectively measured at baseline, 3, 12, and 30 months and was 93% to 98% complete. The Duke Activity Status Index (which measures cardiac physical functioning) and the SF-36 Mental Health Inventory (which measures psychological well-being or distress) were prespecified principal quality-of-life outcomes. Multiple additional quality-of-life outcomes were also examined. Results Compared with medical therapy alone, psychological well-being in the ICD arm significantly improved at 3 months (p=0.01) and 12 months (p=0.004) but not at 30 months. No clinically or statistically significant differences in physical functioning by treatment were observed. Some other quality-of-life measures improved in the ICD arm at 3 and/or 12 months but none differed significantly at 30 months. ICD shocks within the month preceding a scheduled assessment were associated with decreased quality of life in multiple domains. Amiodarone had no significant effects on the principal quality-of-life outcomes. Conclusions In a large primary prevention population with moderately symptomatic heart failure, single lead ICD therapy was not associated with any detectable adverse quality-of-life effects over 30 months of follow-up. PMID:18768943

  8. PET imaging of adoptive progenitor cell therapies.

    Energy Technology Data Exchange (ETDEWEB)

    Gelovani, Juri G.

    2008-05-13

    Objectives. The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive “tracking” of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to

  9. Stem Cell Therapy for Degenerative Disc Disease

    Directory of Open Access Journals (Sweden)

    Doniel Drazin

    2012-01-01

    Full Text Available Low back pain is widely recognized as one of the most prevalent pathologies in the developed world. In the United States, low back pain is the most common health problem for adults under the age of 50, resulting in significant societal and personal costs. While the causes of low back pain are myriad, it has been significantly associated with intervertebral disc (IVD degeneration. Current first-line therapies for IVD degeneration such as physical therapy and spinal fusion address symptoms, but do not treat the underlying degeneration. The use of tissue engineering to treat IVD degeneration provides an opportunity to correct the pathological process. Novel techniques are currently being investigated and have shown mixed results. One major avenue of investigation has been stem cell injections. Mesenchymal stem cells (MSCs have shown promise in small animal models, but results in larger vertebrates have been mixed.

  10. Renal Preservation Therapy for Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Yichun Chiu

    2012-01-01

    Full Text Available Renal preservation therapy has been a promising concept for the treatment of localized renal cell carcinoma (RCC for 20 years. Nowadays partial nephrectomy (PN is well accepted to treat the localized RCC and the oncological control is proved to be the same as the radical nephrectomy (RN. Under the result of well oncological control, minimal invasive method gains more popularity than the open PN, like laparoscopic partial nephrectomy (LPN and robot assisted laparoscopic partial nephrectomy (RPN. On the other hand, thermoablative therapy and cryoablation also play an important role in the renal preservation therapy to improve the patient procedural tolerance. Novel modalities, but limited to small number of patients, include high-intensity ultrasound (HIFU, radiosurgery, microwave therapy (MWT, laser interstitial thermal therapy (LITT, and pulsed cavitational ultrasound (PCU. Although initial results are encouraging, their real clinical roles are still under evaluation. On the other hand, active surveillance (AS has also been advocated by some for patients who are unfit for surgery. It is reasonable to choose the best therapeutic method among varieties of treatment modalities according to patients' age, physical status, and financial aid to maximize the treatment effect among cancer control, patient morbidity, and preservation of renal function.

  11. Large animal models for stem cell therapy.

    Science.gov (United States)

    Harding, John; Roberts, R Michael; Mirochnitchenko, Oleg

    2013-03-28

    The field of regenerative medicine is approaching translation to clinical practice, and significant safety concerns and knowledge gaps have become clear as clinical practitioners are considering the potential risks and benefits of cell-based therapy. It is necessary to understand the full spectrum of stem cell actions and preclinical evidence for safety and therapeutic efficacy. The role of animal models for gaining this information has increased substantially. There is an urgent need for novel animal models to expand the range of current studies, most of which have been conducted in rodents. Extant models are providing important information but have limitations for a variety of disease categories and can have different size and physiology relative to humans. These differences can preclude the ability to reproduce the results of animal-based preclinical studies in human trials. Larger animal species, such as rabbits, dogs, pigs, sheep, goats, and non-human primates, are better predictors of responses in humans than are rodents, but in each case it will be necessary to choose the best model for a specific application. There is a wide spectrum of potential stem cell-based products that can be used for regenerative medicine, including embryonic and induced pluripotent stem cells, somatic stem cells, and differentiated cellular progeny. The state of knowledge and availability of these cells from large animals vary among species. In most cases, significant effort is required for establishing and characterizing cell lines, comparing behavior to human analogs, and testing potential applications. Stem cell-based therapies present significant safety challenges, which cannot be addressed by traditional procedures and require the development of new protocols and test systems, for which the rigorous use of larger animal species more closely resembling human behavior will be required. In this article, we discuss the current status and challenges of and several major directions

  12. Experimental myocardial stem cell therapy for ST-elevation myocardial infarction

    DEFF Research Database (Denmark)

    Kastrup, Jens; Mygind, Naja D; Qayyum, Abbas A

    2016-01-01

    ), chronic IHD and heart failure. The patients suffer from chest pain (angina), dyspnea and a reduced quality of life. Common for all these conditions is loss of functional cardiomyocytes and endothelial cells. Stem cell therapy to regenerate injured myocardium is a new treatment option which has gained much...... interest in the last 10-15 years especially after STEMI. Many preclinical and clinical studies have shown encouraging results but also very diverse clinical outcomes after stem cell treatment. This diversity in results may be explained by different factors, such as cell isolation technique, infarct...... location, timing and route of delivery, cell dosage, cell type etc. The present review will try to elaborate and clarify the present status for stem cell therapy in STEMI....

  13. Cell-based therapy for kidney disease

    OpenAIRE

    Chung, Hyun Chul; Ko, In Kap; Atala, Anthony; Yoo, James J.

    2015-01-01

    The prevalence of renal disease continues to increase worldwide. When normal kidney is injured, the damaged renal tissue undergoes pathological and physiological events that lead to acute and chronic kidney diseases, which frequently progress to end stage renal failure. Current treatment of these renal pathologies includes dialysis, which is incapable of restoring full renal function. To address this issue, cell-based therapy has become a potential therapeutic option to treat renal pathologie...

  14. Aerobic Exercise and Pharmacological Therapies for Skeletal Myopathy in Heart Failure: Similarities and Differences

    Directory of Open Access Journals (Sweden)

    Aline V. Bacurau

    2016-01-01

    Full Text Available Skeletal myopathy has been identified as a major comorbidity of heart failure (HF affecting up to 20% of ambulatory patients leading to shortness of breath, early fatigue, and exercise intolerance. Neurohumoral blockade, through the inhibition of renin angiotensin aldosterone system (RAS and β-adrenergic receptor blockade (β-blockers, is a mandatory pharmacological therapy of HF since it reduces symptoms, mortality, and sudden death. However, the effect of these drugs on skeletal myopathy needs to be clarified, since exercise intolerance remains in HF patients optimized with β-blockers and inhibitors of RAS. Aerobic exercise training (AET is efficient in counteracting skeletal myopathy and in improving functional capacity and quality of life. Indeed, AET has beneficial effects on failing heart itself despite being of less magnitude compared with neurohumoral blockade. In this way, AET should be implemented in the care standards, together with pharmacological therapies. Since both neurohumoral inhibition and AET have a direct and/or indirect impact on skeletal muscle, this review aims to provide an overview of the isolated effects of these therapeutic approaches in counteracting skeletal myopathy in HF. The similarities and dissimilarities of neurohumoral inhibition and AET therapies are also discussed to identify potential advantageous effects of these combined therapies for treating HF.

  15. Exploiting tumor cell senescence in anticancer therapy

    Science.gov (United States)

    Lee, Minyoung; Lee, Jae-Seon

    2014-01-01

    Cellular senescence is a physiological process of irreversible cell-cycle arrest that contributes to various physiological and pathological processes of aging. Whereas replicative senescence is associated with telomere attrition after repeated cell division, stress-induced premature senescence occurs in response to aberrant oncogenic signaling, oxidative stress, and DNA damage which is independent of telomere dysfunction. Recent evidence indicates that cellular senescence provides a barrier to tumorigenesis and is a determinant of the outcome of cancer treatment. However, the senescence-associated secretory phenotype, which contributes to multiple facets of senescent cancer cells, may influence both cancer-inhibitory and cancer-promoting mechanisms of neighboring cells. Conventional treatments, such as chemo- and radiotherapies, preferentially induce premature senescence instead of apoptosis in the appropriate cellular context. In addition, treatment-induced premature senescence could compensate for resistance to apoptosis via alternative signaling pathways. Therefore, we believe that an intensive effort to understand cancer cell senescence could facilitate the development of novel therapeutic strategies for improving the efficacy of anticancer therapies. This review summarizes the current understanding of molecular mechanisms, functions, and clinical applications of cellular senescence for anticancer therapy. [BMB Reports 2014; 47(2): 51-59] PMID:24411464

  16. Allogeneic adipose stem cell therapy in acute myocardial infarction.

    Science.gov (United States)

    Rigol, Montserrat; Solanes, Núria; Roura, Santiago; Roqué, Mercè; Novensà, Laura; Dantas, Ana Paula; Martorell, Jaume; Sitges, Marta; Ramírez, José; Bayés-Genís, Antoni; Heras, Magda

    2014-01-01

    Stem cell therapy offers a promising approach to reduce the long-term mortality rate associated with heart failure after acute myocardial infarction (AMI). To date, in vivo translational studies have not yet fully studied the immune response to allogeneic adipose tissue-derived mesenchymal stem cells (ATMSCs). We analysed the immune response and the histological and functional effects of allogeneic ATMSCs in a porcine model of reperfused AMI and determine the effect of administration timing. Pigs that survived AMI (24/26) received intracoronary administration of culture medium after reperfusion (n = 6), ATMSCs after reperfusion (n = 6), culture medium 7 days after AMI (n = 6) or ATMSCs 7 days after AMI (n = 6). At 3-week follow-up, cardiac function, alloantibodies and histological analysis were evaluated. Administration of ATMSCs after reperfusion and 7 days after AMI resulted in similar rates of cell engraftment; some of those cells expressed endothelial, smooth muscle and cardiomyogenic cell lineage markers. Delivery of ATMSCs after reperfusion compared with that performed at 7 days was more effective in increasing: vascular density (249 ± 64 vs. 161 ± 37 vessels/mm2; P < 0.01), T lymphocytes (1 ± 0.4 vs. 0.4 ± 0.3% of area CD3(+) ; P < 0.05) and expression of vascular endothelial growth factor (VEGF; 32 ± 7% vs. 20 ± 4% of area VEGF(+) ; P < 0.01). Allogeneic ATMSC-based therapy did not change ejection fraction but generated alloantibodies. The present study is the first to demonstrate that allogeneic ATMSCs elicit an immune response and, when administered immediately after reperfusion, are more effective in increasing VEGF expression and neovascularization. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

  17. Incidence, time of occurrence and response to heart failure therapy in patients with anthracycline cardiotoxicity.

    Science.gov (United States)

    Khan, Arshad A; Ashraf, Asma; Singh, Rajinder; Rahim, Aadil; Rostom, Walid; Hussain, Mumtaz; Renner, Ian; Collins, Nicholas J

    2017-01-01

    Anthracyclines are commonly used chemotherapeutic medications. In the current analysis, we evaluated all-cause mortality and incidence, timing and response to medical therapy of anthracycline cardiotoxicity. Left ventricular ejection fraction (LVEF) was serially assessed using gated heart pool scan/echocardiography in patients receiving anthracycline-based chemotherapy from January 2009 to December 2014. A total of 1204 patients was administered anthracyclines during the study period. During a median follow up of 32 (interquartile range: 15-58) months, all-cause mortality was 38% (n = 463), with the incidence of cardiotoxicity 10.2% (n = 123). Only 15.4% (n = 19) patients required heart failure hospitalisation, with 48% (n = 59) of patients commenced on beta blockade therapy and/or angiotensin-converting enzyme inhibitors. The majority of patients (73.2%, n = 90) experienced cardiotoxicity within 1 year of anthracycline initiation. The proportion of patients with complete, partial and no LVEF recovery were 16.3% (n = 20), 29.3% (n = 36) and 54.4% (n = 67) respectively. Mortality was higher in the cardiotoxicity group (49% vs 37%, P < 0.01). History of coronary artery disease, leukaemia, idarubicin use and high cumulative anthracycline dose were predictors of cardiotoxicity. Cardiotoxicity after anthracycline use predictably occurs within the first year of therapy and is dose-related, with variable degrees of recovery. While the need for hospitalisation for heart failure was uncommon, medical therapy appears underutilised, suggesting there may be a role for improved surveillance and early initiation of treatment. © 2016 Royal Australasian College of Physicians.

  18. Potential and Limitation of HLA-Based Banking of Human Pluripotent Stem Cells for Cell Therapy

    Directory of Open Access Journals (Sweden)

    Casimir de Rham

    2014-01-01

    Full Text Available Great hopes have been placed on human pluripotent stem (hPS cells for therapy. Tissues or organs derived from hPS cells could be the best solution to cure many different human diseases, especially those who do not respond to standard medication or drugs, such as neurodegenerative diseases, heart failure, or diabetes. The origin of hPS is critical and the idea of creating a bank of well-characterized hPS cells has emerged, like the one that already exists for cord blood. However, the main obstacle in transplantation is the rejection of tissues or organ by the receiver, due to the three main immunological barriers: the human leukocyte antigen (HLA, the ABO blood group, and minor antigens. The problem could be circumvented by using autologous stem cells, like induced pluripotent stem (iPS cells, derived directly from the patient. But iPS cells have limitations, especially regarding the disease of the recipient and possible difficulties to handle or prepare autologous iPS cells. Finally, reaching standards of good clinical or manufacturing practices could be challenging. That is why well-characterized and universal hPS cells could be a better solution. In this review, we will discuss the interest and the feasibility to establish hPS cells bank, as well as some economics and ethical issues.

  19. New-onset heart failure in association with severe hypertension during trastuzumab therapy.

    Science.gov (United States)

    Herrmann, Joerg; Herrmann, Sandra M; Haddad, Tufia C

    2014-12-01

    Heart failure is a dreaded complication of trastuzumab therapy in women with breast cancer overexpressing the human epidermal growth factor receptor (HER)-2. Experimental studies have pointed out that the HER-2 signaling pathway is important in the adaptation to high afterload conditions and its inactivation leads to cardiac decompensation. Herein, we report on 2 patients with breast cancer who were receiving trastuzumab monotherapy and required hospital admission for new-onset heart failure. This occurred at a time of unprecedented blood pressure elevations, in one case due to cessation of antihypertensive medications and in the other case due to a scleroderma crisis. Although trastuzumab may not have been the precipitating factor for blood pressure dyscontrol in these patients, severe, uncontrolled hypertension may have been the precipitating factor for trastuzumab-related acute heart failure. These 2 cases add to previous reports recognizing systemic hypertension as a risk factor for the development of trastuzumab cardiotoxicity and translate experimental observations of the significance of the HER-2 signaling pathway to the bedside. Pending further confirmation, the present observations may raise awareness of the need for appropriate monitoring and control of systemic hypertension in patients receiving trastuzumab, or potentially any other HER-2-targeted therapy. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  20. Advances in interventional and hybrid therapy in neonatal congenital heart disease.

    Science.gov (United States)

    Schranz, Dietmar; Michel-Behnke, Ina

    2013-10-01

    In addition to the considerable surgical advances in treating congenital heart diseases, hybrid and transcatheter therapies have become a cornerstone of neonatal cardiology within the last decade. Approaches to the care of cyanotic newborns with congenital heart disease focused on manipulations of the inter-atrial septum, right ventricular outflow tract obstructions, and on the arterial duct as the source for pulmonary blood flow. Currently, fewer interventional procedures are used in newborns and small infants to treat excessive pulmonary blood flow caused by shunt lesions, but transcatheter techniques and hybrid strategies have been developed to treat newborns suffering from inadequate systemic perfusion. However, transcatheter techniques are still not available to treat failing systemic ventricles without obvious structural disorders of the myocardium or dilated cardiomyopathies in newborns and infancy, despite new surgical-interventional strategies are already developed to avoid or to delay early heart transplantation. In conclusion, material and technical improvements have enabled transcatheter techniques to replace medical-based therapies to solve structurally dependent cardiovascular diseases. However, evidence-based and long-term follow-up data are required. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. EVALUATION CARDIAC RESYNCHRONIZATION THERAPY IN PATIENTS WITH CHRONIC ISCHEMIC HEART FAILURE

    Directory of Open Access Journals (Sweden)

    A. J. Fishman

    2011-01-01

    Full Text Available Objective — studying dyssynchrony characteristics and evaluation correction effectiveness in patients with chronic heart failure (CHF of ischemic origin.Materials and methods. The study included 125 patients with chronic heart failure of ischemic etiology, 28 of them — with coronary heart disease (CHD who had undergone aorto-and / or mammarokoronary bypass and / or percutaneous coronary intervention, 42 — with coronary artery disease and postinfarction cardiosclerosis, 32 — with arrhythmic variant of coronary artery disease, 23 — with stable angina without evidence of arrhythmia. Among included patients, biventricular pacemakers were implanted for 17 patients. All patients underwent echocardiography with determination of the parameters of dyssynchrony.Results and conclusion. Among patients with CHF ischemic symptoms dyssynchrony was diagnosed in 36 (28.8 % cases. Statistically significant association between patients with cardiac arrhythmias and dyssynchrony was determined. At the same time the incidence of dyssynchrony was not associated with various forms of ischemic heart disease, and did not depend on the anamnesis of cardiac surgery. Dependence of the frequency of occurrence of dyssynchrony on the severity of CHF was revealed. Patients selected for implantation of biventricular pacemakers, especially in view of echocardiographic signs of dyssynchrony had significant improvement after providing cardiac resynchronization therapy. Effect of the treatment does not depend on the atrial fibrillation rhythm presence.

  2. Self-management of oral anticoagulant therapy for mechanical heart valve patients

    DEFF Research Database (Denmark)

    Christensen, Thomas D; Attermann, Jørn; Pilegaard, Hans K

    2001-01-01

    of self-management of OAT in patients with mechanical heart valve prostheses on a 4-year perspective in a prospective, non-randomized study. Design: Twenty-four patients with mechanical heart valves and on self-managed OAT were followed for up to 4 years. A matched, retrospectively selected group.......4%–2.9%) for the control group. Conclusion: Self-management of OAT is a feasible and safe concept for selected patients with mechanical heart valve prostheses also on a long-term basis. It provides at least as good and most likely better quality of anticoagulant therapy than conventional management assessed by time within...... of conventionally managed heart valve patients (control group) was used as reference. Results: The median observation time was 1175 days (range: 174–1428 days). The self-managed patients were within therapeutic INR target range for a mean of 78.0% (range: 36.1%–93.9%) of the time compared with 61.0% (range 37...

  3. Efficacy and safety of carvedilol in patients with chronic heart failure receiving concomitant amiodarone therapy. Australia/New Zealand Heart Failure Research Collaborative Group.

    Science.gov (United States)

    Krum, H; Shusterman, N; MacMahon, S; Sharpe, N

    1998-12-01

    The beta-blocker/vasodilator carvedilol is found to have beneficial effects in patients with chronic heart failure. However, the safety and efficacy of this agent in the presence of concomitant amiodarone therapy has not been previously determined. We retrospectively analyzed the Australia/New Zealand Carvedilol Heart Failure Research Collaborative Group study of 415 patients with mild to moderate ischemic heart failure where amiodarone was administered as part of the treatment therapy (in 52 patients). After the open-label carvedilol run-in, patients received carvedilol (target dose 25 mg twice daily) or placebo for an average of 19 months. The main adverse events during this double-blind period were worsened heart failure, hypotension/dizziness, bradycardia/atrioventricular block, and aggravation of angina. By Chi square analysis, carvedilol and amiodarone together were not associated with a greater overall incidence of adverse effects than either drug alone. The beneficial effects of carvedilol on left ventricular ejection that were observed in the main trial were preserved in the presence of amiodarone. Carvedilol is a useful additional therapy for patients with chronic heart failure already receiving amiodarone. Carvedilol can be added to amiodarone in these patients without expectation of increased adverse effects or loss of clinical efficacy.

  4. Can the Growth/Differentiation Factor-15 Be a Surrogate Target in Chronic Heart Failure Biomarker-Guided Therapy?

    Directory of Open Access Journals (Sweden)

    Alexander E. Berezin

    2017-03-01

    Full Text Available Heart failure (HF biomarker-guided therapy is a promising method, which directs to the improvement of clinical status, attenuation of admission/readmission to the hospital and reduction in mortality rate. Many biological markers, like inflammatory cytokines, are under consideration as a surrogate target for HF treatment, while there are known biomarkers with established predictive value, such as natriuretic peptides. However, discovery of new biomarkers reflecting various underlying mechanisms of HF and appearing to be surrogate targets for biomarker-guided therapy is fairly promising. Nowadays, growth/differentiation factor 15 (GDF-15 is suggested a target biomarker for HF treatment. Although elevated level of GDF-15 is associated with HF development, progression, and prognosis, there is no represented evidence regarding the direct comparison of this biomarker with other clinical risk predictors and biomarkers. Moreover, GDF-15 might serve as a contributor to endothelial progenitor cells (EPC dysfunction by inducing EPC death/autophagy and limiting their response to angiopoetic and reparative effects. The short communication was discussed whether GDF-15 is good molecular target for HF biomarker-guided therapy.

  5. Cancer stem cells, cancer cell plasticity and radiation therapy.

    Science.gov (United States)

    Vlashi, Erina; Pajonk, Frank

    2015-04-01

    Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Present and future cell therapies for pancreatic beta cell replenishment.

    Science.gov (United States)

    Domínguez-Bendala, Juan; Ricordi, Camillo

    2012-12-21

    If only at a small scale, islet transplantation has successfully addressed what ought to be the primary endpoint of any cell therapy: the functional replenishment of damaged tissue in patients. After years of less-than-optimal approaches to immunosuppression, recent advances consistently yield long-term graft survival rates comparable to those of whole pancreas transplantation. Limited organ availability is the main hurdle that stands in the way of the widespread clinical utilization of this pioneering intervention. Progress in stem cell research over the past decade, coupled with our decades-long experience with islet transplantation, is shaping the future of cell therapies for the treatment of diabetes. Here we review the most promising avenues of research aimed at generating an inexhaustible supply of insulin-producing cells for islet regeneration, including the differentiation of pluripotent and multipotent stem cells of embryonic and adult origin along the beta cell lineage and the direct reprogramming of non-endocrine tissues into insulin-producing cells.

  7. Essential role of Cdc42 in cardiomyocyte proliferation and cell-cell adhesion during heart development.

    Science.gov (United States)

    Li, Jieli; Liu, Yang; Jin, Yixin; Wang, Rui; Wang, Jian; Lu, Sarah; VanBuren, Vincent; Dostal, David E; Zhang, Shenyuan L; Peng, Xu

    2017-01-15

    Cdc42 is a member of the Rho GTPase family and functions as a molecular switch in regulating cell migration, proliferation, differentiation and survival. However, the role of Cdc42 in heart development remains largely unknown. To determine the function of Cdc42 in heart formation, we have generated a Cdc42 cardiomyocyte knockout (CCKO) mouse line by crossing Cdc42 flox mice with myosin light chain (MLC) 2a-Cre mice. The inactivation of Cdc42 in embryonic cardiomyocytes induced lethality after embryonic day 12.5. Histological analysis of CCKO embryos showed cardiac developmental defects that included thin ventricular walls and ventricular septum defects. Microarray and real-time PCR data also revealed that the expression level of p21 was significantly increased and cyclin B1 was dramatically decreased, suggesting that Cdc42 is required for cardiomyocyte proliferation. Phosphorylated Histone H3 staining confirmed that the inactivation of Cdc42 inhibited cardiomyocytes proliferation. In addition, transmission electron microscope studies showed disorganized sarcomere structure and disruption of cell-cell contact among cardiomyocytes in CCKO hearts. Accordingly, we found that the distribution of N-cadherin/β-Catenin in CCKO cardiomyocytes was impaired. Taken together, our data indicate that Cdc42 is essential for cardiomyocyte proliferation, sarcomere organization and cell-cell adhesion during heart development. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Aortic Counterpulsation Therapy in Patients with Advanced Heart Failure: Analysis of the TBRIDGE Registry

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    Cristiano Guedes Bezerra

    2016-01-01

    Full Text Available Abstract Background: The use of aortic counterpulsation therapy in advanced heart failure is controversial. Objectives: To evaluate the hemodynamic and metabolic effects of intra-aortic balloon pump (IABP and its impact on 30-day mortality in patients with heart failure. Methods: Historical prospective, unicentric study to evaluate all patients treated with IABP betwen August/2008 and July/2013, included in an institutional registry named TBRIDGE (The Brazilian Registry of Intra-aortic balloon pump in Decompensated heart failure - Global Evaluation. We analyzed changes in oxygen central venous saturation (ScvO2, arterial lactate, and use of vasoactive drugs at 48 hours after IABP insertion. The 30-day mortality was estimated by the Kaplan-Meier method and diferences in subgroups were evaluated by the Log-rank test. Results: A total of 223 patients (mean age 49 ± 14 years were included. Mean left ventricle ejection fraction was 24 ± 10%, and 30% of patients had Chagas disease. Compared with pre-IABP insertion, we observed an increase in ScvO2 (50.5% vs. 65.5%, p < 0.001 and use of nitroprusside (33.6% vs. 47.5%, p < 0.001, and a decrease in lactate levels (31.4 vs. 16.7 mg/dL, p < 0.001 and use of vasopressors (36.3% vs. 25.6%, p = 0.003 after IABP insertion. Thirty-day survival was 69%, with lower mortality in Chagas disease patients compared without the disease (p = 0.008. Conclusion: After 48 hours of use, IABP promoted changes in the use of vasoactive drugs, improved tissue perfusion. Chagas etiology was associated with lower 30-day mortality. Aortic counterpulsation therapy is an effective method of circulatory support for patients waiting for heart transplantation.

  9. Quality of life with defibrillator therapy or amiodarone in heart failure.

    Science.gov (United States)

    Mark, Daniel B; Anstrom, Kevin J; Sun, Jie L; Clapp-Channing, Nancy E; Tsiatis, Anastasios A; Davidson-Ray, Linda; Lee, Kerry L; Bardy, Gust H

    2008-09-04

    Implantable cardioverter-defibrillator (ICD) therapy significantly prolongs life in patients at increased risk for sudden death from depressed left ventricular function. However, whether this increased longevity is accompanied by deterioration in the quality of life is unclear. In a randomized trial, we compared ICD therapy or amiodarone with state-of-the-art medical therapy alone in 2521 patients who had stable heart failure with depressed left ventricular function. We prospectively measured quality of life at baseline and at months 3, 12, and 30; data collection was 93 to 98% complete. The Duke Activity Status Index (which measures cardiac physical functioning) and the Medical Outcomes Study 36-Item Short-Form Mental Health Inventory 5 (which measures psychological well-being) were prespecified primary outcomes. Multiple additional quality-of-life outcomes were also examined. Psychological well-being in the ICD group, as compared with medical therapy alone, was significantly improved at 3 months (P=0.01) and at 12 months (P=0.003) but not at 30 months. No clinically or statistically significant differences in physical functioning among the study groups were observed. Additional quality-of-life measures were improved in the ICD group at 3 months, 12 months, or both, but there was no significant difference at 30 months. ICD shocks in the month preceding a scheduled assessment were associated with a decreased quality of life in multiple domains. The use of amiodarone had no significant effects on the primary quality-of-life outcomes. In a large primary-prevention population with moderately symptomatic heart failure, single-lead ICD therapy was not associated with any detectable adverse quality-of-life effects during 30 months of follow-up. 2008 Massachusetts Medical Society

  10. The Impact of Bronchodilator Therapy on Systolic Heart Failure with Concomitant Mild to Moderate COPD

    Directory of Open Access Journals (Sweden)

    Mahoto Kato

    2017-12-01

    Full Text Available In older adults, chronic obstructive pulmonary disease (COPD is commonly associated with heart failure with reduced ejection fraction (HFrEF, and the high prevalence of this combination suggests that customized treatment is highly necessary in patients with COPD and HFrEF. To investigate whether the treatment of COPD with tiotropium, an anticholinergic bronchodilator, reduces the severity of heart failure in patients with HFrEF complicated by mild to moderate COPD, forty consecutive participants were randomly divided into two groups and enrolled in a crossover design study. Group A inhaled 18 μg tiotropium daily for 28 days and underwent observation for another 28 days. Group B completed the 28-day observation period first and then received tiotropium inhalation therapy for 28 days. Pulmonary and cardiac functions were measured on days 1, 29, and 56. In both groups, 28 days of tiotropium inhalation therapy substantially improved the left ventricular ejection fraction (from 36.3 ± 2.4% to 41.8 ± 5.9%, p < 0.01, in group A; from 35.7 ± 3.8% to 41.6 ± 3.8%, p < 0.01, in group B and plasma brain natriuretic peptide levels (from 374 ± 94 to 263 ± 92 pg/mL, p < 0.01, in group A; from 358 ± 110 to 246 ± 101 pg/mL, p < 0.01, in group B. Tiotropium inhalation therapy improves pulmonary function as well as cardiac function, and reduces the severity of heart failure in patients with compensated HFrEF with concomitant mild to moderate COPD.

  11. Intensification of Medication Therapy for Cardiorenal Syndrome in Acute Decompensated Heart Failure.

    Science.gov (United States)

    Grodin, Justin L; Stevens, Susanna R; de Las Fuentes, Lisa; Kiernan, Michael; Birati, Edo Y; Gupta, Divya; Bart, Bradley A; Felker, G Michael; Chen, Horng H; Butler, Javed; Dávila-Román, Victor G; Margulies, Kenneth B; Hernandez, Adrian F; Anstrom, Kevin J; Tang, W H Wilson

    2016-01-01

    Worsening renal function in heart failure may be related to increased venous congestion, decreased cardiac output, or both. Diuretics are universally used in acute decompensated heart failure, but they may be ineffective and may lead to azotemia. We aimed to compare the decongestive properties of a urine output-guided diuretic adjustment and standard therapy for the management of cardiorenal syndrome in acute decompensated heart failure. Data were pooled from subjects randomized to the stepwise pharmacologic care algorithm (SPCA) in the CARRESS-HF trial and those who developed cardiorenal syndrome (rise in creatinine >0.3 mg/dL) in the DOSE-AHF and ROSE-AHF trials. Patients treated with SPCA (n = 94) were compared with patients treated with standard decongestive therapy (SDT) that included intravenous loop diuretic use (DOSE-AHF and ROSE-AHF; n = 107) at the time of cardiorenal syndrome and followed for net fluid balance, weight loss, and changing renal function. The SPCA group had higher degrees of jugular venous pressure (P cardiorenal syndrome. The group that received SPCA had more weight change (-3.4 ± 5.2 lb) and more net fluid loss (1.705 ± 1.417 L) after 24 hours than the SDT group (-0.8 ± 3.4 lb and 0.892 ± 1.395 L, respectively; P < .001 for both) with a slight improvement in renal function (creatinine change -0.1 ± 0.3 vs 0.0 ± 0.3 mg/dL, respectively; P = .03). Compared with SDT, patients who received an intensification of medication therapy for treating persisting congestion had greater net fluid and weight loss without being associated with renal compromise. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Obstructive Thrombosis of Left-Sided Mechanical Heart Valves: Clinical Profile and Thrombolytic Therapy.

    Science.gov (United States)

    Chandrakasu, Arumugam; Jayachandran, Avinash; Gopinath Nayar, Pradeep; Meyyappan, Chokkalingam; Narayan, Ganesh; Basha Abdul Bari, Ahamed; Johnson Samuel, Prince

    2017-05-01

    Thrombosis of a mechanical prosthetic heart valve is a potentially life-threatening complication associated with a high mortality. Although thrombolytic therapy has been considered highly beneficial in this situation, very few studies have been conducted to monitor the effectiveness of such thrombolytic therapy among Asian populations. Hence, the study aim was to evaluate the clinical profile, efficacy and safety of the thrombolytic agent streptokinase (SK) in patients with obstructive thrombosis of a left-sided mechanical heart valve. Patients (n = 30) with left-sided mechanical heart valve thrombosis (LSMHVT) who had been managed with SK during the past four years were included in this retrospective study. Clinical features such as presenting symptoms based on NYHA functional class, prosthetic valve position, oral anticoagulant compliance, International Normalized Ratio (INR) and imaging methods including fluoroscopy, transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were evaluated. In addition, the effectiveness and complications of SK were analyzed. The majority of patients presented with advanced NYHA class (III and IV, each 40%). Obstructive thromboses were observed at the mitral prosthesis in 70% of cases, at the aortic prosthesis in 27%, and at both valves in 3%. All patients underwent TTE, but fluoroscopy was used more often than TEE. Despite compliance with oral anticoagulation therapy, a sub-therapeutic INR was observed in 40% of cases at the time of presentation. Overall, thrombolysis was successful in 80% of patients using intravenous SK, with 100% success in patients in NYHA classes I-III and 42% for NYHA class IV. Moreover, embolic complications occurred in only a small number of patients. In patients with obstructive thrombosis of LSMHVT, intravenous SK was effective and should be considered as first choice in patients in NYHA classes I-III, and as an acceptable alternative in those in NYHA class IV.

  13. Antioxidant gene therapy against neuronal cell death

    Science.gov (United States)

    Navarro-Yepes, Juliana; Zavala-Flores, Laura; Annadurai, Anandhan; Wang, Fang; Skotak, Maciej; Chandra, Namas; Li, Ming; Pappa, Aglaia; Martinez-Fong, Daniel; Razo, Luz Maria Del; Quintanilla-Vega, Betzabet; Franco, Rodrigo

    2014-01-01

    Oxidative stress is a common hallmark of neuronal cell death associated with neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, as well as brain stroke/ischemia and traumatic brain injury. Increased accumulation of reactive species of both oxygen (ROS) and nitrogen (RNS) has been implicated in mitochondrial dysfunction, energy impairment, alterations in metal homeostasis and accumulation of aggregated proteins observed in neurodegenerative disorders, which lead to the activation/modulation of cell death mechanisms that include apoptotic, necrotic and autophagic pathways. Thus, the design of novel antioxidant strategies to selectively target oxidative stress and redox imbalance might represent important therapeutic approaches against neurological disorders. This work reviews the evidence demonstrating the ability of genetically encoded antioxidant systems to selectively counteract neuronal cell loss in neurodegenerative diseases and ischemic brain damage. Because gene therapy approaches to treat inherited and acquired disorders offer many unique advantages over conventional therapeutic approaches, we discussed basic research/clinical evidence and the potential of virus-mediated gene delivery techniques for antioxidant gene therapy. PMID:24333264

  14. Cost-effectiveness of defibrillator therapy or amiodarone in chronic stable heart failure: results from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT).

    Science.gov (United States)

    Mark, Daniel B; Nelson, Charlotte L; Anstrom, Kevin J; Al-Khatib, Sana M; Tsiatis, Anastasios A; Cowper, Patricia A; Clapp-Channing, Nancy E; Davidson-Ray, Linda; Poole, Jeanne E; Johnson, George; Anderson, Jill; Lee, Kerry L; Bardy, Gust H

    2006-07-11

    In the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), implantable cardioverter-defibrillator (ICD) therapy significantly reduced all-cause mortality rates compared with medical therapy alone in patients with stable, moderately symptomatic heart failure, whereas amiodarone had no benefit on mortality rates. We examined long-term economic implications of these results. Medical costs were estimated by using hospital billing data and the Medicare Fee Schedule. Our base case cost-effectiveness analysis used empirical clinical and cost data to estimate the lifetime incremental cost of saving an extra life-year with ICD therapy relative to medical therapy alone. At 5 years, the amiodarone arm had a survival rate equivalent to that of the placebo arm and higher costs than the placebo arm. For ICD relative to medical therapy alone, the base case lifetime cost-effectiveness and cost-utility ratios (discounted at 3%) were dollar 38,389 per life-year saved (LYS) and dollar 41,530 per quality-adjusted LYS, respectively. A cost-effectiveness ratio < dollar 100,000 was obtained in 99% of 1000 bootstrap repetitions. The cost-effectiveness ratio was sensitive to the amount of extrapolation beyond the empirical 5-year trial data: dollar 127,503 per LYS at 5 years, dollar 88,657 per LYS at 8 years, and dollar 58,510 per LYS at 12 years. Because of a significant interaction between ICD treatment and New York Heart Association class, the cost-effectiveness ratio was dollar 29,872 per LYS for class II, whereas there was incremental cost but no incremental benefit in class III. Prophylactic use of single-lead, shock-only ICD therapy is economically attractive in patients with stable, moderately symptomatic heart failure with an ejection fraction < or = 35%, particularly those in NYHA class II, as long as the benefits of ICD therapy observed in the SCD-HeFT persist for at least 8 years.

  15. Cellular modifications and interventions for the damaged heart

    NARCIS (Netherlands)

    Engels, M.C.

    2016-01-01

    The aim of this thesis was to explore cellular modification processes associated with heart disease, as well as harnessing its potential for treatment and prevention of detrimental electrophysiological consequences of heart disease. For regenerative cell replacement therapies, optimal

  16. Optimal Cardiac Resynchronization Therapy Pacing Rate in Non-Ischemic Heart Failure Patients

    DEFF Research Database (Denmark)

    Ghotbi, Adam Ali; Sander, Mikael; Køber, Lars

    2015-01-01

    BACKGROUND: The optimal pacing rate during cardiac resynchronization therapy (CRT) is unknown. Therefore, we investigated the impact of changing basal pacing frequencies on autonomic nerve function, cardiopulmonary exercise capacity and self-perceived quality of life (QoL). METHODS: Twelve CRT...... by microneurography (MSNA), peak oxygen consumption (pVO2), N-terminal pro-brain natriuretic peptide (p-NT-proBNP), echocardiography and QoL. RESULTS: DDD-80 pacing for 3 months increased the mean heart rate from 77.3 to 86.1 (p = 0.001) and reduced sympathetic activity compared to DDD-60 (51±14 bursts/100 cardiac...

  17. Distinct trajectories of disease-specific health status in heart failure patients undergoing cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Mastenbroek, Mirjam H.; Pedersen, Susanne S.; Meine, Mathias

    2016-01-01

    PURPOSE: It is well known that a significant proportion of heart failure patients (10-44 %) do not show improvement in symptoms or functioning from cardiac resynchronization therapy (CRT), yet no study has examined patient-reported health status trajectories after implantation. METHODS: A cohort......-specific health status over time. RESULTS: All health status trajectories showed an initial small to large improvement from baseline to 2-month follow-up, whereafter most trajectories displayed a stable pattern between short- and long-term follow-up. Low educational level, NYHA class III/IV, smoking, no use...

  18. Combination therapy with beta-adrenergic receptor antagonists and phosphodiesterase inhibitors for chronic heart failure.

    Science.gov (United States)

    Van Tassell, Benjamin W; Radwanski, Przemyslaw; Movsesian, Matthew; Munger, Mark A

    2008-12-01

    Abstract Rational use of phosphodiesterase inhibitors represents an ongoing controversy in contemporary pharmacotherapy for heart failure. In randomized clinical trials, phosphodiesterase inhibitors increased cardiac output at the expense of worsening the rates of sudden cardiac death and cardiovascular mortality. Preliminary findings from ongoing clinical and preclinical investigations of phosphodiesterase activity suggest that combined use of phosphodiesterase inhibitors with beta-adrenergic antagonists may prevent these adverse outcomes. Compartmentation of cyclic adenosine 3',5'-monophosphate signaling may prove critical in determining myocardial response to combination therapy.

  19. Meta-analysis of combined therapy with angiotensin receptor antagonists versus ACE inhibitors alone in patients with heart failure.

    Directory of Open Access Journals (Sweden)

    Andrea Kuenzli

    Full Text Available BACKGROUND: There is insufficient evidence whether the benefit of adding angiotensin II receptor blockers (ARBs to angiotensin-converting enzyme (ACE inhibitors outweighs the increased risk of adverse effects in patients with heart failure. METHODOLOGY/PRINCIPAL FINDINGS: Two independent reviewers searched and abstracted randomized controlled trials of ARBs and ACE inhibitors compared to ACE inhibitor therapy alone in patients with heart failure reporting mortality and hospitalizations having a follow-up of at least 6 months identified by a systematic literature search. Eight trials including a total of 18,061 patients fulfilled our inclusion criteria. There was no difference between patients treated with combination therapy and ACE inhibitor therapy alone for overall mortality, hospitalization for any reason, fatal or nonfatal MI. Combination therapy was, however, associated with fewer hospital admissions for heart failure (RR 0.81, 95%CI 0.72-0.91, although there was significant heterogeneity across trials (p-value for heterogeneity = 0.04; I(2 = 57% [95%CI 0-83%]. Patients treated with combination therapy had a higher risk of worsening renal function and symptomatic hypotension, and their trial medications were more often permanently discontinued. Lack of individual patient data precluded the analysis of time-to-event data and identification of subgroups which potentially benefit more from combination therapy such as younger patients with preserved renal function and thus at lower risk to experience worsening renal function or hyperkalemia. CONCLUSIONS/SIGNIFICANCE: Combination therapy with ARBs and ACE inhibitors reduces admissions for heart failure in patients with congestive heart failure when compared to ACE inhibitor therapy alone, but does not reduce overall mortality or all-cause hospitalization and is associated with more adverse events. Thus, based on current evidence, combination therapy with ARBs and ACE inhibitors may be reserved

  20. Mesenchymal Stromal Cell Therapy in Crohn's Disease.

    Science.gov (United States)

    Forbes, Geoffrey M

    2017-01-01

    Mesenchymal stromal cells (MSC) are multipotent adult stem cells with immunomodulatory properties. They uniquely express HLA class I antigen at a low level, and do not express HLA class II. Hence, for allogeneic administration, donor to recipient matching is not required; yet a prolonged chimeric state does not occur. Contrary to haematopoietic stem cell transplantation, cytotoxic drug therapy is not required to harvest, or administer, cells. Key Messages: MSC are obtained from marrow, adipose tissue or placenta. In our centre, MSC are isolated from a 10 ml donor marrow aspirate, by virtue of their adherence to plastic. They are expanded in culture, cryopreserved, and subjected to strict quality controls before release for intravenous administration. These activities occur in a dedicated, nationally accredited, laboratory. Initial observations of allogeneic MSC efficacy were in graft-versus-host disease. Both autologous and allogeneic MSC have since been evaluated in biologic refractory luminal and fistulising Crohn's disease (CD). Data from early-phase studies have suggested efficacy for luminal disease when allogeneic MSC were given intravenously and also suggested efficacy for fistulising disease when either allogeneic or autologous MSC were administered into fistulas. MSC treatment is not reported to have caused serious adverse events. Although in vitro criteria for defining MSC exist, a major challenge lies in how to define MSC for clinical use. MSC function in vivo is likely to be dependent upon donor immunological characteristics, and widely varying manufacturing processes between laboratories. MSC dose, frequency of administration, stage of disease, and presence of concomitant immunosuppression also require to be defined. MSC therapy may have future utility in CD, but considerable work is first required to determine appropriate phenotypic and functional characteristics of administered cells. © 2017 S. Karger AG, Basel.

  1. Primary stroke in a woman with sickle cell anemia responsive to hydroxyurea therapy.

    Science.gov (United States)

    Ballas, Samir K; Martinez, Ubaldo; Savage, Michael

    2014-01-01

    The most common cause of stroke in children with sickle cell anemia is infarction due to ischemia. In adults, however, stroke is most commonly hemorrhagic in nature. Other causes of stroke in patients with sickle cell disease are very rare. In this short communication, we describe a woman with sickle cell anemia responsive to hydroxyurea (HU) therapy who had primary stroke due to paradoxical embolization caused by a large atrial septal defect. Successful management of the stroke included surgical closure of the defect with trans-esophageal echocardiographic guidance. To the best of our knowledge, this is the first patient with sickle cell anemia and stroke due to congenital heart disease who did not require open heart surgery for successful management.

  2. Cell-Based Therapy for Silicosis

    Directory of Open Access Journals (Sweden)

    Miquéias Lopes-Pacheco

    2016-01-01

    Full Text Available Silicosis is the most common pneumoconiosis globally, with higher prevalence and incidence in developing countries. To date, there is no effective treatment to halt or reverse the disease progression caused by silica-induced lung injury. Significant advances have to be made in order to reduce morbidity and mortality related to silicosis. In this review, we have highlighted the main mechanisms of action that cause lung damage by silica particles and summarized the data concerning the therapeutic promise of cell-based therapy for silicosis.

  3. Cell-Based Therapy for Silicosis

    Science.gov (United States)

    Lopes-Pacheco, Miquéias; Bandeira, Elga; Morales, Marcelo M.

    2016-01-01

    Silicosis is the most common pneumoconiosis globally, with higher prevalence and incidence in developing countries. To date, there is no effective treatment to halt or reverse the disease progression caused by silica-induced lung injury. Significant advances have to be made in order to reduce morbidity and mortality related to silicosis. In this review, we have highlighted the main mechanisms of action that cause lung damage by silica particles and summarized the data concerning the therapeutic promise of cell-based therapy for silicosis. PMID:27066079

  4. [Retinal Cell Therapy Using iPS Cells].

    Science.gov (United States)

    Takahashi, Masayo

    2016-03-01

    Progress in basic research, starting with the work on neural stem cells in the middle 1990's to embryonic stem (ES) cells and induced pluripotent stem (iPS) cells at present, will lead the cell therapy (regenerative medicine) of various organs, including the central nervous system to a big medical field in the future. The author's group transplanted iPS cell-derived retinal pigment epithelial (RPE) cell sheets to the eye of a patient with exudative age-related macular degeneration (AMD) in 2014 as a clinical research. Replacement of the RPE with the patient's own iPS cell-derived young healthy cell sheet will be one new radical treatment of AMD that is caused by cellular senescence of RPE cells. Since it was the first clinical study using iPS cell-derived cells, the primary endpoint was safety judged by the outcome one year after surgery. The safety of the cell sheet has been confirmed by repeated tumorigenisity tests using immunodeficient mice, as well as purity of the cells, karyotype and genetic analysis. It is, however, also necessary to prove the safety by clinical studies. Following this start, a good strategy considering cost and benefit is needed to make regenerative medicine a standard treatment in the future. Scientifically, the best choice is the autologous RPE cell sheet, but autologous cell are expensive and sheet transplantation involves a risky part of surgical procedure. We should consider human leukocyte antigen (HLA) matched allogeneic transplantation using the HLA 6 loci homozyous iPS cell stock that Prof. Yamanaka of Kyoto University is working on. As the required forms of donor cells will be different depending on types and stages of the target diseases, regenerative medicine will be accomplished in a totally different manner from the present small molecule drugs. Proof of concept (POC) of photoreceptor transplantation in mouse is close to being accomplished using iPS cell-derived photoreceptor cells. The shortest possible course for treatment

  5. Cellular Therapeutics for Heart Failure: Focus on Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Amitabh C. Pandey

    2017-01-01

    Full Text Available Resulting from a various etiologies, the most notable remains ischemia; heart failure (HF manifests as the common end pathway of many cardiovascular processes and remains among the top causes for hospitalization and a major cause of morbidity and mortality worldwide. Current pharmacologic treatment for HF utilizes pharmacologic agents to control symptoms and slow further deterioration; however, on a cellular level, in a patient with progressive disease, fibrosis and cardiac remodeling can continue leading to end-stage heart failure. Cellular therapeutics have risen as the new hope for an improvement in the treatment of HF. Mesenchymal stem cells (MSCs have gained popularity given their propensity of promoting endogenous cellular repair of a myriad of disease processes via paracrine signaling through expression of various cytokines, chemokines, and adhesion molecules resulting in activation of signal transduction pathways. While the exact mechanism remains to be completely elucidated, this remains the primary mechanism identified to date. Recently, MSCs have been incorporated as the central focus in clinical trials investigating the role how MSCs can play in the treatment of HF. In this review, we focus on the characteristics of MSCs that give them a distinct edge as cellular therapeutics and present results of clinical trials investigating MSCs in the setting of ischemic HF.

  6. Oncolytic vaccinia therapy of squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Yu Yong A

    2009-07-01

    Full Text Available Abstract Background Novel therapies are necessary to improve outcomes for patients with squamous cell carcinomas (SCC of the head and neck. Historically, vaccinia virus was administered widely to humans as a vaccine and led to the eradication of smallpox. We examined the therapeutic effects of an attenuated, replication-competent vaccinia virus (GLV-1h68 as an oncolytic agent against a panel of six human head and neck SCC cell lines. Results All six cell lines supported viral transgene expression (β-galactosidase, green fluorescent protein, and luciferase as early as 6 hours after viral exposure. Efficient transgene expression and viral replication (>150-fold titer increase over 72 hrs were observed in four of the cell lines. At a multiplicity of infection (MOI of 1, GLV-1h68 was highly cytotoxic to the four cell lines, resulting in ≥ 90% cytotoxicity over 6 days, and the remaining two cell lines exhibited >45% cytotoxicity. Even at a very low MOI of 0.01, three cell lines still demonstrated >60% cell death over 6 days. A single injection of GLV-1h68 (5 × 106 pfu intratumorally into MSKQLL2 xenografts in mice exhibited localized intratumoral luciferase activity peaking at days 2–4, with gradual resolution over 10 days and no evidence of spread to normal organs. Treated animals exhibited near-complete tumor regression over a 24-day period without any observed toxicity, while control animals demonstrated rapid tumor progression. Conclusion These results demonstrate significant oncolytic efficacy by an attenuated vaccinia virus for infecting and lysing head and neck SCC both in vitro and in vivo, and support its continued investigation in future clinical trials.

  7. Genetic Engineering of Mesenchymal Stem Cells and Its Application in Human Disease Therapy

    Science.gov (United States)

    Hodgkinson, Conrad P.; Gomez, José A.; Mirotsou, Maria

    2010-01-01

    Abstract The use of stem cells for tissue regeneration and repair is advancing both at the bench and bedside. Stem cells isolated from bone marrow are currently being tested for their therapeutic potential in a variety of clinical conditions including cardiovascular injury, kidney failure, cancer, and neurological and bone disorders. Despite the advantages, stem cell therapy is still limited by low survival, engraftment, and homing to damage area as well as inefficiencies in differentiating into fully functional tissues. Genetic engineering of mesenchymal stem cells is being explored as a means to circumvent some of these problems. This review presents the current understanding of the use of genetically engineered mesenchymal stem cells in human disease therapy with emphasis on genetic modifications aimed to improve survival, homing, angiogenesis, and heart function after myocardial infarction. Advancements in other disease areas are also discussed. PMID:20825283

  8. Beneficial effects of adaptive servo-ventilation therapy on albuminuria in patients with heart failure.

    Science.gov (United States)

    Tamura, Yoshikazu; Koyama, Takashi; Watanabe, Hiroyuki; Hosoya, Tomoki; Ito, Hiroshi

    2015-05-01

    Short-duration adaptive servo-ventilation (ASV) therapy can be effective for heart failure (HF) patients. Albuminuria is recognized as a prognostic marker for HF. We investigated whether short-duration and short-term ASV therapy reduced albuminuria in HF patients. Twenty-one consecutive HF patients were divided into two groups: those who tolerated ASV therapy (ASV group, n=14) and those who did not (non-ASV group, n=7). ASV therapy was administered to enrolled patients for 1 week for 2h per day (1h in the morning and 1h in the afternoon). The urinary albumin to creatinine ratio (UACR), urinary 24h norepinephrine (NE) excretion, high-sensitivity C-reactive protein (hs-CRP), and plasma brain natriuretic peptide (BNP) levels were measured before and 1 week after ASV therapy. In the ASV group, but not the non-ASV group, the UACR significantly decreased, together with a decrease in urinary NE and hs-CRP levels. There were significant correlations between the changes in UACR and hs-CRP and between the changes in urinary NE and hs-CRP. Multiple linear regression analyses indicated that ASV use was the strongest predictor of decreased UACR. Albuminuria, urinary NE, and hs-CRP levels reduced in HF patients who could receive short-duration and short-term ASV therapy. Anti-inflammatory effects of ASV therapy may partly mediate the reduction of albuminuria. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  9. [Testosterone therapy improves cardiac function of male rats with right heart failure].

    Science.gov (United States)

    Li, Zong-Bin; Wang, Jing; Wang, Ju-Xiang; Chen, Xun-Min; Jiang, Shi-Sen

    2009-11-01

    Clinical studies have shown decreased levels of sexual hormones, particularly testosterone deficiency, in men with chronic heart failure (CHF). The authors aimed to investigate the effect of testosterone on cardiac function and the possible mechanism of androgen protecting the heart in male rats. Forty-three male SD rats were randomly divided into 3 groups: right heart failure (RHF, n = 15), physiologic testosterone treatment (TT, n = 15) and control (n = 13). The RHF group was given intraperitoneal injection of monocrotaline at 60 mg/kg to make RHF models; the TT group was injected with testosterone at 5 mg/kg 3 days after monocrotaline administration; and the control group received equal volume of saline. The CD34+ cells in the peripheral blood of each rat were counted by flow cytometry. The levels of serum testosterone and tumor necrosis factor alpha (TNF-alpha) were measured by chemiluminescence immunoassay and enzyme linked immunosorbent assay, respectively. The hearts, lungs and livers of all the surviving rats were excised at 6 weeks for pathological and immunohistochemical examinations. The level of serum testosterone was gradually decreased, while that of TNF-alpha obviously increased in the RHF group. After testosterone treatment, the TT group showed a remarkable improvement of cardiac performance and a significant decrease in the level of serum TNF-alpha as compared with the RHF group. Statistically significant differences were observed neither in the CD34+ cell count in the peripheral blood nor in the CD34+ expression of the myocardial cells between the TT and RHF groups. Physiological supplementation of testosterone can improve the cardiac function of RHF male rats, probably through its inhibition of TNF-alpha rather than by autologous mobilization of bone marrow stem cells.

  10. Effectiveness of behavioral-cognitive group therapy on depression, anxiety, and stress of patients with coronary heart disease.

    Science.gov (United States)

    Aghaei, M; Samkhaniyan, E; Mahdavi, A; Faraji, J; Roshandel, Z

    2015-01-01

    Objective. An appropriate psychological intervention to promote the level of mental health of patients with a coronary heart has a great importance. The existing investigation aimed to study the effectiveness of the behavioral-cognitive group therapy on depression, anxiety, and stress of patients with coronary heart disease. Methodology. The current study was quasi-experimental with a pretest-posttest that used a control group. Hence, 30 of the patients with coronary heart disease in Shahid Rajaee heart center in Tehran chose to use the convenience sampling method and were put in an experimental group and a control group. Both groups were pretested by using a demographic questionnaire, and scale of depression, anxiety, and stress DASS-42. Afterwards, the experimental group was trained for eight sessions of cognitive-behavioral club therapy and the control society gained no intervention. Later, both groups were post-tested, and the acquired information were analyzed by using inferential and descriptive statistical methods accompanied by SPSS 21 software. Findings. The results indicated that the cognitive-behavioral group therapy training significantly reduced depression, anxiety, and stress in patients with coronary heart disease. Conclusion. What should be understood from this study is that the cognitive-behavioral group therapy training had a great positive impact on the decrease of depression, anxiety, and tension in patients with coronary heart disease, since it had an economic cost and a great acceptability by the cases, especially when it was performed in a group.

  11. [Vismodegib Therapy for Periocular Basal Cell Carcinoma].

    Science.gov (United States)

    Keserü, M; Green, S; Dulz, S

    2017-01-01

    Background Basal cell carcinoma (BCC) is the commonest periorbital tumour. Mohs' micrographic surgery and secondary reconstruction is the therapeutic gold standard for periorbital BCC. In cases of inoperability for any reason, therapeutic alternatives are needed. Since the approval of vismodegib, an orally administered, targeted BCC therapy is available. Nevertheless there is little information on the use of vismodegib for periorbital BCC. Patients and Methods In a retrospective study, we analysed the data of 4 patients treated with vismodegib since 2014. The patients' mean age before starting therapy was 87 years. The mean maximum tumour diameter was 22.0 mm. Results The median follow-up was 17 months. The median treatment duration was 7.5 months. In 75 % of patients, complete clinical remission of BCC was achieved. In 25 % of patients, interim stabilisation of tumour growth was possible. The most common side effect of therapy was muscle spasm. Conclusion Vismodegib is an effective treatment option for patients with periorbital BCC, in whom surgical treatment is not possible for any reason. Georg Thieme Verlag KG Stuttgart · New York.

  12. Mesenchymal stem cells for regenerative therapy: optimization of cell preparation protocols.

    Science.gov (United States)

    Ikebe, Chiho; Suzuki, Ken

    2014-01-01

    Administration of bone marrow-derived mesenchymal stem cells (MSCs) is an innovative approach for the treatment of a range of diseases that are not curable by current therapies including heart failure. A number of clinical trials have been completed and many others are ongoing; more than 2,000 patients worldwide have been administered with culture-expanded allogeneic or autologous MSCs for the treatment of various diseases, showing feasibility and safety (and some efficacy) of this approach. However, protocols for isolation and expansion of donor MSCs vary widely between these trials, which could affect the efficacy of the therapy. It is therefore important to develop international standards of MSC production, which should be evidence-based, regulatory authority-compliant, of good medical practice grade, cost-effective, and clinically practical, so that this innovative approach becomes an established widely adopted treatment. This review article summarizes protocols to isolate and expand bone marrow-derived MSCs in 47 recent clinical trials of MSC-based therapy, which were published after 2007 onwards and provided sufficient methodological information. Identified issues and possible solutions associated with the MSC production methods, including materials and protocols for isolation and expansion, are discussed with reference to relevant experimental evidence with aim of future clinical success of MSC-based therapy.

  13. Effect of Induction Therapy on Graft Survival in Primary Pediatric Heart Transplantation: A Propensity Score Analysis of the UNOS Database.

    Science.gov (United States)

    Butts, Ryan; Davis, Melanie; Savage, Andrew; Burnette, Ali; Kavarana, Minoo; Bradley, Scott; Atz, Andrew; Nietert, Paul J

    2017-06-01

    The use of induction therapy in pediatric heart transplantation has increased. The aim of this study was to investigate the effects of induction therapy on graft survival. The United Network for Organ Sharing database was queried for isolated pediatric heart transplants from January 1, 1994, to December 31, 2013. Propensity scores for induction treatment were calculated by estimating probability of induction using a logistic regression model. Transplants were then matched between induction treatment groups based on the propensity score, reducing potential biases. Using only propensity score matched transplants, the effect of induction therapy on graft survival was investigated using Cox-proportional hazards. Subgroup analyses were performed based on age, race, recipient cardiac diagnosis, HLA, and recipient panel-reactive antibody (PRA). Of 4565 pediatric primary heart transplants from 1994 to 2013, 3741 had complete data for the propensity score calculation. There were 2792 transplants successfully matched (induction, n = 1396; no induction, n = 1396). There were no significant differences in transplant and pretransplant covariates between induction and no induction groups. In the Cox-proportional hazards model, the use of induction of was not associated with graft loss (hazard ratio [HR], 0.88; 95% confidence interval [95% CI], 0.75-1.01; P = 0.07). In subgroup analyses, induction therapy may be associated with improved survival in patients with PRA greater than 50% (HR, 0.57; 95% CI, 0.34-0.97) and congenital heart disease (HR, 0.78; 95% CI, 0.64-0.96). Induction therapy is not associated with improved graft survival in primary pediatric heart transplantation. However, in pediatric heart transplant recipients with PRA greater than 50% or congenital heart disease, induction therapy is associated with improved survival.

  14. Iron therapy in heart failure patients without anaemia: possible implications for chronic kidney disease patients.

    Science.gov (United States)

    Malyszko, Jolanta; Anker, Stefan D

    2017-12-01

    Iron deficiency anaemia is a global health problem that manifests as fatigue and poor physical endurance. Anaemia can be caused by dietary iron deficiency, blood loss or a combination of poor iron absorption and ineffective iron mobilization in patients with chronic disease. Nephrologists caring for patients with impaired renal function understand that iron treatment is necessary to provide adequate iron for erythropoiesis during the treatment of overt anaemia. However, a less well-understood health problem is iron deficiency, which creates symptoms that overlap with those of anaemia and often occurs in concert with chronic disease. Recently, several randomized controlled clinical trials have been conducted to investigate the effects of treatment with intravenous iron in heart failure patients with iron deficiency who may or may not also have anaemia. Given that heart and kidney disease are often comorbid, these clinical trials may have implications for the way nephrologists view their patients with iron deficiency. In this article, we review several clinical studies of intravenous iron therapy for patients with iron deficiency and heart failure and discuss possible implications for the treatment of patients with kidney disease.

  15. The evolution and benefit of device therapy in patients listed for heart transplant.

    Science.gov (United States)

    Vandenberk, Bert; Hinderks, Mark; Voros, Gabor; Garweg, Christophe; Vanhaecke, Johan; Willems, Rik

    2017-03-09

    The latest 2015 ESC Guidelines on the prevention of sudden cardiac death make a Class IIa recommendation for ICD implantation in patients listed for heart transplantation. This recommendation was based on expert consensus in view of the sparsity of data. All patients listed for heart transplantation at the University Hospitals of Leuven from 2002 until 2014 were studied retrospectively. Exclusion criteria were age HR 4.38, 95%CI 2.11-9.01), a history of stroke (HR 2.95, 95%CI 1.61-5.40), older age (HR 1.03, 95%CI 1.01-1.05) and a worse renal function (HR 1.15, 95%CI 1.00-1.33). The time on the waiting list for heart transplantation significantly increased together with an increased use of device therapy in this population. The proportion of patients reaching transplant remained unchanged. This patient group is prone to life-threatening arrhythmias and the use of an ICD may improve survival.

  16. Novel markers and therapies for patients with acute heart failure and renal dysfunction.

    Science.gov (United States)

    McCullough, Peter A; Jefferies, John L

    2015-03-01

    Acute kidney injury complicates decompensated heart failure in ∼33% of cases and is associated with morbidity and mortality; thus, we sought to systematically review this topic in order to summarize novel diagnostic and therapeutic approaches. Structured PubMed searches on these topics were conducted in February 2014 and relevant literature was identified. The PubMed search identified a total of 192 articles that were individually screened for inclusion in this analysis, and 58 were included. Acute kidney injury, defined by substantial increases in serum creatinine, is associated consistently with prolonged length of stay, rehospitalization, and mortality. Biomarker studies suggested that natriuretic peptides are prognostic for shorter- and longer-term mortality. Novel proteins indicating kidney damage and albumin in the urine are associated with acute kidney injury. The most promising acute pharmacologic treatment appears to be serelaxin, which has been shown to improve acute heart failure symptoms, hemodynamic parameters, and renal function. The presence of acute kidney injury results in worse clinical outcomes for patients with acute heart failure. Novel biomarkers and therapies hold the promise of improving both cardiac and renal outcomes in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Neurohumoral Modulation During Waon Therapy in Chronic Heart Failure - Subanalysis of Waon-CHF Study.

    Science.gov (United States)

    Ichiki, Tomoko; Burnett, John C; Scott, Christopher G; Heublein, Denise M; Miyata, Masaaki; Kinugawa, Koichiro; Inoue, Teruo; Tei, Chuwa

    2017-04-25

    Heart failure (HF) is a disease of neurohumoral dysfunction and current pharmacological therapies for HF have not improved mortality rates, thus requiring additional new strategies. Waon therapy for HF patients may be a complementary strategy with peripheral vasodilation via nitric oxide. We hypothesized that Waon therapy would improve neurohumoral factors, such as natriuretic peptides (NP) and the renin-angiotensin-aldosterone system (RAAS) in HF.Methods and Results:Plasma samples were collected from patients enrolled in the WAON-CHF Study (Waon therapy (n=77) or control (n=73)) before and after the treatment. B-type NP (BNP), C-type NP (CNP), and aldosterone (Aldo) levels were measured by respective specific radioimmunoassays. Although clinical parameters significantly improved in the Waon group compared with the control group, BNP, Aldo, and CNP levels were not statistically different between groups. On subanalysis with patient variables, BNP levels were improved in the Waon group treated with angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker or spironolactone. In addition, Aldo levels were improved in the Waon group patients with diabetes mellitus, hypertension, and inotrope use, and CNP levels were improved in Waon group patients with estimated glomerular filtration rate CHF Study: UMIN000006705).

  18. Epicardial shock-wave therapy improves ventricular function in a porcine model of ischaemic heart disease.

    Science.gov (United States)

    Holfeld, Johannes; Zimpfer, Daniel; Albrecht-Schgoer, Karin; Stojadinovic, Alexander; Paulus, Patrick; Dumfarth, Julia; Thomas, Anita; Lobenwein, Daniela; Tepeköylü, Can; Rosenhek, Raphael; Schaden, Wolfgang; Kirchmair, Rudolf; Aharinejad, Seyedhossein; Grimm, Michael

    2016-12-01

    Previously we have shown that epicardial shock-wave therapy improves left ventricular ejection fraction (LVEF) in a rat model of myocardial infarction. In the present experiments we aimed to address the safety and efficacy of epicardial shock-wave therapy in a preclinical large animal model and to further evaluate mechanisms of action of this novel therapy. Four weeks after left anterior descending (LAD) artery ligation in pigs, the animals underwent re-thoracotomy with (shock-wave group, n = 6) or without (control group, n = 5) epicardial shock waves (300 impulses at 0.38 mJ/mm2 ) applied to the infarcted anterior wall. Efficacy endpoints were improvement of LVEF and induction of angiogenesis 6 weeks after shock-wave therapy. Safety endpoints were haemodynamic stability during treatment and myocardial damage. Four weeks after LAD ligation, LVEF decreased in both the shock-wave (43 ± 3%, p heart failure exerted a positive effect on LVEF improvement and did not show any adverse effects. Angiogenesis was induced by stimulation of VEGF receptors. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

  19. Lung capillary injury and repair in left heart disease: a new target for therapy?

    Science.gov (United States)

    Azarbar, Sayena; Dupuis, Jocelyn

    2014-07-01

    The lungs are the primary organs affected in LHD (left heart disease). Increased left atrial pressure leads to pulmonary alveolar-capillary stress failure, resulting in cycles of alveolar wall injury and repair. The reparative process causes the proliferation of MYFs (myofibroblasts) with fibrosis and extracellular matrix deposition, resulting in thickening of the alveolar wall. Although the resultant reduction in vascular permeability is initially protective against pulmonary oedema, the process becomes maladaptive causing a restrictive lung syndrome with impaired gas exchange. This pathological process may also contribute to PH (pulmonary hypertension) due to LHD. Few clinical trials have specifically evaluated lung structural remodelling and the effect of related therapies in LHD. Currently approved treatment for chronic HF (heart failure) may have direct beneficial effects on lung structural remodelling. In the future, novel therapies specifically targeting the remodelling processes may potentially be utilized. In the present review, we summarize data supporting the clinical importance and pathophysiological mechanisms of lung structural remodelling in LHD and propose that this pathophysiological process should be explored further in pre-clinical studies and future therapeutic trials.

  20. Results of a non-specific immunomodulation therapy on chronic heart failure (ACCLAIM trial): a placebo-controlled randomised trial

    DEFF Research Database (Denmark)

    Torre-Amione, G.; Anker, S.D.; Bourge, R.C.

    2008-01-01

    -controlled study of a device-based non-specific immunomodulation therapy (IMT) in patients with New York Heart Association (NYHA) functional class II-IV chronic heart failure, left ventricular (LV) systolic dysfunction, and hospitalisation for heart failure or intravenous drug therapy in an outpatient setting...... within the past 12 months. Patients were randomly assigned to receive IMT (n=1213) or placebo (n=1213) by intragluteal injection on days 1, 2, 14, and every 28 days thereafter. Primary endpoint was the composite of time to death from any cause or first hospitalisation for cardiovascular reasons...... events in the IMT group and 429 in the placebo group (hazard ratio 0 . 92; 95% CI 0 . 80-1.05; p=0 . 22). In two prespecified subgroups of patients-those with no history of previous myocardial infarction (n=919) and those with NYHA II heart failure (n=689)-IMT was associated with a 26% (0.74; 0 . 57...

  1. Gene and Stem Cell Therapy: Alone or in Combination?

    Directory of Open Access Journals (Sweden)

    Mohammad A. Rafi

    2011-12-01

    Full Text Available Introduction: Both gene and stem cell therapies hold great promise in the treatment of many genetic diseases and are currently focus of interest for many investigators. While both approaches are offering great and valuable treatment options for devastating and life-threatening diseases, they hold much greater promise in combination. Methods: As there are multiple options in selecting gene transfer vehicles among the non-viral and viral vectors, there are also many options among the different transplantable cell types ranging from lineage-restricted progenitor cells to multipotent and pluripotent stem cells. Here, combination of the gene therapy and stem cell therapy is discussed. Results: Several successful gene and stem cell therapies have been reported both in animal and human trials. Combination of the gene therapy and stem cell therapy can be carried out sequentially where the cell transplantation and the in vivo gene therapy are accomplished one after the other; or, as it is more commonly practiced, they can be carried out as ex vivo gene therapy where the transplantable cells are genetically modified outside the body before being transplanted into the body. Conclusion: The combination of the stem-cell technology with gene therapy has the potential of providing both regenerative tissue and therapeutic material simultaneously; therefore, having the benefits of both technologies.

  2. Region and cell-type resolved quantitative proteomic map of the human heart

    DEFF Research Database (Denmark)

    Doll, Sophia; Dreßen, Martina; Geyer, Philipp E

    2017-01-01

    The heart is a central human organ and its diseases are the leading cause of death worldwide, but an in-depth knowledge of the identity and quantity of its constituent proteins is still lacking. Here, we determine the healthy human heart proteome by measuring 16 anatomical regions and three major...... level. Analysis of cardiac fibroblasts identifies cellular receptors as potential cell surface markers. Application of our heart map to atrial fibrillation reveals individually distinct mitochondrial dysfunctions. The heart map is available at maxqb.biochem.mpg.de as a resource for future analyses...... of normal heart function and disease....

  3. Effect of repeated intracoronary injection of bone marrow cells in patients with ischaemic heart failure the Danish stem cell study - congestive heart failure trial (DanCell-CHF)

    DEFF Research Database (Denmark)

    Diederichsen, A.C.; Møller, Jacob Eifer; Thayssen, P.

    2008-01-01

    was prospective and non-randomised, comprising an observational baseline period of 4 months followed by an interventional period of 12 months. Intracoronary bone marrow cell infusion was performed at the end of the baseline period and repeated 4 months later. RESULTS: 32 patients were included. LV ejection......, NYHA class improved (pnon-randomised study, no change in LV ejection fraction could be demonstrated after repeated intracoronary bone marrow stem cell treatment in patients with chronic ischaemic heart failure Udgivelsesdato: 2008/7...... repeated infusions would have additional positive effects. AIMS: To assess whether two treatments of intracoronary infusion of bone marrow stem cells, administered 4 months apart, could improve left ventricular (LV) systolic function in patients with chronic ischaemic heart failure. METHODS: The study...

  4. Advantages and disadvantages of using intravenous tissue Plasminogen activator as salvage therapy for inoperable HeartWare thrombosis.

    Science.gov (United States)

    Basken, Robyn; Bazzell, Charles M; Smith, Richard; Janardhanan, Rajesh; Khalpey, Zain

    2017-07-01

    Device thrombosis is a devastating complication of left ventricular assist devices. The definitive treatment has been device exchange or explant. Evidence of increasing morbidity and mortality with device exchange has shifted strategies toward conservative management. In this report, we detail the use of thrombolytics as salvage therapy in a patient with an occlusive HeartWare ventricular assist device (HeartWare Inc., Framingham, MA) thrombus, resulting in long-term survival without further intervention. © 2017 Wiley Periodicals, Inc.

  5. 'End-stage' heart failure therapy: potential lessons from congenital heart disease: from pulmonary artery banding and interatrial communication to parallel circulation.

    Science.gov (United States)

    Schranz, Dietmar; Akintuerk, Hakan; Voelkel, Norbert F

    2017-02-15

    The final therapy of 'end-stage heart failure' is orthotopic heart, lung or heart-lung transplantation. However, these options are not available for many patients worldwide. Therefore, novel therapeutical strategies are needed. Based on pathophysiological insights regarding (1) the long-term impact of an obstructive pulmonary outflow tract in neonates with congenitally corrected transposition of the great arteries, (2) the importance of a restrictive versus a non-restrictive atrial septum in neonates born with a borderline left ventricle and (3) the significance of both, a patent foramen ovale and/or open ductus arteriosus for survival of newborns with persistent pulmonary hypertension, the current review introduces some therapeutical strategies that may be applicable to selected patients with heart failure. These strategies include (1) reversible pulmonary artery banding in left ventricular-dilated cardiomyopathy with preserved right ventricular function, (2) the creation of restrictive interatrial communication to treat diastolic (systolic) heart failure, (3) atrioseptostomy or reverse Potts shunt in pulmonary arterial hypertension and (4) return to a fetal, parallel circulation by combining atrioseptostomy and reversed Potts shunt with or without placement of a bilateral pulmonary artery banding. While still being experimental, it is hoped that the procedures presented in the current overview will inspire future novel therapeutic strategies that may be applicable to selected patients with heart failure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  6. Does Long-Term Furosemide Therapy Cause Thiamine Deficiency in Patients with Heart Failure? A Focused Review.

    Science.gov (United States)

    Katta, Natraj; Balla, Sudarshan; Alpert, Martin A

    2016-07-01

    Diuretic therapy is a cornerstone in the management of heart failure. Most studies assessing body thiamine status have reported variable degrees of thiamine deficiency in patients with heart failure, particularly those treated chronically with high doses of furosemide. Thiamine deficiency in patients with heart failure seems predominantly to be due to increased urine volume and urinary flow rate. There is also evidence that furosemide may directly inhibit thiamine uptake at the cellular level. Limited data suggest that thiamine supplementation is capable of increasing left ventricular ejection fraction and improving functional capacity in patients with heart failure and a reduced left ventricular ejection fraction who were treated with diuretics (predominantly furosemide). Therefore, it may be reasonable to provide such patients with thiamine supplementation during heart failure exacerbations. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Adoptive T cell therapy: Addressing challenges in cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Yee Cassian

    2005-04-01

    Full Text Available Abstract Adoptive T cell therapy involves the ex vivo selection and expansion of effector cells for the treatment of patients with cancer. In this review, the advantages and limitations of using antigen-specific T cells are discussed in counterpoint to vaccine strategies. Although vaccination strategies represent more readily available reagents, adoptive T cell therapy provides highly selected T cells of defined phenotype, specificity and function that may influence their biological behavior in vivo. Adoptive T cell therapy offers not only translational opportunities but also a means to address fundamental issues in the evolving field of cancer immunotherapy.

  8. Stem Cell Therapy in Wound Healing and Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2016-08-01

    a novel approach to many diseases. SUMMARY: Wound healing therapies continue to rapidly evolve, with advances in basic science and engineering research heralding the development of new therapies, as well as ways to modify existing treatments. Stem cell-based therapy is one of the most promising therapeutic concepts for wound healing. Advances in stem cell biology have enabled researchers and clinicians alike with access to cells capable of actively modulating the healing response.  KEYWORDS: wound healing, tissue regeneration, stem cells therapy

  9. Predicting maximal HR in heart failure patients on β-blockade therapy.

    Science.gov (United States)

    Keteyian, Steven J; Kitzman, Dalane; Zannad, Faiez; Landzberg, Joel; Arnold, J Malcolm; Brubaker, Peter; Brawner, Clinton A; Bensimhon, Daniel; Hellkamp, Anne S; Ewald, Greg

    2012-03-01

    Standards for estimating maximal HR are important when interpreting the adequacy of physiologic stress during exercise testing, assessing chronotropic response, and prescribing an exercise training regimen. The equation 220 - age is used to estimate maximum HR; however, it overestimates measured maximal HR in patients taking β-adrenergic blockade (βB) therapy. This study developed and validated a practical equation to predict maximal HR in patients with heart failure (HF) taking βB therapy. Data from symptom-limited exercise tests completed on patients with systolic HF participating in the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training trial and taking a βB agent were used to develop a simplified equation, which was validated using bootstrapping. The simplified derived equation was 119 + 0.5 (resting HR) - 0.5 (age) - (0, if test was completed using a treadmill; 5, if using a stationary bike). The R2 and SEE were 0.28 and 18 beats·min(-1), respectively. Validation of this equation yielded a mean R and SEE of 0.28 and 18 beats·min(-1), respectively. For the equation 220 - age, the R2 was -2.93, and the SEE was 43 beats·min(-1). We report a valid and simple population-specific equation for estimating peak HR in patients with HF taking βB therapy. This equation should be helpful when evaluating chronotropic response or assessing if a maximum effort was provided during exercise testing. We caution, however, that the magnitude of the variation (SEE = 18 beats·min(-1)) associated with this prediction equation may make it impractical when prescribing exercise intensity.

  10. Differential heart rate response to magnetic seizure therapy (MST) relative to electroconvulsive therapy: a nonhuman primate model.

    Science.gov (United States)

    Rowny, Stefan B; Cycowicz, Yael M; McClintock, Shawn M; Truesdale, Matthew D; Luber, Bruce; Lisanby, Sarah H

    2009-09-01

    Electroconvulsive therapy (ECT) is an effective treatment for severe depression; however, the induced therapeutic seizure acts on the autonomic nervous system and results in significant cardiac effects. This is an important consideration particularly in the elderly. Magnetic seizure therapy (MST) is in development as a less invasive alternative, but its effects on cardiac function have not been studied. We sought to model those effects in nonhuman primates to inform the development of safer neurostimulation interventions. Twenty four rhesus monkeys were randomly assigned to receive 6 weeks of daily treatment with electroconvulsive stimulation (ECS), magnetic seizure therapy (MST) or anesthesia-alone sham. Digitally acquired ECG and an automated R-wave and inter-R interval (IRI) sampling were used to measure intervention effects on heart rate (HR). Significant differences between experimental conditions were found in the HR as evidenced by changes in the immediate post-stimulus, ictal and postictal epochs. Immediate post-stimulus bradycardia was seen with ECS but not with MST. ECS induced significantly more tachycardia than MST or sham in both the ictal and postictal periods. MST resulted in a small, but statistically significant increase in HR during the postictal period relative to baseline. HR was found to increase by 25% and 8% in the ECS and MST conditions, respectively. MST resulted in significantly less marked sympathetic and parasympathetic response than did ECS. This differential physiological response is consistent with MST having a more superficial cortical site of action with less impact on deeper brain structures implicated in cardiac control relative to ECT. The clinical relevance of the topographical seizure spread of MST and its associated effects on the autonomic nervous system remain to be determined in human clinical trials.

  11. Mesenchymal stem cell therapy for liver fibrosis.

    Science.gov (United States)

    Eom, Young Woo; Shim, Kwang Yong; Baik, Soon Koo

    2015-09-01

    Currently, the most effective treatment for end-stage liver fibrosis is liver transplantation; however, transplantation is limited by a shortage of donor organs, surgical complications, immunological rejection, and high medical costs. Recently, mesenchymal stem cell (MSC) therapy has been suggested as an effective alternate approach for the treatment of hepatic diseases. MSCs have the potential to differentiate into hepatocytes, and therapeutic value exists in their immune-modulatory properties and secretion of trophic factors, such as growth factors and cytokines. In addition, MSCs can suppress inflammatory responses, reduce hepatocyte apoptosis, increase hepatocyte regeneration, regress liver fibrosis and enhance liver functionality. Despite these advantages, issues remain; MSCs also have fibrogenic potential and the capacity to promote tumor cell growth and oncogenicity. This paper summarizes the properties of MSCs for regenerative medicine and their therapeutic mechanisms and clinical application in the treatment of liver fibrosis. We also present several outstanding risks, including their fibrogenic potential and their capacity to promote pre-existing tumor cell growth and oncogenicity.

  12. Cardiac Transplantation Followed by Dose-Intensive Melphalan and Autologous Stem Cell Transplantation for AL Amyloidosis and Heart Failure

    Science.gov (United States)

    Dey, Bimalangshu R; Chung, Stephen S; Spitzer, Thomas R; Zheng, Hui; MacGillivray, Thomas E.; Seldin, David C; McAfee, Steven; Ballen, Karen; Attar, Eyal; Wang, Thomas; Shin, Jordan; Newton-Cheh, Christopher; Moore, Stephanie; Sanchorawala, Vaishali; Skinner, Martha; Madsen, Joren C.; Semigran, Marc J.

    2010-01-01

    Background Patients with AL amyloidosis who present with severe heart failure due to cardiac involvement rarely survive more than six months. Survival after cardiac transplantation is markedly reduced due to the progression of amyloidosis. Autologous stem cell transplantation (ASCT) has become a common therapy for AL amyloidosis, but there is an exceedingly high treatment-related mortality in patients with heart failure. Methods We developed a treatment strategy of cardiac transplant followed by ASCT. 26 patients were evaluated, and of 18 eligible patients, nine patients underwent cardiac transplantation. Eight of these patients subsequently received an ASCT. Results Six of seven evaluable patients achieved a complete hematologic remission, and one achieved a partial remission. At a median follow-up of 56 months from cardiac transplant, five of seven patients are alive without recurrent amyloidosis. Their survival is comparable to 17,389 patients who received heart transplants for non-amyloid heart disease: 64% in non-amyloid vs. 60% in amyloid patients at seven years (p= 0.83). Seven of eight transplanted patients have had no evidence of amyloid in their cardiac allograft. Conclusions This demonstrates that cardiac transplantation followed by ASCT is feasible in selected patients with AL amyloidosis and heart failure, and that such a strategy may lead to improved overall survival. (clinicaltrials.gov, NCT00456040) PMID:20733534

  13. Dental stem cells: a future asset of ocular cell therapy.

    Science.gov (United States)

    Yam, Gary Hin-Fai; Peh, Gary Swee-Lim; Singhal, Shweta; Goh, Bee-Tin; Mehta, Jodhbir S

    2015-11-10

    Regenerative medicine using patient's own stem cells (SCs) to repair dysfunctional tissues is an attractive approach to complement surgical and pharmacological treatments for aging and degenerative disorders. Recently, dental SCs have drawn much attention owing to their accessibility, plasticity and applicability for regenerative use not only for dental, but also other body tissues. In ophthalmology, there has been increasing interest to differentiate dental pulp SC and periodontal ligament SC (PDLSC) towards ocular lineage. Both can commit to retinal fate expressing eye field transcription factors and generate rhodopsin-positive photoreceptor-like cells. This proposes a novel therapeutic alternative for retinal degeneration diseases. Moreover, as PDLSC shares similar cranial neural crest origin and proteoglycan secretion with corneal stromal keratoctyes and corneal endothelial cells, this offers the possibility of differentiating PDLSC to these corneal cell types. The advance could lead to a shift in the medical management of corneal opacities and endothelial disorders from highly invasive corneal transplantation using limited donor tissue to cell therapy utilizing autologous cells. This article provides an overview of dental SC research and the perspective of utilizing dental SCs for ocular regenerative medicine.

  14. Nanomedicine-mediated cancer stem cell therapy.

    Science.gov (United States)

    Shen, Song; Xia, Jin-Xing; Wang, Jun

    2016-01-01

    Circumstantial evidence suggests that most tumours are heterogeneous and contain a small population of cancer stem cells (CSCs) that exhibit distinctive self-renewal, proliferation and differentiation capabilities, which are believed to play a crucial role in tumour progression, drug resistance, recurrence and metastasis in multiple malignancies. Given that the existence of CSCs is a primary obstacle to cancer therapy, a tremendous amount of effort has been put into the development of anti-CSC strategies, and several potential approaches to kill therapeutically-resistant CSCs have been explored, including inhibiting ATP-binding cassette transporters, blocking essential signalling pathways involved in self-renewal and survival of CSCs, targeting CSCs surface markers and destroying the tumour microenvironment. Meanwhile, an increasing number of therapeutic agents (e.g. small molecule drugs, nucleic acids and antibodies) to selectively target CSCs have been screened or proposed in recent years. Drug delivery technology-based approaches hold great potential for tackling the limitations impeding clinical applications of CSC-specific agents, such as poor water solubility, short circulation time and inconsistent stability. Properly designed nanocarrier-based therapeutic agents (or nanomedicines) offer new possibilities of penetrating CSC niches and significantly increasing therapeutic drug accumulation in CSCs, which are difficult for free drug counterparts. In addition, intelligent nanomedicine holds great promise to overcome pump-mediated multidrug resistance which is driven by ATP and to decrease detrimental effects on normal somatic stem cells. In this review, we summarise the distinctive biological processes related to CSCs to highlight strategies against inherently drug-resistant CSCs. We then focus on some representative examples that give a glimpse into state-of-the-art nanomedicine approaches developed for CSCs elimination. A perspective on innovative therapeutic

  15. Towards stem-cell therapy in the endocrine pancreas

    NARCIS (Netherlands)

    Gangaram-Panday, Shanti T.; Faas, Marijke M.; de Vos, Paul

    Many approaches of stem-cell therapy for the treatment of diabetes have been described. One is the application of stem cells for replacement of nonfunctional islet cells in the native endogenous pancreas; another one is the use of stem cells as an inexhaustible source for islet-cell transplantation.

  16. Isolation and characterization of CD276+/HLA-E+ human subendocardial mesenchymal stem cells from chronic heart failure patients: analysis of differentiative potential and immunomodulatory markers expression.

    Science.gov (United States)

    Anzalone, Rita; Corrao, Simona; Lo Iacono, Melania; Loria, Tiziana; Corsello, Tiziana; Cappello, Francesco; Di Stefano, Antonino; Giannuzzi, Pantaleo; Zummo, Giovanni; Farina, Felicia; La Rocca, Giampiero

    2013-01-01

    Mesenchymal stem cells (MSCs) are virtually present in all postnatal organs as well as in perinatal tissues. MSCs can be differentiated toward several mature cytotypes and interestingly hold potentially relevant immunomodulatory features. Myocardial infarction results in severe tissue damage, cardiomyocyte loss, and eventually heart failure. Cellular cardiomyoplasty represents a promising approach for myocardial repair. Clinical trials using MSCs are underway for a number of heart diseases, even if their outcomes are hampered by low long-term improvements and the possible presence of complications related to cellular therapy administration. Therefore, elucidating the presence and role of MSCs that reside in the post-infarct human heart should provide essential alternatives for therapy. In the current article we show a novel method to reproducibly isolate and culture MSCs from the subendocardial zone of human left ventricle from patients undergoing heart transplant for post-infarct chronic heart failure (HSE-MSCs, human subendocardial mesenchymal stem cells). By using both immunocytochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR), we demonstrated that these cells do express key MSCs markers and do express heart-specific transcription factors in their undifferentiated state, while lacking strictly cardiomyocyte-specific proteins. Moreover, these cells do express immunomodulatory molecules that should disclose their further potential in immune modulation processes in the post-infarct microenvironment. Another novel datum of potentially relevant interest is the expression of cardiac myosin heavy chain at nucclear level in HSE-MSCs. Standard MSCs trilineage differentiation experiments were also performed. The present paper adds new data on the basic biological features of heart-resident MSCs that populate the organ following myocardial infarction. The use of heart-derived MSCs to promote in-organ repair or as a cellular source for cardiomyoplasty

  17. [Dendritic cells and coronary collateral circulation in coronary heart disease].

    Science.gov (United States)

    Li, Chuanchang; Liu, Wei; Yi, Jun; Li, Zhenyu; Pu, Xiaoqun; Yang, Tianlun; Xie, Qiying; Mo, Long; Chen, Xiaobin

    2010-05-01

    To determine the relationship between the number,phenotype and functional status of dendritic cells (DCs) and coronary collateral circulation (CCC) in coronary heart disease (CHD). Forty patients with severe coronary stenosis were recruited and divided into a CCC formation group (Group A, n=22) and a non-CCC formation group (Group B, n=18). Density gradient centrifugation was applied to separate the mononuclear cells (MNCs) from coronary artery blood samples, and MNCs were cultured and proliferated in vitro. The morphology of DCs was observed under converted microscope. The number of harvested cells and DCs was counted by hematocytometer. Flow cytometry was applied to investigate the phenotype and the mean fluorescence intensity (MFI). Mixed lymphocyte reaction was used to test the function of DCs to stimulate the proliferation of T lymphocytes. Stimulation index (SI) was calculated and compared. (1) After in vitro proliferation, DCs were cultured successfully from the mononuclear cells from coronary artery blood samples and the morphology of DCs was not different in the 2 groups. (2) The number of mononuclear cells (MNC no) was (3.95+/-1.41)*10(6), in the CCC group and (2.76+/-0.92)*10(6) in the non-CCC group. The MNC number was significantly increased in the CCC group (P=0.003). (3) The number of DCs was (1.54+/-0.96)*10(6) in the CCC group, and (0.99+/-0.46)*10(6) in the non-CCC group (P=0.033). (4)There was no statistical significance in the percent of CD1a+, CD1a+CD80+, CD1a+CD83+, CD1a+CD86+ cells, and MFI in the 2 groups (P>0.05). (5) SI was 4.96+/-2.30 in the CCC group, whereas 2.66+/-1.04 in the non-CCC group. The SI in the CCC group increased significantly(P=0.0003). In CHD patients with severe coronary stenosis, patients with CCC formation have higher number of DCs and stronger potential of T lymphocyte stimulation.

  18. Cancer stem cell targeted therapy: progress amid controversies

    Science.gov (United States)

    Wang, Tao; Shigdar, Sarah; Gantier, Michael P.; Hou, Yingchun; Wang, Li; Li, Yong; Shamaileh, Hadi Al; Yin, Wang; Zhou, Shu-Feng; Zhao, Xinhan; Duan, Wei

    2015-01-01

    Although cancer stem cells have been well characterized in numerous malignancies, the fundamental characteristics of this group of cells, however, have been challenged by some recent observations: cancer stem cells may not necessary to be rare within tumors; cancer stem cells and non-cancer stem cells may undergo reversible phenotypic changes; and the cancer stem cells phenotype can vary substantially between patients. Here the current status and progresses of cancer stem cells theory is illustrated and via providing a panoramic view of cancer therapy, we addressed the recent controversies regarding the feasibility of cancer stem cells targeted anti-cancer therapy. PMID:26496035

  19. Aerobic Exercise as an Adjunct Therapy for Improving Cognitive Function in Heart Failure

    Directory of Open Access Journals (Sweden)

    Rebecca A. Gary

    2014-01-01

    Full Text Available Persons with heart failure (HF are typically older and are at a much higher risk for developing cognitive impairment (CI than persons without HF. Increasingly, CI is recognized as a significant, independent predictor of worse clinical outcomes, more frequent hospital readmissions, and higher mortality rates in persons with HF. CI can have devastating effects on ability to carry out HF effective self-care behaviors. If CI occurs, however, there are currently no evidence based guidelines on how to manage or improve cognitive function in this population. Improvement in cognition has been reported following some therapies in HF and is thought to be the consequence of enhanced cerebral perfusion and oxygenation, suggesting that CI may be amenable to intervention. Because there is substantial neuronal loss with dementia and no effective restorative therapies, interventions that slow, reverse, or prevent cognitive decline are essential. Aerobic exercise is documented to increase cerebral perfusion and oxygenation by promoting neuroplasticity and neurogenesis and, in turn, cognitive functioning. Few studies have examined exercise as a potential adjunct therapy for attenuating or alleviating cognitive decline in HF. In this review, the potential benefit of aerobic exercise on cognitive functioning in HF is presented along with future research directions.

  20. Immunosuppressive therapies after heart transplantation--The balance between under- and over-immunosuppression.

    Science.gov (United States)

    Söderlund, Carl; Rådegran, Göran

    2015-07-01

    Since the first heart transplantation (HT) in 1967, survival has steadily improved. Issues related to over- and under-immunosuppression are, however, still common following HT. Whereas under-immunosuppression may result in rejection, over-immunosuppression may render other medical problems, including infections, malignancies and chronic kidney disease (CKD). As such complications constitute major limiting factors for long-term survival following HT, identifying improved diagnostic and preventive methods has been the focus of many studies. Notably, research on antibody-mediated rejection (AMR) and cardiac allograft vasculopathy (CAV) has recently led to the development of nomenclatures that may aid in their diagnosis and treatment. Moreover, novel immunosuppressants (such as mammalian target of rapamycin [m-TOR] inhibitors) and strategies aimed at minimizing the use of calcineurin inhibitors (CNIs) and corticosteroids (CSs), have provided alternatives to the traditional combination maintenance immunosuppressive therapy of CSs, cyclosporine (CSA) or tacrolimus (TAC), and azathioprine (AZA) or mycophenolate mofetil (MMF). Research within this field of medicine is not only extensive, but also in constant progress. The purpose of the present review was therefore to summarize some major points regarding immunosuppressive therapies after HT and the balance between under- and over-immunosuppression. Transplant immunology, rejection, common medical problems related to over-immunosuppression, as well as induction and maintenance immunosuppressive drugs and therapies, are addressed. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Angiopoietin-1-expressing adipose stem cells genetically modified with baculovirus nanocomplex: investigation in rat heart with acute infarction.

    Science.gov (United States)

    Paul, Arghya; Nayan, Madhur; Khan, Afshan Afsar; Shum-Tim, Dominique; Prakash, Satya

    2012-01-01

    The objective of this study was to develop angiopoietin-1 (Ang1)-expressing genetically modified human adipose tissue derived stem cells (hASCs) for myocardial therapy. For this, an efficient gene delivery system using recombinant baculovirus complexed with cell penetrating transactivating transcriptional activator TAT peptide/deoxyribonucleic acid nanoparticles (Bac-NP), through ionic interactions, was used. It was hypothesized that the hybrid Bac- NP(Ang1) system can efficiently transduce hASCs and induces favorable therapeutic effects when transplanted in vivo. To evaluate this hypothesis, a rat model with acute myocardial infarction and intramyocardially transplanted Ang1-expressing hASCs (hASC-Ang1), genetically modified by Bac-NP(Ang1), was used. Ang1 is a crucial pro-angiogenic factor for vascular maturation and neovasculogenesis. The released hAng1 from hASC-Ang1 demonstrated profound mitotic and anti-apoptotic activities on endothelial cells and cardiomyocytes. The transplanted hASC-Ang1 group showed higher cell retention compared to hASC and control groups. A significant increase in capillary density and reduction in infarct sizes were noted in the infarcted hearts with hASC-Ang1 treatment compared to infarcted hearts treated with hASC or the untreated group. Furthermore, the hASC-Ang1 group showed significantly higher cardiac performance in echocardiography (ejection fraction 46.28% ± 6.3%, P < 0.001 versus control, n = 8) than the hASC group (36.35% ± 5.7%, P < 0.01, n = 8), 28 days post-infarction. The study identified Bac-NP complex as an advanced gene delivery vehicle for stem cells and demonstrated its potential to treat ischemic heart disease with high therapeutic index for combined stem cell-gene therapy strategy.

  2. From beat rate variability in induced pluripotent stem cell-derived pacemaker cells to heart rate variability in human subjects.

    Science.gov (United States)

    Ben-Ari, Meital; Schick, Revital; Barad, Lili; Novak, Atara; Ben-Ari, Erez; Lorber, Avraham; Itskovitz-Eldor, Joseph; Rosen, Michael R; Weissman, Amir; Binah, Ofer

    2014-10-01

    We previously reported that induced pluripotent stem cell-derived cardiomyocytes manifest beat rate variability (BRV) resembling heart rate variability (HRV) in the human sinoatrial node. We now hypothesized the BRV-HRV continuum originates in pacemaker cells. To investigate whether cellular BRV is a source of HRV dynamics, we hypothesized 3 levels of interaction among different cardiomyocyte entities: (1) single pacemaker cells, (2) networks of electrically coupled pacemaker cells, and (3) the in situ sinoatrial node. We measured BRV/HRV properties in single pacemaker cells, induced pluripotent stem cell-derived contracting embryoid bodies (EBs), and electrocardiograms from the same individual. Pronounced BRV/HRV was present at all 3 levels. The coefficient of variance of interbeat intervals and Poincaré plot indices SD1 and SD2 for single cells were 20 times greater than those for EBs (P heart (the latter two were similar; P > .05). We also compared BRV magnitude among single cells, small EBs (~5-10 cells), and larger EBs (>10 cells): BRV indices progressively increased with the decrease in the cell number (P heart rhythm. The decreased BRV magnitude in transitioning from the single cell to the EB suggests that the HRV of in situ hearts originates from the summation and integration of multiple cell-based oscillators. Hence, complex interactions among multiple pacemaker cells and intracellular Ca(2+) handling determine HRV in humans and cardiomyocyte networks. Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  3. Omentum-derived stromal cells improve myocardial regeneration in pig post-infarcted heart through a potent paracrine mechanism

    Energy Technology Data Exchange (ETDEWEB)

    De Siena, Rocco; Balducci, Luigi; Blasi, Antonella; Montanaro, Manuela Gessica; Saldarelli, Marilisa [Medestea Research and Production Laboratories, Consorzio Carso, 70010 Valenzano, Bari (Italy); Saponaro, Vittorio [Department of Veterinary Medicine, University of Bari, 70010 Valenzano, Bari (Italy); Martino, Carmela [Medestea Research and Production Laboratories, Consorzio Carso, 70010 Valenzano, Bari (Italy); Logrieco, Gaetano [Department of Surgery, Hospital ' F. Miulli' 70021 AcquaViva delle Fonti, Bari (Italy); Soleti, Antonio; Fiobellot, Simona [Medestea Research and Production Laboratories, Consorzio Carso, 70010 Valenzano, Bari (Italy); Madeddu, Paolo [Experimental Cardiovascular Medicine, Bristol Heart Institute, Bristol BS2 8WH (United Kingdom); Rossi, Giacomo [Department of Pathology, University of Camerino, 63100 Ascoli Piceno (Italy); Ribatti, Domenico [Department of Human Anatomy, University of Bari, 70125 Bari (Italy); Crovace, Antonio [Department of Veterinary Medicine, University of Bari, 70010 Valenzano, Bari (Italy); Cristini, Silvia; Invernici, Gloria; Parati, Eugenio Agostino [Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, Fondazione IRCCS Neurological Institute ' Carlo Besta' , 20133 Milan (Italy); Alessandri, Giulio, E-mail: cisiamo2@yahoo.com [Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, Fondazione IRCCS Neurological Institute ' Carlo Besta' , 20133 Milan (Italy)

    2010-07-01

    Cell-based therapy could be a valid option to treat myocardial infarct (MI). Adipose-derived stromal cells (ADStCs) have demonstrated tissue regenerative potential including cardiomyogenesis. Omentum is an extremely rich source of visceral fat and its accumulation seems to correlate with cardiovascular diseases. We investigated the capacity of human fat Omentum-derived StCs (FOStCs) to affect heart function upon acute infarct in pigs induced by permanent ligation of the anterior interventricular artery (IVA). We demonstrated for the first time that the local injection of 50 x 10{sup 6} of FOStCs ameliorates the functional parameters of post-infarct heart. Most importantly, histology of FOStCs treated hearts demonstrated a substantial improvement of cardiomyogenesis. In culture, FOStCs produced an impressive number and amount of angiogenic factors and cytokines. Moreover, the conditioned medium of FOStCs (FOStCs-CM) stimulates in vitro cardiac endothelial cells (ECs) proliferation and vascular morphogenesis and inhibits monocytes, EC activation and cardiomyocyte apoptosis. Since FOStCs in vivo did not trans-differentiate into cardiomyocyte-like cells, we conclude that FOStCs efficacy was presumably mediated by a potent paracrine mechanism involving molecules that concomitantly improved angiogenesis, reduced inflammation and prevented cardiomyocytes death. Our results highlight for the first time the important role that human FOStCs may have in cardiac regeneration.

  4. Omentum-derived stromal cells improve myocardial regeneration in pig post-infarcted heart through a potent paracrine mechanism.

    Science.gov (United States)

    De Siena, Rocco; Balducci, Luigi; Blasi, Antonella; Montanaro, Manuela Gessica; Saldarelli, Marilisa; Saponaro, Vittorio; Martino, Carmela; Logrieco, Gaetano; Soleti, Antonio; Fiobellot, Simona; Madeddu, Paolo; Rossi, Giacomo; Ribatti, Domenico; Crovace, Antonio; Cristini, Silvia; Invernici, Gloria; Parati, Eugenio Agostino; Alessandri, Giulio

    2010-07-01

    Cell-based therapy could be a valid option to treat myocardial infarct (MI). Adipose-derived stromal cells (ADStCs) have demonstrated tissue regenerative potential including cardiomyogenesis. Omentum is an extremely rich source of visceral fat and its accumulation seems to correlate with cardiovascular diseases. We investigated the capacity of human fat Omentum-derived StCs (FOStCs) to affect heart function upon acute infarct in pigs induced by permanent ligation of the anterior interventricular artery (IVA). We demonstrated for the first time that the local injection of 50x10(6) of FOStCs ameliorates the functional parameters of post-infarct heart. Most importantly, histology of FOStCs treated hearts demonstrated a substantial improvement of cardiomyogenesis. In culture, FOStCs produced an impressive number and amount of angiogenic factors and cytokines. Moreover, the conditioned medium of FOStCs (FOStCs-CM) stimulates in vitro cardiac endothelial cells (ECs) proliferation and vascular morphogenesis and inhibits monocytes, EC activation and cardiomyocyte apoptosis. Since FOStCs in vivo did not trans-differentiate into cardiomyocyte-like cells, we conclude that FOStCs efficacy was presumably mediated by a potent paracrine mechanism involving molecules that concomitantly improved angiogenesis, reduced inflammation and prevented cardiomyocytes death. Our results highlight for the first time the important role that human FOStCs may have in cardiac regeneration.

  5. Insulin therapy improves insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease

    DEFF Research Database (Denmark)

    Rask-Madsen, C; Ihlemann, N; Krarup, T

    2001-01-01

    Blunted insulin-stimulated endothelial function may be a mechanism for the development of atherothrombotic disease in type 2 diabetes, but it is unknown whether hypoglycemic drug therapy can modulate this abnormality. We studied patients with type 2 diabetes and stable ischemic heart disease (n......, and 69 +/- 36% (P = 0.0002). In the time control group, insulin stimulation remained without effect after 8 weeks (P = 0.7). In conclusion, insulin therapy partly restores insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease....... after intrabrachial infusion of insulin. Patients were restudied after 2 months of insulin therapy with four daily subcutaneous injections (treatment group, n = 19) or without hypoglycemic drug therapy (time control group, n = 9). Insulin infusion raised venous serum insulin in the forearm to high...

  6. Evaluation of antihypertensive therapy in diabetic hypertensive patients: impact of ischemic heart disease

    Directory of Open Access Journals (Sweden)

    Shraim NY

    2009-03-01

    Full Text Available Macrovascular complications are common in diabetic hypertensive patients. Appropriate antihypertensive therapy and tight blood pressure control are believed to prevent or delay such complication. Objective: To evaluate utilization patterns of antihypertensive agents and blood pressure (BP control among diabetic hypertensive patients with and without ischemic heart disease (IHD. Methods: Retrospective cohort study of all diabetic hypertensive patients attending Al-watani medical center from August 2006 until August 2007. Proportions of use of different antihypertensive drug classes were compared for all patients receiving 1, 2, 3, or 4 or more drugs, and separately among patients with and without IHD. Blood pressure control (equal or lower 130/80 mmHg was compared for patients receiving no therapy, monotherapy, or combination therapy and separately among patients with and without IHD. Results: 255 patients were included in the study; their mean age was 64.4 (SD=11.4 years. Sixty one (23.9% of the included patients was on target BP. Over 60% of the total patients were receiving angiotensin-converting enzyme inhibitors (ACEI/ angiotensin receptor blocker (ARB, followed by diuretics (40.8%, calcium channel blockers (25.1% and beta-blockers (12.5%. The majority (> 55% of patients were either on mono or no drug therapy. More than 55% of patients with controlled BP were using ACE-I. More than half (50.8% of the patients with controlled BP were on combination therapy while 42.3% of patients with uncontrolled BP were on combination therapy (p=0.24. More patient in the IHD achieved target BP than those in non-IHD group (p=0.019. Comparison between IHD and non-IHD groups indicated no significant difference in the utilization of any drug class with ACE-I being the most commonly utilized in both groups. Conclusions: Patterns of antihypertensive therapy were generally but not adequately consistent with international guidelines. Areas of improvement include

  7. Present and future of allogeneic natural killer cell therapy

    Directory of Open Access Journals (Sweden)

    Okjae eLim

    2015-06-01

    Full Text Available Natural killer (NK cells are innate lymphocytes that are capable of eliminating tumor cells and are therefore used for cancer therapy. Although many early investigators used autologous NK cells, including lymphokine-activated killer cells, the clinical efficacies were not satisfactory. Meanwhile, human leukocyte antigen (HLA-haploidentical hematopoietic stem cell transplantation revealed the anti-tumor effect of allogeneic NK cells, and HLA-haploidentical, killer cell immunoglobulin-like receptor (KIR ligand-mismatched allogeneic NK cells are currently used for many protocols requiring NK cells. Moreover, allogeneic NK cells from non-HLA-related healthy donors have been recently used in cancer therapy. The use of allogeneic NK cells from non-HLA-related healthy donors allows the selection of donor NK cells with higher flexibility and to prepare expanded, cryopreserved NK cells for instant administration without delay for ex vivo expansion. In cancer therapy with allogeneic NK cells, optimal matching of donors and recipients is important to maximize the efficacy of the therapy. In this review, we summarize the present state of allogeneic NK cell therapy and its future directions.

  8. Three-dimensional image reconstruction of distribution of Pnmt+ cell-derived cells in murine heart.

    Science.gov (United States)

    Ni, Haibo; Wang, Yange; Crawford, William; Zhang, Shanzhuo; Cheng, Longxian; Zhang, Henggui; Lei, Ming

    2017-09-26

    Elucidating the function of specific cell types in a highly complex multicellular system such as the heart often requires detailed anatomic reconstruction. We recently described a distinctive class of phenylethanolamine n-methyltransferase (Pnmt+) cell-derived cardiomyocytes (PdCMs), a new cardiomyocyte population with a potential endocrine role. In this dataset, a 3D reconstruction was carried out to visualise the distribution of PdCMs throughout the murine heart. Rigid registration (stiff rotation and translation) was applied to properly align the fused heart slice images based on landmarks using TrakEM2, an open source plug-in in Fiji. The registered slices were then analysed and reconstructed using MATLAB (MATLAB®. Version 8.3.0.532). The final reconstructed 3D volume was 561×866×48 pixels (corresponding to spatial resolutions of 5.8, 8.9 and 2.5 mm in the x-, y- and z-direction respectively), and visualised in Paraview. The reconstruction allows for detailed analyses of morphology, projections and cellular features of different cell types, enabling further geometrical and topological analyses. Image data can be accessed and viewed through Figshare.

  9. Relationship Between Reverse Remodeling and Cardiopulmonary Exercise Capacity in Heart Failure Patients Undergoing Cardiac Resynchronization Therapy

    DEFF Research Database (Denmark)

    Mastenbroek, Mirjam H; Sant, Jetske Van't; Versteeg, Henneke

    2016-01-01

    BACKGROUND: Studies on the relationship between left ventricular reverse remodeling and cardiopulmonary exercise capacity in heart failure patients undergoing cardiac resynchronization therapy (CRT) are scarce and inconclusive. METHODS AND RESULTS: Eighty-four patients with a 1st-time CRT...... response (left ventricular end-systolic volume decrease ≥15%) and a comprehensive set of CPX results was examined. Echocardiographic responders (54%) demonstrated higher peak oxygen consumption and better exercise performance than nonresponders at baseline and at 6-month follow-up. Furthermore, only...... correlates of higher average oxygen consumption during exercise, and that nonischemic etiology and smaller pre-implantation QRS width were associated with better ventilatory efficiency over time. CONCLUSIONS: During the first 6 months of CRT there was a significant positive association between reverse...

  10. Successful Posaconazole Therapy of Disseminated Alternariosis due to Alternaria infectoria in a Heart Transplant Recipient.

    Science.gov (United States)

    Lyskova, Pavlina; Kubanek, Milos; Hubka, Vit; Sticova, Eva; Voska, Ludek; Kautznerova, Dana; Kolarik, Miroslav; Hamal, Petr; Vasakova, Martina

    2017-04-01

    We report a case of phaeohyphomycosis caused by Alternaria infectoria in a 61-year-old heart transplant recipient with multiple skin lesions and pulmonary infiltrates. The infection spread via the haematogenous route from the primary cutaneous lesions into the lungs. The diagnosis was based on the histopathological examination, direct microscopy, skin lesion cultures and detection of Alternaria DNA in the bronchoalveolar lavage fluid using molecular methods. The treatment consisted of a combination of surgical excision and systemic antifungal therapy. Voriconazole was the first agent used but had a weak effect. Posaconazole was subsequently used to achieve a successful response. The isolate was identified as A. infectoria by sequencing of the rDNA ITS region and the partial β-tubulin gene.

  11. Cardio-oncology Related to Heart Failure: Epidermal Growth Factor Receptor Target-Based Therapy.

    Science.gov (United States)

    Kenigsberg, Benjamin; Jain, Varun; Barac, Ana

    2017-04-01

    Cancer therapy targeting the epidermal growth factor receptor (EGFR)/erythroblastic leukemia viral oncogene B (ErbB)/human EGFR receptor (HER) family of tyrosine kinases has been successfully used in treatment of several malignancies. The ErbB pathways play a role in the maintenance of cardiac homeostasis. This article summarizes current knowledge about EGFR/ErbB/HER receptor-targeted cancer therapeutics focusing on their cardiotoxicity profiles, molecular mechanisms, and implications in clinical cardio-oncology. The article discusses challenges in predicting, monitoring, and treating cardiac dysfunction and heart failure associated with ErbB-targeted cancer therapeutics and highlights opportunities for researchers and clinical investigators. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Combined Therapy with Desferal and Deferiprone in Improvement of Heart Function in Thalassemic Patients

    Directory of Open Access Journals (Sweden)

    Shahramian Iraj

    2010-03-01

    Full Text Available Background: Cardiac complications due to iron overload are the most common causes of death in patients with major thalassemia. This study assessed the efficacy of iron chelating by desferal-L1 in improvement of cardiac function in patients with major thalassemia.Methods and Materials: Patients older then 8 years old with major thalassemia that were admitted to hematology ward of Ali-e-Asghar hospital of Zahedan in 2005-2006 and had lower than normal diastolic indices in annual echocardiography were considered as study population. During primary tests, indices of diastolic function of left and right hearts were calculated, using echocardiography with 2D, M-mode and Doppler then the patients were placed on a combination of desferal (30-40mg/kg/day two nights per week and L1 (deferiprone (75mg/kg/day, three times a day. At the end of the study, cardiac indices were calculated again. Data were using SPSS software and paired t-test and P0.05. Systolic indices of left ventricule increased significantly after treatment (P<0.05.Conclusion: In this study, after one year of treatment with a combination of desferal-L1 in patients with major thalassemia, echocardiography showed improvement in left heart systolic and diastolic function. This combination therapy prevented progression of right ventricular diastolic function abnormality

  13. Intra-myocardial biomaterial injection therapy in the treatment of heart failure: Materials, outcomes and challenges.

    Science.gov (United States)

    Nelson, Devin M; Ma, Zuwei; Fujimoto, Kazuro L; Hashizume, Ryotaro; Wagner, William R

    2011-01-01

    Heart failure initiated by coronary artery disease and myocardial infarction (MI) is a widespread, debilitating condition for which there are a limited number of options to prevent disease progression. Intra-myocardial biomaterial injection following MI theoretically provides a means to reduce the stresses experienced by the infarcted ventricular wall, which may alter the pathological remodeling process in a positive manner. Furthermore, biomaterial injection provides an opportunity to concurrently introduce cellular components and depots of bioactive agents. Biologically derived, synthetic and hybrid materials have been applied, as well as materials designed expressly for this purpose, although optimal design parameters, including degradation rate and profile, injectability, elastic modulus and various possible bioactivities, largely remain to be elucidated. This review seeks to summarize the current body of growing literature where biomaterial injection, with and without concurrent pharmaceutical or cellular delivery, has been pursued to improve functional outcomes following MI. The literature to date generally demonstrates acute functional benefits associated with biomaterial injection therapy across a broad variety of animal models and material compositions. Further functional improvements have been reported when cellular or pharmaceutical agents have been incorporated into the delivery system. Despite these encouraging early results, the specific mechanisms behind the observed functional improvements remain to be fully explored and future studies employing hypothesis-driven material design and selection may increase the potential of this approach to alleviate the morbidity and mortality of heart failure. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  14. Stem Cell Therapy for Myocardial Infarction: Are We Missing Time?

    NARCIS (Netherlands)

    ter Horst, Kasper W.

    2010-01-01

    The success of stem cell therapy in myocardial infarction (MI) is modest, and for stem cell therapy to be clinically effective fine-tuning in regard to timing, dosing, and the route of administration is required. Experimental studies suggest the existence of a temporal window of opportunity bound by

  15. EFFECT OF SIMVASTATIN THERAPY ON INDICATORS OF TRANSMITRAL BLOOD FLOW IN PATIENTS WITH DIASTOLIC HEART FAILURE

    Directory of Open Access Journals (Sweden)

    T. V. Pinchuk

    2015-09-01

    Full Text Available Aim. To study the effect of simvastatin added to standard therapy on the left ventricular structure functional status in patients with diastolic chronic heart failure (CHF.Material and methods. Patients (n=125 with diastolic CHF (relaxation disturbances and pseudonormalization were included into the open nonrandomized study. Patients of the main group (n=66 received simvastatin additionally to standard therapy of CHF. Patients of control group (n=59 received standard therapy only. Initially and after 6 months of treatment Doppler echocardiography (EchoCG was performed with assessment of transmitral blood flow indices. On the basis of EchoCG data diastolic dysfunction types were determined in patients of the main group. Dynamics of EchoCG indices were evaluated in accordance with these types.Results. Significant increase in E (peak early diastolic left ventricular filling velocity value by 14.1% (p<0.001 and E/A (where A - peak left ventricular filling velocity at atrial contraction ratio by 18.7% (p<0.001 was found in the main group in estimating of transmitral flow indicators. Deceleration time of early diastolic filling significantly decreased by 7.8% (p<0.01. Other parameters did not change significantly both in the main and control groups. Intra-group comparison in the main group demonstrated that transmitral blood flow indices changed significantly only in patients with delayed relaxation (type I of diastolic dysfunction.Conclusion. Simvаstatin added to standard therapy of CHF resulted in significant improvement in the left ventricle diastolic function.

  16. Cardiac resynchronization therapy improves psycho-cognitive performance in patients with heart failure.

    Science.gov (United States)

    Duncker, David; Friedel, Katrin; König, Thorben; Schreyer, Hendrik; Lüsebrink, Ulrich; Duncker, Mareke; Oswald, Hanno; Klein, Gunnar; Gardiwal, Ajmal

    2015-09-01

    Reduced cognitive performance and high prevalence of depression have been reported in patients with congestive heart failure (CHF) and severe left ventricular dysfunction. However, effects of contemporary device therapy on cognitive performance and depression symptoms have not been studied thoroughly. Seventy-four consecutive CHF patients-45 receiving a biventricular defibrillator (CRT-D) and 29 receiving an implantable single or dual-chamber defibrillator (ICD) as a control group-were enrolled in this investigator-initiated, prospective, controlled, and investigator-blinded study. A set of neuropsychological tests (mini-mental state examination, DemTect, age-concentration test, and Beck depression inventory) was performed before, at 3 and at 6 months after device implantation. DemTect-score improved significantly (F = 7.8; P = 0.007) after CRT-D-implantation compared with ICD. Age-concentration test revealed better concentration ability after CRT-D-implantation (F = 8.3; P = 0.005) compared with ICD. Under CRT-D mini-mental state examination showed a significant improvement (F = 4.2; P = 0.043). CRT with defibrillator therapy also improved depression revealed by beck depression inventory (F = 14.7; P< 0.001) compared with ICD. This prospective study is the first to demonstrate psycho-cognitive improvement by resynchronization therapy in CHF patients with severe left ventricular dysfunction. In contrast to ICD therapy, the beneficial effect of CRT-D on psycho-cognitive performance might be attributed to improved cardiac function and haemodynamics. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  17. Effectiveness of the Anger Management Group Therapy on Sleep Quality and Anger among the Patients with Coronary Heart Diseases

    Directory of Open Access Journals (Sweden)

    Elham Radman

    2016-05-01

    Full Text Available Background and Objective: Coronary heart disease is one of the main causes of mortality that has a strong relationship with psychological problems specially anger. In addition, the quality of sleep is poor among the patients with coronary heart disease. Therefore, the aim of current study is to investigate the effectiveness of the anger management group therapy on sleep quality and anger among the patients with coronary heart diseases.Materials and Methods: This research was a quasi-experimental study with pre and post-tests. The 30 male patients with coronary heart diseases were selected with a convenience sampling method from Emam Jafare Sadegh’s Hospital in Aligodarz in 2014-2015. The participants were assigned randomly to the control and experimental groups. Anger management group therapy was conducted with the participation of experimental group during eight sessions (90 minutes per week. The research instruments were the Pittsburgh Sleep Quality Index (PSQI, and the State-Trait Anger Expression lnventory-2 (STAXI-2. Statistical analysis was conducted by using the analysis of variance.Results: The results indicated that there is a significant difference between means of sleep quality (P=0.001 and anger (P=0.001 by eliminating the effectiveness of pretest (P < 0.01.Conclusion: The Study showed that anger management group therapy with decreasing the level of anger and improving the sleep quality should be considered as a psychological intervention in patients with coronary heart disease.

  18. Capillary regeneration in scleroderma: stem cell therapy reverses phenotype?

    Directory of Open Access Journals (Sweden)

    Jo N Fleming

    2008-01-01

    Full Text Available Scleroderma is an autoimmune disease with a characteristic vascular pathology. The vasculopathy associated with scleroderma is one of the major contributors to the clinical manifestations of the disease.We used immunohistochemical and mRNA in situ hybridization techniques to characterize this vasculopathy and showed with morphometry that scleroderma has true capillary rarefaction. We compared skin biopsies from 23 scleroderma patients and 24 normal controls and 7 scleroderma patients who had undergone high dose immunosuppressive therapy followed by autologous hematopoietic cell transplant. Along with the loss of capillaries there was a dramatic change in endothelial phenotype in the residual vessels. The molecules defining this phenotype are: vascular endothelial cadherin, a supposedly universal endothelial marker required for tube formation (lost in the scleroderma tissue, antiangiogenic interferon alpha (overexpressed in the scleroderma dermis and RGS5, a signaling molecule whose expression coincides with the end of branching morphogenesis during development and tumor angiogenesis (also overexpressed in scleroderma skin. Following high dose immunosuppressive therapy, patients experienced clinical improvement and 5 of the 7 patients with scleroderma had increased capillary counts. It was also observed in the same 5 patients, that the interferon alpha and vascular endothelial cadherin had returned to normal as other clinical signs in the skin regressed, and in all 7 patients, RGS5 had returned to normal.These data provide the first objective evidence for loss of vessels in scleroderma and show that this phenomenon is reversible. Coordinate changes in expression of three molecules already implicated in angiogenesis or anti-angiogenesis suggest that control of expression of these three molecules may be the underlying mechanism for at least the vascular component of this disease. Since rarefaction has been little studied, these data may have

  19. Priming Mesenchymal Stem Cells with Endothelial Growth Medium Boosts Stem Cell Therapy for Systemic Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Lucas Felipe de Oliveira

    2015-01-01

    Full Text Available Systemic arterial hypertension (SAH, a clinical syndrome characterized by persistent elevation of arterial pressure, is often associated with abnormalities such as microvascular rarefaction, defective angiogenesis, and endothelial dysfunction. Mesenchymal stem cells (MSCs, which normally induce angiogenesis and improve endothelial function, are defective in SAH. The central aim of this study was to evaluate whether priming of MSCs with endothelial growth medium (EGM-2 increases their therapeutic effects in spontaneously hypertensive rats (SHRs. Adult female SHRs were administered an intraperitoneal injection of vehicle solution n=10, MSCs cultured in conventional medium (DMEM plus 10% FBS, n=11, or MSCs cultured in conventional medium followed by 72 hours in EGM-2 (pMSC, n=10. Priming of the MSCs reduced the basal cell death rate in vitro. The administration of pMSCs significantly induced a prolonged reduction (10 days in arterial pressure, a decrease in cardiac hypertrophy, an improvement in endothelium-dependent vasodilation response to acetylcholine, and an increase in skeletal muscle microvascular density compared to the vehicle and MSC groups. The transplanted cells were rarely found in the hearts and kidneys. Taken together, our findings indicate that priming of MSCs boosts stem cell therapy for the treatment of SAH.

  20. Long-term outcome of ablative therapy of postoperative supraventricular tachycardias in patients with univentricular heart: a European multicenter study

    NARCIS (Netherlands)

    de Groot, Natasja M. S.; Lukac, Peter; Blom, Nico A.; van Kuijk, Jan Peter; Pedersen, Anders K.; Hansen, Peter S.; Delacretaz, Etienne; Schalij, Martin J.

    2009-01-01

    BACKGROUND: Catheter ablation has evolved as a possible curative treatment modality for supraventricular tachycardias (SVT) in patients with univentricular heart. However, the long-term outcome of ablation procedures is unknown. We evaluated the procedural and long-term outcome of ablative therapy

  1. A coronary heart disease risk model for predicting the effect of potent antiretroviral therapy in HIV-1 infected men

    DEFF Research Database (Denmark)

    May, Margaret; Sterne, Jonathan A C; Shipley, Martin

    2007-01-01

    Many HIV-infected patients on highly active antiretroviral therapy (HAART) experience metabolic complications including dyslipidaemia and insulin resistance, which may increase their coronary heart disease (CHD) risk. We developed a prognostic model for CHD tailored to the changes in risk factors...

  2. SCA1+ Cells from the Heart Possess a Molecular Circadian Clock and Display Circadian Oscillations in Cellular Functions

    Directory of Open Access Journals (Sweden)

    Bastiaan C. Du Pré

    2017-09-01

    Full Text Available Stem cell antigen 1-positive (SCA1+ cells (SPCs have been investigated in cell-based cardiac repair and pharmacological research, although improved cardiac function after injection has been variable and the mode of action remains unclear. Circadian (24-hr rhythms are biorhythms regulated by molecular clocks that play an important role in (pathophysiology. Here, we describe (1 the presence of a molecular circadian clock in SPCs and (2 circadian rhythmicity in SPC function. We isolated SPCs from human fetal heart and found that these cells possess a molecular clock based on typical oscillations in core clock components BMAL1 and CRY1. Functional analyses revealed that circadian rhythmicity also governs SPC proliferation, stress tolerance, and growth factor release, with large differences between peaks and troughs. We conclude that SPCs contain a circadian molecular clock that controls crucial cellular functions. Taking circadian rhythms into account may improve reproducibility and outcome of research and therapies using SPCs.

  3. Nanotechnology and stem cell therapy for cardiovascular diseases: potential applications.

    Science.gov (United States)

    La Francesca, Saverio

    2012-01-01

    The use of stem cell therapy for the treatment of cardiovascular diseases has generated significant interest in recent years. Limitations to the clinical application of this therapy center on issues of stem cell delivery, engraftment, and fate. Nanotechnology-based cell labeling and imaging techniques facilitate stem cell tracking and engraftment studies. Nanotechnology also brings exciting new opportunities to translational stem cell research as it enables the controlled engineering of nanoparticles and nanomaterials that can properly relate to the physical scale of cell-cell and cell-niche interactions. This review summarizes the most relevant potential applications of nanoscale technologies to the field of stem cell therapy for the treatment of cardiovascular diseases.

  4. Delivery Strategies for Stem Cell-Based Therapy

    Directory of Open Access Journals (Sweden)

    Jason P. Glotzbach

    2012-01-01

    Full Text Available Before stem cell-based therapies can become a clinical reality, technologies for cell delivery must be developed that can control differentiation and pluripotency, maintain a hospitable environment for cell survival and function, and provide a structural framework for regenerative healing of the target tissue. Insights gained from developmental and stem cell biology should guide the design of devices and techniques to facilitate stem cell-based therapies. Several strategies have been developed for surgical delivery of stem cells, including synthetic and biologic matrices for cell seeding, complex biochemical delivery devices for maintenance and modulation of stem cell properties, and smart constructs with the ability to adapt to the dynamic in vivo environment after implantation. In aggregate, surgical delivery of complex stem cell-seeded constructs has the potential to revolutionize surgical therapies for a wide range of diseases in order to provide a more regenerative platform for tissue and organ healing.

  5. Stem cell therapy for glaucoma: science or snake oil?

    Science.gov (United States)

    Sun, Yi; Williams, Alice; Waisbourd, Michael; Iacovitti, Lorraine; Katz, L Jay

    2015-01-01

    In recent years there has been substantial progress in developing stem cell treatments for glaucoma. As a downstream approach that targets the underlying susceptibility of retinal ganglion and trabecular meshwork cells, stem cell therapy has the potential to both replace lost, and protect damaged, cells by secreting neurotrophic factors. A variety of sources, including embryonic cells, adult cells derived from the central nervous system, and induced pluripotent stem cells show promise as therapeutic approaches. Even though safety concerns and ethical controversies have limited clinical implementation, some institutions have already commercialized stem cell therapy and are using direct-to-consumer advertising to attract patients with glaucoma. We review the progress of stem cell therapy and its current commercial availability. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Eugene [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Corbett, James R. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Moran, Jean M. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Griffith, Kent A. [Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (United States); Marsh, Robin B.; Feng, Mary; Jagsi, Reshma; Kessler, Marc L. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Ficaro, Edward C. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Pierce, Lori J., E-mail: ljpierce@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

    2013-03-15

    Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses to the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.

  7. Low-Level Laser Therapy to the Bone Marrow Reduces Scarring and Improves Heart Function Post-Acute Myocardial Infarction in the Pig.

    Science.gov (United States)

    Blatt, Alex; Elbaz-Greener, Gabby A; Tuby, Hana; Maltz, Lidya; Siman-Tov, Yariv; Ben-Aharon, Gad; Copel, Laurian; Eisenberg, Itzhak; Efrati, Shai; Jonas, Michael; Vered, Zvi; Tal, Sigal; Goitein, Orly; Oron, Uri

    2016-11-01

    Cell therapy for myocardial repair is one of the most intensely investigated strategies for treating acute myocardial infarction (MI). The aim of the present study was to determine whether low-level laser therapy (LLLT) application to stem cells in the bone marrow (BM) could affect the infarcted porcine heart and reduce scarring following MI. MI was induced in farm pigs by percutaneous balloon inflation in the left coronary artery for 90 min. Laser was applied to the tibia and iliac bones 30 min, and 2 and 7 days post-induction of MI. Pigs were euthanized 90 days post-MI. The extent of scarring was analyzed by histology and MRI, and heart function was analyzed by echocardiography. The number of c-kit+ cells (stem cells) in the circulating blood of the laser-treated (LT) pigs was 2.62- and 2.4-fold higher than in the non-laser-treated (NLT) pigs 24 and 48 h post-MI, respectively. The infarct size [% of scar tissue out of the left ventricle (LV) volume as measured from histology] in the LT pigs was 3.2 ± 0.82%, significantly lower, 68% (p pigs. The mean density of small blood vessels in the infarcted area was significantly higher [6.5-fold (p pigs than in the NLT ones. Echocardiography (ECHO) analysis for heart function revealed the left ventricular ejection fraction in the LT pigs to be significantly higher than in the NLT ones. LLLT application to BM in the porcine model for MI caused a significant reduction in scarring, enhanced angiogenesis and functional improvement both in the acute and long term phase post-MI.

  8. Identification of genetic markers for treatment success in heart failure patients: insight from cardiac resynchronization therapy.

    Science.gov (United States)

    Schmitz, Boris; De Maria, Renata; Gatsios, Dimitris; Chrysanthakopoulou, Theodora; Landolina, Maurizio; Gasparini, Maurizio; Campolo, Jonica; Parolini, Marina; Sanzo, Antonio; Galimberti, Paola; Bianchi, Michele; Lenders, Malte; Brand, Eva; Parodi, Oberdan; Lunati, Maurizio; Brand, Stefan-Martin

    2014-12-01

    Cardiac resynchronization therapy (CRT) can improve ventricular size, shape, and mass and reduce mitral regurgitation by reverse remodeling of the failing ventricle. About 30% of patients do not respond to this therapy for unknown reasons. In this study, we aimed at the identification and classification of CRT responder by the use of genetic variants and clinical parameters. Of 1421 CRT patients, 207 subjects were consecutively selected, and CRT responder and nonresponder were matched for their baseline parameters before CRT. Treatment success of CRT was defined as a decrease in left ventricular end-systolic volume >15% at follow-up echocardiography compared with left ventricular end-systolic volume at baseline. All other changes classified the patient as CRT nonresponder. A genetic association study was performed, which identified 4 genetic variants to be associated with the CRT responder phenotype at the allelic (Pheart failure patients in CRT responder and nonresponder status using clinical and genetic parameters. Our analysis included information on alleles and genotypes of 4 genetic loci, rs3766031 (ATPIB1), rs5443 (GNB3), rs5522 (NR3C2), and rs7325635 (TNFSF11), pathophysiologically associated with remodeling of the failing ventricle. © 2014 American Heart Association, Inc.

  9. Ranolazine improves autonomic balance in heart failure when added to guideline-driven therapy

    Directory of Open Access Journals (Sweden)

    Gary L. Murray

    2014-12-01

    Full Text Available Background The effect of ranolazine (RAN on cardiac autonomic balance in congestive heart failure (CHF was studied. Methods Fifty-four CHF patients were randomized to (1 open-label RAN (RANCHF added to usual therapy vs. (2 usual therapy (NORANCHF. Parasympathetic and sympathetic (P&S measurements were taken at baseline and at 12 months. Results A total of 16/27 (59% patients in both groups had initially abnormal P&S measures, including high sympathovagal balance (SB, cardiovascular autonomic neuropathy (CAN or both. High SB normalized in 10/12 (83% RANCHF patients vs. 2/11 (18% NORANCHF patients. SB became high in 5/11 (45% NORANCHF vs. 1/11 (9% RANCHF patients. CAN improved in 4/6 (67% RANCHF patients vs. 5/7 (45% NORANCHF patients. CAN developed in 1/11 (9% RANCHF vs. 4/11 (36% NORANCHF patients. Since improved P&S in RANCHF patients seemed independent of improved brain natriuretic peptide and impedance cardiography (BioZ measurements, 5 day RAN was given to 30 subjects without CHF but with high SB or CAN. P&S improved in 90% of these subjects. Conclusions RAN improves unfavorable P&S activity in CHF possibly by a direct effect upon autonomic sodium channels.

  10. Heart failure in patients with kidney disease and iron deficiency; the role of iron therapy.

    Science.gov (United States)

    Cases Amenós, Aleix; Ojeda López, Raquel; Portolés Pérez, José María

    Chronic kidney disease and anaemia are common in heart failure (HF) and are associated with a worse prognosis in these patients. Iron deficiency is also common in patients with HF and increases the risk of morbidity and mortality, regardless of the presence or absence of anaemia. While the treatment of anaemia with erythropoiesis-stimulating agents in patients with HF have failed to show a benefit in terms of morbidity and mortality, treatment with IV iron in patients with HF and reduced ejection fraction and iron deficiency is associated with clinical improvement. In a posthoc analysis of a clinical trial, iron therapy improved kidney function in patients with HF and iron deficiency. In fact, the European Society of Cardiology's recent clinical guidelines on HF suggest that in symptomatic patients with reduced ejection fraction and iron deficiency, treatment with IV ferric carboxymaltose should be considered to improve symptoms, the ability to exercise and quality of life. Iron plays a key role in oxygen storage (myoglobin) and in energy metabolism, and there are pathophysiological bases that explain the beneficial effect of IV iron therapy in patients with HF. All these aspects are reviewed in this article. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  11. Heart rate Variability and Efficiency Assessment of Graves' Disease Radioiodine Therapy

    Directory of Open Access Journals (Sweden)

    M L Budkina

    2009-03-01

    Full Text Available Time of the transformation to the euthyroid condition after radioiodine therapy of Grave’s disease is individual and deviates from weeks to months, what requires frequent hormones control. The aim of this study was the assessment of possibility to use HRV parameters in dynamic control after the radioiodine therapy. 77 patients were examined with 114 fT4 measurement and HRV parameters recording (before radioiodine administration and in 1, 3, 6, 12 months after. From HRV parameters two were chosen as characterizing the closest correlation with fT4 and relatively independent from each other. The whole sample was divided into the teaching set (86 measurements and the test set (28 measurements. The decision rule was found by support vector machine in the teaching set asf(HR,SDNN = 0.995 lg(HR – 0.104 lg(SDNN – 1.703, where f is the indicator of the thyroid gland function, HR – heart rate during 5-minute ECG recording; SDNN – standard deviation of RR intervals; 0.995 , 0.104 and 1.703 – correcting coefficients. If f > 0, the thyrotoxicosis takes place in a patient. If f < 0 – there is no thyrotoxicosis. The analysis of diagnostic method precision in testing set gave the following results: diagnostic sensitivity was 71%, the diagnostic specificity 79%. This method can predict thyrotoxicosis elimination or relapse with high possibility. Its use can optimize thyroid function control and refuse from fixed time hormone measurement.

  12. Improvement of Circadian Rhythm of Heart Rate Variability by Eurythmy Therapy Training

    Directory of Open Access Journals (Sweden)

    Georg Seifert

    2013-01-01

    Full Text Available Background. Impairment of circadian rhythm is associated with various clinical problems. It not only has a negative impact on quality of life but can also be associated with a significantly poorer prognosis. Eurythmy therapy (EYT is an anthroposophic movement therapy aimed at reducing fatigue symptoms and stress levels. Objective. This analysis of healthy subjects was conducted to examine whether the improvement in fatigue symptoms was accompanied by improvements in the circadian rhythm of heart rate variability (HRV. Design. Twenty-three women performed 10 hours of EYT over six weeks. Electrocardiograms (ECGs were recorded before and after the EYT trial. HRV was quantified by parameters of the frequency and time domains and the nonlinear parameters of symbolic dynamics. Results. The day-night contrast with predominance of vagal activity at night becomes more pronounced after the EYT training, and with decreased Ultralow and very low frequencies, the HRV shows evidence of calmer sleep. During the night, the complexity of the HRV is significantly increased indicated by nonlinear parameters. Conclusion. The analysis of the circadian patterns of cardiophysiological parameters before and after EYT shows significant improvements in HRV in terms of greater day-night contrast caused by an increase of vagal activity and calmer and more complex HRV patterns during sleep.

  13. Nocturnal heart rate variability in patients treated with cognitive-behavioral therapy for insomnia.

    Science.gov (United States)

    Jarrin, Denise C; Chen, Ivy Y; Ivers, Hans; Lamy, Manon; Vallières, Annie; Morin, Charles M

    2016-06-01

    Insomnia and reduced heart rate variability (HRV) increase the risk of cardiovascular disease and its precursors; thus, it is important to evaluate whether treatment for insomnia provides cardiovascular safeguards. The present study aimed to evaluate potential cardiovascular benefits of cognitive behavioral therapy for insomnia (CBT-I). The present study included 65 patients treated for chronic insomnia (M = 51.8 years, SD = 10.0; 66.2% female) at a university hospital. Patients received CBT-I over a 6-week period, and change scores from pre- to posttreatment derived from the Insomnia Severity Index, sleep diary, and polysomnography (PSG) were used as indices of sleep improvement. HRV variables (i.e., low frequency [LF], high frequency [HF], and the ratio of low to high frequency [LF:HF ratio]) were derived for Stage 2 (S2) and rapid-eye movement (REM) sleep at pre- and posttreatment. High HF (i.e., parasympathetic activity) and/or low LF:HF ratio (i.e., sympathovagal balance) were used as indices of HRV improvement. Following therapy, sleep improvements, particularly for sleep onset latency, were related with reduced HF in S2 (r = .30, p treatment might play a role in physiological changes associated with cardiovascular anomalies. Future research is needed to examine the long-term impact of treatment as a preventative tool against insomnia-related morbidity. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  14. HeartSmart® for routine optimization of blood flow and facilitation of early goal-directed therapy

    Directory of Open Access Journals (Sweden)

    Kenneth Warring-Davies

    2010-08-01

    PAC thermodilution. HeartSmart® removes many of the technical barriers that prevent the routine adoption and practice of early goal-directed therapy, and represents a simple, reliable method of estimating CI and other hemodynamic variables at the bedside or in departments other than the Intensive Care Unit.Keywords: cardiac index, early goal-directed therapy, HeartSmart®, cardiodynamics, blood flow

  15. Concurrent Isolation of 3 Distinct Cardiac Stem Cell Populations From a Single Human Heart Biopsy.

    Science.gov (United States)

    Monsanto, Megan M; White, Kevin S; Kim, Taeyong; Wang, Bingyan J; Fisher, Kristina; Ilves, Kelli; Khalafalla, Farid G; Casillas, Alexandria; Broughton, Kathleen; Mohsin, Sadia; Dembitsky, Walter P; Sussman, Mark A

    2017-07-07

    The relative actions and synergism between distinct myocardial-derived stem cell populations remain obscure. Ongoing debates on optimal cell population(s) for treatment of heart failure prompted implementation of a protocol for isolation of multiple stem cell populations from a single myocardial tissue sample to develop new insights for achieving myocardial regeneration. Establish a robust cardiac stem cell isolation and culture protocol to consistently generate 3 distinct stem cell populations from a single human heart biopsy. Isolation of 3 endogenous cardiac stem cell populations was performed from human heart samples routinely discarded during implantation of a left ventricular assist device. Tissue explants were mechanically minced into 1 mm3 pieces to minimize time exposure to collagenase digestion and preserve cell viability. Centrifugation removes large cardiomyocytes and tissue debris producing a single cell suspension that is sorted using magnetic-activated cell sorting technology. Initial sorting is based on tyrosine-protein kinase Kit (c-Kit) expression that enriches for 2 c-Kit+ cell populations yielding a mixture of cardiac progenitor cells and endothelial progenitor cells. Flowthrough c-Kit- mesenchymal stem cells are positively selected by surface expression of markers CD90 and CD105. After 1 week of culture, the c-Kit+ population is further enriched by selection for a CD133+ endothelial progenitor cell population. Persistence of respective cell surface markers in vitro is confirmed both by flow cytometry and immunocytochemistry. Three distinct cardiac cell populations with individualized phenotypic properties consistent with cardiac progenitor cells, endothelial progenitor cells, and mesenchymal stem cells can be successfully concurrently isolated and expanded from a single tissue sample derived from human heart failure patients. © 2017 American Heart Association, Inc.

  16. Cell-based therapy technology classifications and translational challenges.

    Science.gov (United States)

    Mount, Natalie M; Ward, Stephen J; Kefalas, Panos; Hyllner, Johan

    2015-10-19

    Cell therapies offer the promise of treating and altering the course of diseases which cannot be addressed adequately by existing pharmaceuticals. Cell therapies are a diverse group across cell types and therapeutic indications and have been an active area of research for many years but are now strongly emerging through translation and towards successful commercial development and patient access. In this article, we present a description of a classification of cell therapies on the basis of their underlying technologies rather than the more commonly used classification by cell type because the regulatory path and manufacturing solutions are often similar within a technology area due to the nature of the methods used. We analyse the progress of new cell therapies towards clinical translation, examine how they are addressing the clinical, regulatory, manufacturing and reimbursement requirements, describe some of the remaining challenges and provide perspectives on how the field may progress for the future. © 2015 The Authors.

  17. Impact of statin therapy on patients with coronary heart disease and aortic aneurysm or dissection.

    Science.gov (United States)

    Tazaki, Junichi; Morimoto, Takeshi; Sakata, Ryuzo; Okabayashi, Hitoshi; Yamazaki, Fumio; Nishiwaki, Noboru; Mitsudo, Kazuaki; Kimura, Takeshi

    2014-09-01

    The impact of statin therapy on cardiovascular outcome in coronary artery disease (CAD) patients with aortic aneurysm or dissection (AD) is still unclear. The aim of this study was to elucidate the effect of statins at discharge to improve outcomes in CAD patients with AD. Among 14,834 consecutive patients who underwent first coronary revascularization in the CREDO-Kyoto PCI/CABG registry, we identified 699 patients (4.7%) with AD. The primary outcome measure was defined as a composite of all-cause death, myocardial infarction, and stroke. The effect of statin therapy was assessed by a Cox proportional hazards model incorporating clinically relevant factors. The risk for the primary outcome measure was significantly higher in patients with AD (adjusted hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.23-1.66; P aneurysm repair, and only 274 patients (39%) were treated with statins at discharge. Patients treated with statins were younger, had higher body mass index, and were more often treated with percutaneous coronary intervention. Heart failure, anemia, and hemodialysis were more prevalent in patients treated without statins. In patients without AD, 7014 patients (50%) were treated with statins. Patients treated with statins were younger and had higher body mass index, and more patients were treated for CAD due to myocardial infarction. Heart failure, prior stroke, hemodialysis, anemia, and malignant disease were more prevalent in patients treated without statins. The use of statins was associated with lower risk for the primary outcome measure in patients with AD (adjusted HR, 0.71; 95% CI, 0.51-0.99; P = .045) as well as in patients without AD (adjusted HR, 0.79; 95% CI, 0.73-0.85; P < .0001). The effect size of statin use was similar between the patients with AD and those without AD (P interaction = .69). CAD patients with AD had significantly higher long-term risk for cardiovascular events. Statin therapy was associated with lower risk for

  18. Effect of a combined anti-thrombotic therapy of thrombosis on prosthetic heart valves.

    Science.gov (United States)

    Wei, Wei; Dong, Taiming; Zheng, Zhichao; Huang, Shuping

    2015-03-01

    To evaluate the curative effects and risks of a medical therapy with combined anti-thrombotic agents for thrombosis on prosthetic heart valves. Twenty-two patients who suffered from thrombosis on prosthetic valves with stable hemodynamics were divided into the inpatient group and the outpatient group. Thrombosis on the valves were demonstrated by transesophageal echocardiographies (TEE). A combined anti-thrombotic therapy with clopidogrel and warfarin were prescribed for all the patients during the whole treatment. Low molecular weight heparin (LMWH) was given twice daily during the first 5 days for the inpatients. The patients accepted regular follow-ups for observation of the functions of prosthetic valves, changes of thrombi, coagulation status and general clinical status. There were 5 men and 17 women. Thirteen patients suffered from thrombosis on the mechanical mitral valves (MVs), five on the mechanical tricuspid valves (TVs), one on the mechanical aortic valve and tricuspid bio-prosthetic valve, one on the mechanical aortic valve, one on the mitral bio-prosthetic valve, and one on the tricuspid bio-prosthetic valve. After an average of 36.4±23.1 days' observation, 16 (73%) patients' valvular function recovered normal without TTE detectable thrombi, 6 (27%) patients' valvular function remained abnormal including three patients without TTE detectable thrombi during follow-ups. No significant differences of thrombi changes and period of thrombi disappearance were observed between the inpatient group and the outpatient group. For patients with mitral thrombosis, sizes of the left atriums (LAs) decreased an average of 4.1 mm after treatment (95% CI, 1.2-6.9 mm). No significant changes of other chambers and left ventricular ejection fractions (LVEF) were observed. For patients with tricuspid thrombosis, LVEF improved an average of 10.5% after treatment (95% CI, 0.1-17.9%). No significant changes of chambers were observed. None experienced major bleedings except

  19. Assessment of DNA synthesis in Islet-1{sup +} cells in the adult murine heart

    Energy Technology Data Exchange (ETDEWEB)

    Weinberger, Florian, E-mail: f.weinberger@uke.de; Mehrkens, Dennis, E-mail: dennis.mehrkens@uk-koeln.de; Starbatty, Jutta, E-mail: starbatty@uke.uni-hamburg.de; Nicol, Philipp, E-mail: Philipp.Nicol@gmx.de; Eschenhagen, Thomas, E-mail: t.eschenhagen@uke.de

    2015-01-02

    Highlights: • Islet-1 was expressed in the adult heart. • Islet-1-positive cells did not proliferate in the adult heart. • Sinoatrial node cells did not proliferate in the adult heart. - Abstract: Rationale: Islet-1 positive (Islet-1{sup +}) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1{sup +} cells retain proliferative activity and may therefore play a role in regenerating specialized regions in the heart. Methods and results: DNA synthesis was analyzed by the incorporation of tritiated thymidine ({sup 3}H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of {sup 3}H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1{sup +} cells. Whereas Islet{sup −} non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed. Conclusions: Islet-1{sup +} cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes.

  20. Towards a myocardial contraction force reconstruction technique for heart disease assessment and therapy planning

    Science.gov (United States)

    Haddad, Seyyed M. H.; Drangova, Maria; White, James A.; Samani, Abbas

    2014-03-01

    Cardiac ischemic injuries can be classified into two main categories: reversible and irreversible. Treatment of reversible damages is possible through revascularization therapies. Clinically, it is quite vital to determine the reversibility of ischemic injuries and local efficiency using accurate diagnostics techniques. For this purpose, a number of imaging techniques have been developed. To our knowledge, while some of these techniques are capable of assessing tissue viability which is believed to be correlated with ischemic injuries reversibility, none of them are capable of providing information about local myocardial tissue efficiency. Note that this efficiency indicates the local tissue contribution to the overall (global) heart mechanical function which is characterized by parameters such as ejection fraction. While contraction force generation of the myocardium is a reliable and straightforward mechanical measure for the local myocardium functionality, it is also hypothesized that the level of damage reversibility expected from therapy is proportional to the intensity and distribution of these forces. As such this research involves developing a new imaging technique for cardiac contraction force quantification. This work is also geared towards another application, namely Cardiac Resynchronization Therapy (CRT), specifically for electrode leads configuration optimization. The latter has not been tackled through a systematic technique thus far. In the proposed method, contraction force reconstruction is accomplished by an inverse problem algorithm solved through an optimization framework which uses forward mechanical modelling of the myocardium iteratively to obtain the contraction forces field. As a result, the method requires a forward mechanical model of the myocardium which is computationally efficient and robust against divergence. Therefore, we developed such a model which considers all aspects of the myocardial mechanics including hyperelasticity

  1. Effect of CD4+ memory T cells on rejection response of ectopic heart transplantation in mice.

    Science.gov (United States)

    Zhao, Y; Shan, Z; Li, Q; Zhou, Y; Zeng, X; Fan, Q; Liao, C; Zhu, Y; Zhao, Y; Lu, X; Liu, J

    2011-06-01

    CD4(+) memory T cells mediate resistance of the body to infection by exotic pathogens. This study investigated the effects of alloreactive CD4(+) memory T cells on acute graft rejection responses toward ectopic hearts in the abdominal cavities of mice. BALB/C mice were used as recipients and C57BL/6 mice as donors. The animals in the CD4(+) memory T-cell group were infused with CD4(+) memory T cells, those in the other group were infused with nonsensitized CD4(+) T cells, and those in the control group received no CD4(+) T cells. Heart transplantation was performed at 3 weeks after the cell infusion with cyclosporine administered beginning 1 day before transplantation via intraperitoneal injection. The survival among the CD4(+) memory T-cell group was significantly shorter than that of the nonsensitized CD4(+) T-cell group or the control group (P .05; n = 10). On the 5th day after the transplantation of heart, the histologic grades of the nonsensitized CD4(+) T-cell and the blank control group were lower than those of the CD4(+) memory T-cell group. There was no significant difference in the histologic grades between the nonsensitized CD4(+) T-cell and control groups. The CD4(+) memory T cells that mediate acute rejection of allografted hearts are insensitive to cyclosporine. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Characteristic of c-Kit+ progenitor cells in explanted human hearts

    OpenAIRE

    Matuszczak, Sybilla; Czapla, Justyna; Jarosz-Biej, Magdalena; Wiśniewska, Ewa; Cichoń, Tomasz; Smolarczyk, Ryszard; Kobusińska, Magdalena; Gajda, Karolina; Wilczek, Piotr; Śliwka, Joanna; Zembala, Michał; Zembala, Marian; Szala, Stanisław

    2014-01-01

    According to literature data, self-renewing, multipotent, and clonogenic cardiac c-Kit+ progenitor cells occur within human myocardium. The aim of this study was to isolate and characterize c-Kit+ progenitor cells from explanted human hearts. Experimental material was obtained from 19 adult and 7 pediatric patients. Successful isolation and culture was achieved for 95 samples (84.1 %) derived from five different regions of the heart: right and left ventricles, atrium, intraventricular septum,...

  3. Cell therapy in myocardial infarction: emphasis on the role of MRI

    Energy Technology Data Exchange (ETDEWEB)

    Ye, Yuxiang; Bogaert, Jan [University Hospital K.U.L., Department of Radiology, Leuven (Belgium)

    2008-03-15

    Despite tremendous progress in myocardial infarct (MI) treatment, mortality rates remain substantial. Permanent loss of cardiomyocytes after ischemic injury, results in irreversible loss of myocardial contractility, reduction in ventricular performance, and may initiate the development of dilated heart failure. The discovery that pluripotent progenitor cells bear the capacity to differentiate to mature cardiac cells raised the hope of cell-based regenerative medicine. Engraftment of stem cells in the damaged myocardium, repair and functional improvement appeared suddenly a nearby reality. Promising results in animal models, and preliminary studies reporting the feasibility and safety of adult stem cell therapy in MI patients led to the first double-blinded randomized, placebo-controlled trials. The initial great enthusiasm for this paradigm shift in MI treatment has been tempered by the mainly negative or modestly positive study findings. Before new, larger clinical trials can be initiated, a number of critical questions and issues need to be considered starting with a scrutinized analysis of currently available data to extending our knowledge of the mechanism of scarless myocardial regeneration. Cardiac cell therapy necessitates a multidisciplinary approach, whereby imaging, in particular MRI, and the input of the imaging specialist is crucial to the success of cardiac cell regenerative medicine. MRI is an appealing technique for cell trafficking depicting engraftment, differentiation and survival. Endomyocardial cell administration can be achieved safely with MR fluoroscopy and MRI is without any doubt the most accurate and reproducible technique to measure study end-points. (orig.)

  4. Molecular Imaging in Stem Cell Therapy for Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Fahuan Song

    2014-01-01

    Full Text Available Spinal cord injury (SCI is a serious disease of the center nervous system (CNS. It is a devastating injury with sudden loss of motor, sensory, and autonomic function distal to the level of trauma and produces great personal and societal costs. Currently, there are no remarkable effective therapies for the treatment of SCI. Compared to traditional treatment methods, stem cell transplantation therapy holds potential for repair and functional plasticity after SCI. However, the mechanism of stem cell therapy for SCI remains largely unknown and obscure partly due to the lack of efficient stem cell trafficking methods. Molecular imaging technology including positron emission tomography (PET, magnetic resonance imaging (MRI, optical imaging (i.e., bioluminescence imaging (BLI gives the hope to complete the knowledge concerning basic stem cell biology survival, migration, differentiation, and integration in real time when transplanted into damaged spinal cord. In this paper, we mainly review the molecular imaging technology in stem cell therapy for SCI.

  5. Hot flushes, coronary heart disease, and hormone therapy in postmenopausal women.

    Science.gov (United States)

    Huang, Alison J; Sawaya, George F; Vittinghoff, Eric; Lin, Feng; Grady, Deborah

    2009-01-01

    The aim of this study was to examine interactions between hot flushes, estrogen plus progestogen therapy (EPT), and coronary heart disease (CHD) events in postmenopausal women with CHD. We analyzed data from the Heart and Estrogen/Progestin Replacement Study, a randomized, placebo-controlled trial of 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate in 2,763 postmenopausal women with CHD. Hot flushes were assessed at baseline using self-administered questionnaires; women reporting bothersome hot flushes "some" to "all" of the time were considered to have clinically significant flushing. Cox regression models were used to examine the effect of EPT on risk of CHD events among women with and without significant flushing at baseline. The mean age of participants was 66.7 +/- 6.8 years, and 89% (n = 2,448) were white. Sixteen percent (n = 434) of participants reported clinically significant hot flushes at baseline. Among women with baseline flushing, EPT increased risk of CHD events nine-fold in the first year compared with placebo (hazard ratio = 9.01; 95% CI, 1.15-70.35); among women without baseline flushing, treatment did not significantly affect CHD event risk in the first year (hazard ratio = 1.32; 95% CI, 0.86-2.03; P = 0.07 for interaction of hot flushes with treatment). The trend toward differential effects of EPT on risk for CHD among women with and without baseline flushing did not persist after the first year of treatment. Among older postmenopausal women with CHD, EPT may increase risk of CHD events substantially in the first year of treatment among women with clinically significant hot flushes but not among those without hot flushes.

  6. Cell therapy for spinal cord injury informed by electromagnetic waves.

    Science.gov (United States)

    Finnegan, Jack; Ye, Hui

    2016-10-01

    Spinal cord injury devastates the CNS, besetting patients with symptoms including but not limited to: paralysis, autonomic nervous dysfunction, pain disorders and depression. Despite the identification of several molecular and genetic factors, a reliable regenerative therapy has yet to be produced for this terminal disease. Perhaps the missing piece of this puzzle will be discovered within endogenous electrotactic cellular behaviors. Neurons and stem cells both show mediated responses (growth rate, migration, differentiation) to electromagnetic waves, including direct current electric fields. This review analyzes the pathophysiology of spinal cord injury, the rationale for regenerative cell therapy and the evidence for directing cell therapy via electromagnetic waves shown by in vitro experiments.

  7. Electrocardiographic Markers of Appropriate Implantable Cardioverter-Defibrillator Therapy in Young People with Congenital Heart Diseases.

    Science.gov (United States)

    Benítez Ramos, Dunia Bárbara; Cabrera Ortega, Michel; Castro Hevia, Jesús; Dorantes Sánchez, Margarita; Alemán Fernández, Ailema Amelia; Castañeda Chirino, Osmin; Cruz Cardentey, Marlenis; Martínez López, Frank; Falcón Rodríguez, Roylan

    2017-12-01

    Implantable cardioverter-defibrillators (ICDs) are increasingly utilized in patients with congenital heart disease (CHD). Prediction of the occurrence of shocks is important if improved patient selection is desired. The electrocardiogram (ECG) has been the first-line tool predicting the risk of sudden death, but data in CHD patients are lacking. We aim to evaluate the predictive value of electrocardiographic markers of appropriate therapy of ICD in young people with CHD. We conducted a prospective, longitudinal study, in twenty-six CHD patients (mean age 24.7 ± 5.3 years) who underwent first ICD implantation. Forty-two age- and diagnosis-matched controls were recruited. Twelve-lead ECG and 24 h Holter analysis were performed during a mean follow-up of 38.9 months. Data included heart rate, heart rate variability, QRS duration (QRSd), QTc interval and its dispersion, Tpeak-Tend (Tp-Te) interval and its dispersion, presence of fragmented QRS (fQRS), T wave alternans, atrial arrhythmias, and non-sustained ventricular tachycardia. Implant indication was primary prevention in ten cases (38.5%) and secondary prevention in 16 (61.5%). Overall, 17 subjects (65.3%) received at least one appropriate and effective ICD discharge. fQRS was present in 64.7% of cases with ICD therapy compared with patients without events or controls (p < 0.0001). Tp-e and Tp-e dispersion were significantly prolonged in patients with recurrences (113.5 and 37.2 ms) versus patients without ICD discharge (89.6 and 24.1 ms) or controls (72.4 and 19.3 ms) (p < 0.0001 and p < 0.0001, respectively). On univariate Cox regression analysis QRSd (hazard ratio: 1.19 per ms, p = 0.003), QTc dispersion (hazard ratio: 1.57 per ms, p = 0.002), fQRS (hazard ratio: 3.58 p < 0.0001), Tp-e (hazard ratio: 2.27 per ms, p < 0.0001), and Tp-e dispersion (hazard ratio: 4.15 per ms, p < 0.0001), emerged as strong predictors of outcome. On multivariate Cox analysis fQRS, Tp-e and Tp-e dispersion

  8. Targeting therapy-resistant cancer stem cells by hyperthermia

    DEFF Research Database (Denmark)

    Oei, A L; Vriend, L E M; Krawczyk, P M

    2017-01-01

    Eradication of all malignant cells is the ultimate but challenging goal of anti-cancer treatment; most traditional clinically-available approaches fail because there are cells in a tumour that either escape therapy or become therapy-resistant. A subpopulation of cancer cells, the cancer stem cells...... are limited. Here, we argue that hyperthermia - a therapeutic approach based on local heating of a tumour - is potentially beneficial for targeting CSCs in solid tumours. First, hyperthermia has been described to target cells in hypoxic and nutrient-deprived tumour areas where CSCs reside and ionising...

  9. Stem cell therapies for treating osteoarthritis: prescient or premature?

    Science.gov (United States)

    Whitworth, Deanne J; Banks, Tania A

    2014-12-01

    There has been unprecedented interest in recent years in the use of stem cells as therapy for an array of diseases in companion animals. Stem cells have already been deployed therapeutically in a number of clinical settings, in particular the use of mesenchymal stem cells to treat osteoarthritis in horses and dogs. However, an assessment of the scientific literature highlights a marked disparity between the purported benefits of stem cell therapies and their proven abilities as defined by rigorously controlled scientific studies. Although preliminary data generated from clinical trials in human patients are encouraging, therapies currently available to treat animals are supported by very limited clinical evidence, and the commercialisation of these treatments may be premature. This review introduces the three main types of stem cells relevant to veterinary applications, namely, embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells, and draws together research findings from in vitro and in vivo studies to give an overview of current stem cell therapies for the treatment of osteoarthritis in animals. Recent advances in tissue engineering, which is proposed as the future direction of stem cell-based therapy for osteoarthritis, are also discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Mesenchymal Stem Cells: Emerging Therapy for Duchenne Muscular Dystrophy

    OpenAIRE

    Markert, Chad; Atala, Anthony; Cann, Jennifer K.; Christ, George; Furth, Mark; Ambrosio, Fabrisia; Childers, Martin K.

    2009-01-01

    Multipotent cells that can give rise to bone, cartilage, fat, connective tissue, skeletal and cardiac muscle are termed mesenchymal stem cells (MSCs). These cells were first identified in the bone marrow, distinct from blood-forming stem cells. Based on the embryologic derivation, availability, and various pro-regenerative characteristics, research exploring their use in cell therapy shows great promise for patients with degenerative muscle diseases and a number of other conditions. In this r...

  11. Microencapsulation to reduce mechanical loss of microspheres: implications in myocardial cell therapy.

    Science.gov (United States)

    Al Kindi, Adil H; Asenjo, Juan Francisco; Ge, Yin; Chen, Guang Yong; Bhathena, Jasmine; Chiu, Ray C-J; Prakash, Satya; Shum-Tim, Dominique

    2011-02-01

    Previous regenerative studies have demonstrated massive cell losses after intramyocardial cellular delivery. Therefore, efforts at reducing mechanical losses may prove more successful in optimising cellular therapy. In this study, we hypothesized that escalating mesenchymal stem cells (MSCs) dose will not produce corresponding improvement in cardiac function due to washout of the small cells in microcirculation. Using microspheres similar in size to MSCs, that are encapsulated in alginate-poly-l-lysine-alginate (APA), we tested the hypothesis that size is an important factor in early losses. In experiment I, five groups of rats (n=9 each) underwent coronary ligation; group I had no treatment; the other groups received escalating 0.5 × 10(6), 1.5 × 10(6), 3 × 10(6) and 5 × 10(6) of MSCs each. Echocardiogram was performed at baseline, 2 days and 7 weeks after surgery. In experiment II, cell-sized microspheres (10 μm) were encapsulated in APA microcapsules. In group I (n=16), rats received bare microspheres, group II (n=16) microspheres within 200 μm microcapsules and in group III (n=16), microspheres within 400 μm microcapsules. After 20 min, hearts were quantified for the amount retained. Myocardial function did not improve further with escalating cell doses beyond an initial response at 1.5 × 10(6) cells. Encapsulated microspheres in 200 μm and 400 μm microcapsules demonstrated a fourfold increase in retention rate compared with 10 μm microspheres. We concluded that suboptimal functional improvement in this animal model starts at 1.5 × 10(6) cells and does not respond to escalating cell doses. Improving mechanical retention is possible by increasing the size of the injectate. Microencapsulation could be used to encapsulate donor cells and facilitate functional improvement in cellular heart failure therapy. Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

  12. Genetic Risk, Coronary Heart Disease Events, and the Clinical Benefit of Statin Therapy

    Science.gov (United States)

    Smith, JG; Chasman, DI; Caulfield, M; Devlin, JJ; Nordio, F; Hyde, C; Cannon, CP; Sacks, F; Poulter, N; Sever, P; Ridker, PM; Braunwald, E; Melander, O

    2015-01-01

    Background Genetic variants have been associated with the risk of coronary heart disease (CHD). We tested whether a composite of these variants could identify the risk of both incident as well as recurrent CHD events and distinguish individuals who derived greater clinical benefit from statin therapy. Methods A community-based cohort and four randomized controlled trials of both primary (JUPITER and ASCOT) and secondary (CARE and PROVE IT-TIMI 22) prevention with statin therapy totaling 48,421 individuals and 3,477 events were included in these analyses. We examined the association of a genetic risk score based on 27 genetic variants with incident or recurrent CHD, adjusting for established clinical predictors. We then investigated the relative and absolute risk reductions in CHD events with statin therapy stratified by genetic risk. Data from studies were combined using meta-analysis. Findings When individuals were divided into low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk categories, a significant gradient of risk for incident or recurrent CHD was demonstrated with the multivariable-adjusted HRs (95% CI) for CHD for the intermediate and high genetic risk categories vs. low genetic risk category being 1.32 (1.20-1.46, Prisk reduction across the low, intermediate, and high genetic risk categories (13%, 29%, and 48%, P=0.0277). Similarly, greater absolute risk reductions were seen in those individuals in higher genetic risk categories (P=0.0101), resulting in an approximate three-fold gradient in the number needed to treat (NNT) in the primary prevention trials. Specifically, in the primary prevention trials, the NNT to prevent one MACE over 10 years for the low, intermediate, and high GRS individuals was 66, 42, and 25 in JUPITER and 57, 47, and 20 in ASCOT. Interpretation A genetic risk score identified individuals at increased risk for both incident and recurrent CHD events. Individuals with the highest burden of genetic risk

  13. Carbohydrate Antigen-125-Guided Therapy in Acute Heart Failure: CHANCE-HF: A Randomized Study.

    Science.gov (United States)

    Núñez, Julio; Llàcer, Pau; Bertomeu-González, Vicente; Bosch, Maria José; Merlos, Pilar; García-Blas, Sergio; Montagud, Vicente; Bodí, Vicent; Bertomeu-Martínez, Vicente; Pedrosa, Valle; Mendizábal, Andrea; Cordero, Alberto; Gallego, Jorge; Palau, Patricia; Miñana, Gema; Santas, Enrique; Morell, Salvador; Llàcer, Angel; Chorro, Francisco J; Sanchis, Juan; Fácila, Lorenzo

    2016-11-01

    This study sought to evaluate the prognostic effect of carbohydrate antigen-125 (CA125)-guided therapy (CA125 strategy) versus standard of care (SOC) after a hospitalization for acute heart failure (AHF). CA125 has emerged as a surrogate of fluid overload and inflammatory status in AHF. After an episode of AHF admission, elevated values of this marker at baseline as well as its longitudinal profile relate to adverse outcomes, making it a potential tool for treatment guiding. In a prospective multicenter randomized trial, 380 patients discharged for AHF and high CA125 were randomly assigned to the CA125 strategy (n = 187) or SOC (n = 193). The aim in the CA125 strategy was to reduce CA125 to ≤35 U/ml by up or down diuretic dose, enforcing the use of statins, and tightening patient monitoring. The primary endpoint was 1-year composite of death or AHF readmission. Treatment strategies were compared as a time to first event and longitudinally. Patients allocated to the CA125 strategy were more frequently visited, and treated with ambulatory intravenous loop diuretics and statins. Likewise, doses of oral loop diuretics and aldosterone receptor blockers were more frequently modified. The CA125 strategy resulted in a significant reduction of the primary endpoint, whether evaluated as time to first event (66 events vs. 84 events; p = 0.017) or as recurrent events (85 events vs. 165 events; incidence rate ratio: 0.49; 95% confidence interval: 0.28 to 0.82; p = 0.008). The effect was driven by significantly reducing rehospitalizations but not mortality. The CA125 strategy was superior to the SOC in terms of reducing the risk of the composite of 1-year death or AHF readmission. This effect was mainly driven by significantly reducing the rate of rehospitalizations. (Carbohydrate Antigen-125-guided Therapy in Heart Failure [CHANCE-HF]; NCT02008110). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  14. Apoptosis and cancer stem cells : Implications for apoptosis targeted therapy

    NARCIS (Netherlands)

    Kruyt, Frank A. E.; Schuringa, Jan Jacob

    2010-01-01

    Evidence is accumulating showing that cancer stem cells or tumor-initiating cells are key drivers of tumor formation and progression. Successful therapy must therefore eliminate these cells, which is hampered by their high resistance to commonly used treatment modalities. Thus far, only a limited

  15. Recent advances in cell-based therapy for Parkinson disease

    DEFF Research Database (Denmark)

    Astradsson, Arnar; Cooper, Oliver; Vinuela, Angel

    2008-01-01

    In this review, the authors discuss recent advances in the field of cell therapy for Parkinson disease (PD). They compare and contrast recent clinical trials using fetal dopaminergic neurons. They attribute differences in cell preparation techniques, cell type specification, and immunosuppression...

  16. Stromal Vascular Fraction Transplantation as an Alternative Therapy for Ischemic Heart Failure: Anti-inflammatory Role

    Directory of Open Access Journals (Sweden)

    Lin Xue

    2011-03-01

    Full Text Available Abstract Background The aims of this study were: (1 to show the feasibility of using adipose-derived stromal vascular fraction (SVF as an alternative to bone marrow mono nuclear cell (BM-MNC for cell transplantation into chronic ischemic myocardium; and (2 to explore underlying mechanisms with focus on anti-inflammation role of engrafted SVF and BM-MNC post chronic myocardial infarction (MI against left ventricular (LV remodelling and cardiac dysfunction. Methods Four weeks after left anterior descending coronary artery ligation, 32 Male Lewis rats with moderate MI were divided into 3 groups. SVF group (n = 12 had SVF cell transplantation (6 × 106 cells. BM-MNC group (n = 12 received BM-MNCs (6 × 106 and the control (n = 10 had culture medium. At 4 weeks, after the final echocardiography, histological sections were stained with Styrus red and immunohistochemical staining was performed for α-smooth muscle actin, von Willebrand factor, CD3, CD8 and CD20. Results At 4 weeks, in SVF and BM-MNC groups, LV diastolic dimension and LV systolic dimension were smaller and fractional shortening was increased in echocardiography, compared to control group. Histology revealed highest vascular density, CD3+ and CD20+ cells in SVF transplanted group. SVF transplantation decreased myocardial mRNA expression of inflammatory cytokines TNF-α, IL-6, MMP-1, TIMP-1 and inhibited collagen deposition. Conclusions Transplantation of adipose derived SVF cells might be a useful therapeutic option for angiogenesis in chronic ischemic heart disease. Anti-inflammation role for SVF and BM transplantation might partly benefit for the cardioprotective effect for chronic ischemic myocardium.

  17. Artificial cell microencapsulated stem cells in regenerative medicine, tissue engineering and cell therapy.

    Science.gov (United States)

    Liu, Zun Chang; Chang, Thomas Ming Swi

    2010-01-01

    Adult stem cells, especially isolated from bone marrow, have been extensively investigated in recent years. Studies focus on their multiple plasticity oftransdifferentiating into various cell lineages and on their potential in cellular therapy in regenerative medicine. In many cases, there is the need for tissue engineering manipulation. Among the different approaches of stem cells tissue engineering, microencapsulation can immobilize stem cells to provide a favorable microenvironment for stem cells survival and functioning. Furthermore, microencapsulated stem cells are immunoisolated after transplantation. We show that one intraperitoneal injection of microencapsulated bone marrow stem cells can prolong the survival of liver failure rat models with 90% of the liver removed surgically. In addition to transdifferentiation, bone marrow stem cells can act as feeder cells. For example, when coencapsulated with hepatocytes, stem cells can increase the viability and function of the hepatocytes in vitro and in vivo.

  18. Artificial Cell Microencapsulated Stem Cells in Regenerative Medicine, Tissue Engineering and Cell Therapy

    Science.gov (United States)

    Liu, Zun Chang; Chang, Thomas Ming Swi

    2012-01-01

    Adult stem cells, especially isolated from bone marrow, have been extensively investigated in recent years. Studies focus on their multiple plasticity of transdifferentiating into various cell lineages and on their potential in cellular therapy in regenerative medicine. In many cases, there is the need for tissue engineering manipulation. Among the different approaches of stem cells tissue engineering, microencapsulation can immobilize stem cells to provide a favorable microenvironment for stem cells survival and functioning. Furthermore, microencapsulated stem cells are immunoisolated after transplantation. We show that one intraperitoneal injection of microencapsulated bone marrow stem cells can prolong the survival of liver failure rat models with 90% of the liver removed surgically. In addition to transdifferentiation, bone marrow stem cells can act as feeder cells. For example, when coencapsulated with hepatocytes, stem cells can increase the viability and function of the hepatocytes in vitro and in vivo. PMID:20384219

  19. Nano scaffolds and stem cell therapy in liver tissue engineering

    Science.gov (United States)

    Montaser, Laila M.; Fawzy, Sherin M.

    2015-08-01

    Tissue engineering and regenerative medicine have been constantly developing of late due to the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Although stem cells hold great potential for the treatment of many injuries and degenerative diseases, several obstacles must be overcome before their therapeutic application can be realized. These include the development of advanced techniques to understand and control functions of micro environmental signals and novel methods to track and guide transplanted stem cells. A major complication encountered with stem cell therapies has been the failure of injected cells to engraft to target tissues. The application of nanotechnology to stem cell biology would be able to address those challenges. Combinations of stem cell therapy and nanotechnology in tissue engineering and regenerative medicine have achieved significant advances. These combinations allow nanotechnology to engineer scaffolds with various features to control stem cell fate decisions. Fabrication of Nano fiber cell scaffolds onto which stem cells can adhere and spread, forming a niche-like microenvironment which can guide stem cells to proceed to heal damaged tissues. In this paper, current and emergent approach based on stem cells in the field of liver tissue engineering is presented for specific application. The combination of stem cells and tissue engineering opens new perspectives in tissue regeneration for stem cell therapy because of the potential to control stem cell behavior with the physical and chemical characteristics of the engineered scaffold environment.

  20. Metastasis in renal cell carcinoma: Biology and implications for therapy

    Directory of Open Access Journals (Sweden)

    Jun Gong

    2016-10-01

    Full Text Available Although multiple advances have been made in systemic therapy for renal cell carcinoma (RCC, metastatic RCC remains incurable. In the current review, we focus on the underlying biology of RCC and plausible mechanisms of metastasis. We further outline evolving strategies to combat metastasis through adjuvant therapy. Finally, we discuss clinical patterns of metastasis in RCC and how distinct systemic therapy approaches may be considered based on the anatomic location of metastasis.

  1. Progenitor Hematopoietic Cells Implantation Improves Functional Capacity of End Stage Coronary Artery Disease Patients with Advanced Heart Failure

    Directory of Open Access Journals (Sweden)

    Yoga Yuniadi

    2016-01-01

    Full Text Available Background. Proangiogenic Hematopoietic Cells (PHC which comprise diverse mixture of cell types are able to secrete proangiogenic factors and interesting candidate for cell therapy. The aim of this study was to seek for benefit in implantation of PHC on functional improvement in end stage coronary artery disease patients with advanced heart failure. Methods. Patients with symptomatic heart failure despite guideline directed medical therapy and LVEF less than 35% were included. Peripheral blood mononuclear cells were isolated, cultivated for 5 days, and then harvested. Flow cytometry and cell surface markers were used to characterize PHC. The PHC were delivered retrogradely via sinus coronarius. Echocardiography, myocardial perfusion, and clinical and functional data were analyzed up to 1-year observation. Results. Of 30 patients (56.4±7.40 yo preimplant NT proBNP level is 5124.5±4682.50 pmol/L. Harvested cells characterized with CD133, CD34, CD45, and KDR showed 0.87±0.41, 0.63±0.66, 99.00±2.60, and 3.22±3.79%, respectively. LVEF was improved (22±5.68 versus 26.8±7.93, p<0.001 during short and long term observation. Myocardial perfusion significantly improved 6 months after treatment. NYHA Class and six-minute walk test are improved during short term and long term follow-up. Conclusion. Expanded peripheral blood PHC implantation using retrograde delivery approach improved LV systolic function, myocardial perfusion, and functional capacity.

  2. Maternal hyperoxygenation: A potential therapy for congenital heart disease in the fetuses? A systematic review of the current literature.

    Science.gov (United States)

    Co-Vu, Jennifer; Lopez-Colon, Dalia; Vyas, Himesh V; Weiner, Natalie; DeGroff, Curt

    2017-12-01

    To assess efficacy, safety, outcomes, and intrauterine complications following maternal hyperoxygenation (MH) therapy in fetuses with congenital heart disease (CHD). A systematic review was performed following an electronic search of databases. Articles were published before January 1, 2017, in an English-language and non-English-language journals (with English translations), and included human fetuses and expectant mothers with a fetal diagnosis of CHD who received MH. Ninety-six articles were identified; 72 were excluded and 24 full-text articles were reviewed. Only 9 articles met inclusion criteria and were analyzed. A total of 270 fetuses underwent MH therapy: 169 had CHD, and 101 had normal heart anatomies. Seven studies used fetal echocardiography, while 2 studies used cardiac magnetic resonance imaging (CMR). The mean gestational age at therapy was 33.4 weeks (26-38 weeks). Majority of MH protocols used 100% FiO2 with non-rebreather face mask at 8 L of flow, achieving 60%-70% FiO2 , or maternal PaO2 goal of 250 mm Hg. No significant adverse events were reported. Four studies reported increased size of the hypoplastic cardiac structures after MH. Three studies utilized acute MH to risk stratify hypoplastic left heart syndrome fetuses. Two studies assessed acute MH in the setting of CMR. The current evidence for MH therapy suggests an increase in pulmonary blood flow, and venous return, ductal flow, and heart dimensions in fetuses. MH has potential as a diagnostic and therapeutic tool in fetuses with CHD. Further randomized controlled trials are needed to ascertain whether MH therapy provides improved outcomes on fetuses with certain types of CHD. © 2017, Wiley Periodicals, Inc.

  3. Stem Cell Based Gene Therapy in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Jae Heon Kim

    2014-01-01

    Full Text Available Current prostate cancer treatment, especially hormone refractory cancer, may create profound iatrogenic outcomes because of the adverse effects of cytotoxic agents. Suicide gene therapy has been investigated for the substitute modality for current chemotherapy because it enables the treatment targeting the cancer cells. However the classic suicide gene therapy has several profound side effects, including immune-compromised due to viral vector. Recently, stem cells have been regarded as a new upgraded cellular vehicle or vector because of its homing effects. Suicide gene therapy using genetically engineered mesenchymal stem cells or neural stem cells has the advantage of being safe, because prodrug administration not only eliminates tumor cells but consequently kills the more resistant therapeutic stem cells as well. The attractiveness of prodrug cancer gene therapy by stem cells targeted to tumors lies in activating the prodrug directly within the tumor mass, thus avoiding systemic toxicity. Therapeutic achievements using stem cells in prostate cancer include the cytosine deaminase/5-fluorocytosine prodrug system, herpes simplex virus thymidine kinase/ganciclovir, carboxyl esterase/CPT11, and interferon-beta. The aim of this study is to review the stem cell therapy in prostate cancer including its proven mechanisms and also limitations.

  4. Waon Therapy for Managing Chronic Heart Failure - Results From a Multicenter Prospective Randomized WAON-CHF Study.

    Science.gov (United States)

    Tei, Chuwa; Imamura, Teruhiko; Kinugawa, Koichiro; Inoue, Teruo; Masuyama, Tohru; Inoue, Hiroshi; Noike, Hirofumi; Muramatsu, Toshihiro; Takeishi, Yasuchika; Saku, Keijiro; Harada, Kazumasa; Daida, Hiroyuki; Kobayashi, Youichi; Hagiwara, Nobuhisa; Nagayama, Masatoshi; Momomura, Shinichi; Yonezawa, Kazuya; Ito, Hiroshi; Gojo, Satoshi; Akaishi, Makoto; Miyata, Masaaki; Ohishi, Mitsuru

    2016-01-01

    Waon therapy improves heart failure (HF) symptoms, but further evidence in patients with advanced HF remains uncertain. In 19 institutes, we prospectively enrolled hospitalized patients with advanced HF, who had plasma levels of B-type natriuretic peptide (BNP) >500 pg/ml on admission and BNP >300 pg/ml regardless of more than 1 week of medical therapy. Enrolled patients were randomized into Waon therapy or control groups. Waon therapy was performed once daily for 10 days with a far infrared-ray dry sauna maintained at 60℃ for 15 min, followed by bed rest for 30 min covered with a blanket. The primary endpoint was the ratio of BNP before and after treatment. In total, 76 Waon therapy and 73 control patients (mean age 66 years, men 61%, mean plasma BNP 777 pg/ml) were studied. The groups differed only in body mass index and the frequency of diabetes. The plasma BNP, NYHA classification, 6-min walk distance (6MWD), and cardiothoracic ratio significantly improved only in the Waon therapy group. Improvements in NYHA classification, 6MWD, and cardiothoracic ratio were significant in the Waon therapy group, although the change in plasma BNP did not reach statistical significance. No serious adverse events were observed in either group. Waon therapy, a holistic soothing warmth therapy, showed clinical advantages in safety and efficacy among patients with advanced HF.

  5. Advances in Cell Transplantation Therapy for Diseased Myocardium

    Directory of Open Access Journals (Sweden)

    Outi M. Villet

    2011-01-01

    Full Text Available The overall objective of cell transplantation is to repopulate postinfarction scar with contractile cells, thus improving systolic function, and to prevent or to regress the remodeling process. Direct implantation of isolated myoblasts, cardiomyocytes, and bone-marrow-derived cells has shown prospect for improved cardiac performance in several animal models and patients suffering from heart failure. However, direct implantation of cultured cells can lead to major cell loss by leakage and cell death, inappropriate integration and proliferation, and cardiac arrhythmia. To resolve these problems an approach using 3-dimensional tissue-engineered cell constructs has been investigated. Cell engineering technology has enabled scaffold-free sheet development including generation of communication between cell graft and host tissue, creation of organized microvascular network, and relatively long-term survival after in vivo transplantation.

  6. Specifically targeted gene therapy for small-cell lung cancer

    DEFF Research Database (Denmark)

    Christensen, C.L.; Zandi, R.; Gjetting, T.

    2009-01-01

    Small-cell lung cancer (SCLC) is a highly malignant disease with poor prognosis. Hence, there is great demand for new therapies that can replace or supplement the current available treatment regimes. Gene therapy constitutes a promising strategy and relies on the principle of introducing exogenous...

  7. ORAL-THERAPY FOR SMALL-CELL LUNG-CANCER

    NARCIS (Netherlands)

    POSTMUS, PE; SMIT, EF

    After a remarkable improvement of the very poor prognosis of small cell lung cancer with very simple therapy such as iv and oral cyclophosphamide the role of oral therapy has become minimal. However, since more than a decade results of combination chemotherapy are at a plateau and it is necessary to

  8. Hydroxyurea therapy in adult Nigerian sickle cell disease: a ...

    African Journals Online (AJOL)

    Background: The clinical prospects of hydroxyurea therapy in the management of sickle cell disease (SCD) require evaluation in the Nigerian setting to develop indigenous guidelines. This survey examines the pattern of hydroxyurea therapy, its clinico-haematologic benefits and safety profile in Nigerian SCD subjects.

  9. Evaluation of Fetuses in the Preventive IVIG Therapy for Congenital Heart Block (PITCH) study

    Science.gov (United States)

    Friedman, Deborah M.; Llanos, Carolina; Izmirly, Peter M.; Brock, Brigit; Byron, John; Copel, Joshua; Cummiskey, Karen; Anne Dooley, Mary; Foley, Jill; Graves, Cornelia; Hendershott, Collen; Kates, Richard; Komissarova, Elena V.; Miller, Michelle; Paré, Emmanuelle; Phoon, Colin K. L.; Prosen, Tracy; Reisner, Dale; Ruderman, Eric; Samuels, Philip; Yu, Jerry K.; Kim, Mimi Y.; Buyon, Jill P.

    2011-01-01

    Objective The recurrence rate of anti-SSA/Ro associated congenital heart block (CHB) is 17%. Reversal of 3rd degree block has never been achieved. Based on potential reduction of maternal autoantibody titers as well as fetal inflammatory responses, IVIG was evaluated as a preventative therapy for CHB. Methods A multicenter open-label study based on Simon’s 2-stage optimal design was initiated. Enrollment criteria included: maternal anti-SSA/Ro antibody, a previous child with CHB/rash, 400mg/kg) was given every 3 weeks from 12 to 24 weeks of gestation. The primary outcome was the development of 2nd or 3rd degree CHB. Results Twenty mothers completed the IVIG protocol before reaching the pre-determined stopping rule of three cases of advanced CHB. CHB was detected at 19, 20 and 25 weeks; none followed an abnormal PR interval. One of these mothers had two previous children with CHB. One child without CHB developed a transient rash consistent with neonatal lupus. Sixteen children had no manifestations of neonatal lupus at birth. No significant changes in maternal antibody titers to SSA/Ro, SSB/La, or Ro52 were detected over the course of therapy or at delivery. There were no safety issues. Conclusions IVIG at doses consistent with replacement does not prevent the recurrence of CHB or reduce maternal antibody titers. Having established safety with this protocol and feasibility of patient enrollment, subsequent preventative studies may be considered, perhaps to include higher doses of IVIG. PMID:20391423

  10. Stem cell based anti-HIV Gene therapy

    Science.gov (United States)

    Kitchen, Scott G.; Shimizu, Saki; An, Dong Sung

    2011-01-01

    Human stem cell-based therapeutic intervention strategies for treating HIV infection have recently undergone a renaissance as a major focus of investigation. Unlike most conventional antiviral therapies, genetically engineered hematopoietic stem cells possess the capacity for prolonged self-renewal that would continuously produce protected immune cells to fight against HIV. A successful strategy therefore has the potential to stably control and ultimately eradicate HIV from patients by a single or minimal treatment. Recent progress in the development of new technologies and clinical trials sets the stage for the current generation of gene therapy approaches to combat HIV infection. In this review, we will discuss two major approaches that are currently underway in the development of stem cell-based gene therapy to target HIV: One that focuses on the protection of cells from productive infection with HIV, and the other that focuses on targeting immune cells to directly combat HIV infection. PMID:21247612

  11. Optimising Use of Evidence-Based Pharmacological Therapy in Heart Failure

    OpenAIRE

    KEN LEE CHIN

    2018-01-01

    Heart failure remains a major clinical and public health problem, but the optimal use of pharmacological and non-pharmacological treatments in patients with heart failure can further reduce mortality and morbidity. This doctoral thesis i) highlighted the 'treatment gap' in patients with chronic heart failure and reduced ejection fraction, ii) demonstrated that aspirin does not reduce the beneficial effects of eplerenone in patients with chronic heart failure and reduced ejection fraction, iii...

  12. Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure.

    Science.gov (United States)

    Singh, S N; Fletcher, R D; Fisher, S G; Singh, B N; Lewis, H D; Deedwania, P C; Massie, B M; Colling, C; Lazzeri, D

    1995-07-13

    Asymptomatic ventricular arrhythmias in patients with congestive heart failure are associated with increased rates of overall mortality and sudden death. Amiodarone is now used widely to prevent ventricular tachycardia and fibrillation. We conducted a trial to determine whether amiodarone can reduce overall mortality in patients with congestive heart failure and asymptomatic ventricular arrhythmias. We used a double-blind, placebo-controlled protocol in which 674 patients with symptoms of congestive heart failure, cardiac enlargement, 10 or more premature ventricular contractions per hour, and a left ventricular ejection fraction of 40 percent or less were randomly assigned to receive amiodarone (336 patients) or placebo (338 patients). The primary end point was overall mortality, and the median follow-up was 45 months (range, 0 to 54). There was no significant difference in overall mortality between the two treatment groups (P = 0.6). The two-year actuarial survival rate was 69.4 percent (95 percent confidence interval, 64.2 to 74.6) for the patients in the amiodarone group and 70.8 percent (95 percent confidence interval, 65.7 to 75.9) for those in the placebo group. At two years, the rate of sudden death was 15 percent in the amiodarone group and 19 percent in the placebo group (P = 0.43). There was a trend toward a reduction in overall mortality among the patients with nonischemic cardiomyopathy who received amiodarone (P = 0.07). Amiodarone was significantly more effective in suppressing ventricular arrhythmias and increased the left ventricular ejection fraction by 42 percent at two years. Although amiodarone was effective in suppressing ventricular arrhythmias and improving ventricular function, it did not reduce the incidence of sudden death or prolong survival among patients with heart failure, except for a trend toward reduced mortality among those with nonischemic cardiomyopathy.

  13. Infrared fluorescent protein 1.4 genetic labeling tracks engrafted cardiac progenitor cells in mouse ischemic hearts.

    Science.gov (United States)

    Chen, Lijuan; Phillips, M Ian; Miao, Hui-Lai; Zeng, Rong; Qin, Gangjian; Kim, Il-man; Weintraub, Neal L; Tang, Yaoliang

    2014-01-01

    Stem cell therapy has a potential for regenerating damaged myocardium. However, a key obstacle to cell therapy's success is the loss of engrafted cells due to apoptosis or necrosis in the ischemic myocardium. While many strategies have been developed to improve engrafted cell survival, tools to evaluate cell efficacy within the body are limited. Traditional genetic labeling tools, such as GFP-like fluorescent proteins (eGFP, DsRed, mCherry), have limited penetration depths in vivo due to tissue scattering and absorption. To circumvent these limitations, a near-infrared fluorescent mutant of the DrBphP bacteriophytochrome from Deinococcus radiodurans, IFP1.4, was developed for in vivo imaging, but it has yet to be used for in vivo stem/progenitor cell tracking. In this study, we incorporated IFP1.4 into mouse cardiac progenitor cells (CPCs) by a lentiviral vector. Live IFP1.4-labeled CPCs were imaged by their near-infrared fluorescence (NIRF) using an Odyssey scanner following overnight incubation with biliverdin. A significant linear correlation was observed between the amount of cells and NIRF signal intensity in in vitro studies. Lentiviral mediated IFP1.4 gene labeling is stable, and does not impact the apoptosis and cardiac differentiation of CPC. To assess efficacy of our model for engrafted cells in vivo, IFP1.4-labeled CPCs were intramyocardially injected into infarcted hearts. NIRF signals were collected at 1-day, 7-days, and 14-days post-injection using the Kodak in vivo multispectral imaging system. Strong NIRF signals from engrafted cells were imaged 1 day after injection. At 1 week after injection, 70% of the NIRF signal was lost when compared to the intensity of the day 1 signal. The data collected 2 weeks following transplantation showed an 88% decrease when compared to day 1. Our studies have shown that IFP1.4 gene labeling can be used to track the viability of transplanted cells in vivo.

  14. Cell therapy for liver diseases: current medicine and future promises.

    Science.gov (United States)

    Alejandra, Meza-Ríos; Juan, Armendáriz-Borunda; Ana, Sandoval-Rodríguez

    2015-06-01

    Liver diseases are a major health problem worldwide since they usually represent the main causes of death in most countries, causing excessive costs to public health systems. Nowadays, there are no efficient current therapies for most hepatic diseases and liver transplant is infrequent due to the availability of organs, cost and risk of transplant rejection. Therefore, alternative therapies for liver diseases have been developed, including cell-based therapies. Stem cells (SCs) are characterized by their self-renewing capacity, unlimited proliferation and differentiation under certain conditions into tissue- or organ-specific cells with special functions. Cell-based therapies for liver diseases have been successful in experimental models, showing anti-inflammatory, antifibrogenic and regenerative effects. Nowadays, clinical trials using SCs for liver pathologies are increasing in number, and those that have reached publication have achieved favorable effects, encouraging us to think that SCs will have a potential clinical use in a short time.

  15. Acceptability of stem cell therapy by pregnant women.

    Science.gov (United States)

    Hodges, Ryan J; Bardien, Nadia; Wallace, Euan

    2012-06-01

    Cell-based therapies may soon be used to treat disorders in the perinatal period. Our aim was to assess pregnant women's knowledge, attitudes, and acceptance of different types of stem cell therapies. Pregnant women attending an Australian tertiary center were asked to complete a questionnaire to seek their views on the potential therapeutic use of stem cells in the future. Outcome measures were women's acceptability of different types of stem cell therapies for themselves and their baby, ethical concerns, knowledge, and willingness to use stem cells for different indications. A total of 150 women completed the questionnaire. More women were happy to use any stem cell type (82%) than placental stem cells only (12.5%), adult stem cells only (2%), embryonic stem cells only (0), and 3.5 percent would not use. With respect to use for their baby, more women were happy to use any stem cell type (83%) than placental stem cells only (13%), embryonic stem cells only (2%), adult stem cells only (0), and 2 percent would not use. Ethical concerns were highest with embryonic stem cells (25%), than adult stem cells (11%), and placental stem cells (10%). Twelve percent of women were very confident and 66 percent reasonably confident with their knowledge, whereas 17 percent understood little and 5 percent reported no understanding. Acceptance of using any stem cell therapy was 75 percent for severe medical disorders, 57 percent for moderate disorders, and 25 percent for mild medical disorders. Pregnant women are confident with their knowledge of stem cells and overwhelmingly support their use to treat both themselves and their baby. The level of this support, however, is proportionate to the severity of the medical disorder. (BIRTH 39:2 June 2012). © 2012, Copyright the Authors Journal compilation © 2012, Wiley Periodicals, Inc.

  16. Cost-effectiveness of N-terminal pro-B-type natriuretic-guided therapy in elderly heart failure patients: results from TIME-CHF (Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure).

    Science.gov (United States)

    Sanders-van Wijk, Sandra; van Asselt, Antoinette D I; Rickli, Hans; Estlinbaum, Werner; Erne, Paul; Rickenbacher, Peter; Vuillomenet, Andre; Peter, Martin; Pfisterer, Matthias E; Brunner-La Rocca, Hans-Peter

    2013-02-01

    This study aimed to assess cost-effectiveness of N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided versus symptom-guided therapy in heart failure (HF) patients ≥60 years old. Cost-effectiveness of NT-proBNP guidance in HF patients is unclear. It may create additional costs with uncertain benefits. In the TIME-CHF (Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure), patients with left ventricular ejection fraction (LVEF) of ≤45% were randomized to receive intensified NT-proBNP-guided therapy or standard, symptom-guided therapy. For cost-effectiveness analysis, 467 (94%) patients (age 76 ± 7 years, 66% male) were eligible. Incremental cost-effectiveness was calculated as incremental costs per gained life-year and quality-adjusted life-year (QALY) within the 18-month trial period, as defined per protocol. NT-proBNP-guided therapy was dominant (i.e., more effective and less costly) over symptom-guided therapy, saving $2,979 USD (2.5 to 97.5% confidence interval [CI]: $8,758 to $3,265) per patient, with incremental effectiveness of +0.07 life-years and +0.05 QALYs. The probability of NT-proBNP-guided therapy being dominant was 80%, and the probability of saving 1 life-year or QALY at a cost of $50,000 was 97% and 93%, respectively. Exclusion of residence costs resulted in an incremental cost-effectiveness ratio (ICER) of $5,870 per life-year gained. Cost-effectiveness of NT-proBNP-guided therapy was most pronounced in patients CHF]; ISRCTN43596477). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  17. Cell Based Therapies: At Crossroads to find the right Cell source

    Directory of Open Access Journals (Sweden)

    Editorial

    2012-01-01

    Full Text Available Development of newer Cell Based therapies for various diseases and disorders which have limited therapeutic options, is on the rise with clinical trials on cell based therapies being registered all over the world every now and then. However a dilemma arises when it comes to the choosing the ideal source of Stem cells for therapy. Clinical applications of Hematopoietic Stem cells Transplantation (HSCT in the form of Bone Marrow Transplantation has been in practice since the 1950s (1 for malignant and non malignant haematological disorders and even for auto-immune disorders (since 1977 (2, with several reports on successful outcomes after HSCT. The dilemma in HSCT is whether to use allogeneic or autologous sources. While allogeneic sources have the advantage of the graft being devoid of cancer cells, as they are from a healthy donor, they have the risk of life-long Immunosuppression. Autologous Source is advantageous as it needs no immunosuppression but the risk of relapse is high. In adult stem cells, there have been several studies which have demonstrated the various levels of safety and efficacy of both Allogeneic and autologous adult cell sources for application in diseases of the cornea, Spinal Cord, Heart, Liver etc. Each time, a study is published, the patients and the physicians are thrown into a state of perplexity on which source of cell could offer the best possible solution to the various diseases. Next hopping onto Human Embryonic Stem cells, though they were discovered in 1998, the first Human Embryonic Stem cell trial was approved by the FDA in January 2009 but it could hit the road only in October 2010 (3. The trial was for spinal cord injury and a year later, the trial came to a halt in November 2011 when the company, which was financing and pursuing the trial, announced the discontinuation of the trial due to financial reasons (4. However it is worthwhile to note that it was the financial compulsion which led to the

  18. On the dynamic suction pumping of blood cells in tubular hearts

    CERN Document Server

    Battista, Nicholas A; Miller, Laura A

    2016-01-01

    Around the third week after gestation in embryonic development, the human heart consists only of a valvless tube, unlike a fully developed adult heart, which is multi-chambered. At this stage in development, the heart valves have not formed and so net flow of blood through the heart must be driven by a different mechanism. It is hypothesized that there are two possible mechanisms that drive blood flow at this stage - Liebau pumping (dynamic suction pumping or valveless pumping) and peristaltic pumping. We implement the immersed boundary method with adaptive mesh refinement (IBAMR) to numerically study the effect of hematocrit on the circulation around a valveless. Both peristalsis and dynamic suction pumping are considered. In the case of dynamic suction pumping, the heart and circulatory system is simplified as a flexible tube attached to a relatively rigid racetrack. For some Womersley number (Wo) regimes, there is significant net flow around the racetrack. We find that the addition of flexible blood cells ...

  19. p53 Modulates the Fate of Cardiac Progenitor Cells Ex Vivo and in the Diabetic Heart In Vivo

    Directory of Open Access Journals (Sweden)

    Ramaswamy Kannappan

    2017-02-01

    Full Text Available p53 is an important modulator of stem cell fate, but its role in cardiac progenitor cells (CPCs is unknown. Here, we tested the effects of a single extra-copy of p53 on the function of CPCs in the presence of oxidative stress mediated by doxorubicin in vitro and type-1 diabetes in vivo. CPCs were obtained from super-p53 transgenic mice (p53-tg, in which the additional allele is regulated in a manner similar to the endogenous protein. Old CPCs with increased p53 dosage showed a superior ability to sustain oxidative stress, repair DNA damage and restore cell division. With doxorubicin, a larger fraction of CPCs carrying an extra-copy of the p53 allele recruited γH2A.X reestablishing DNA integrity. Enhanced p53 expression resulted in a superior tolerance to oxidative stress in vivo by providing CPCs with defense mechanisms necessary to survive in the milieu of the diabetic heart; they engrafted in regions of tissue injury and in three days acquired the cardiomyocyte phenotype. The biological advantage provided by the increased dosage of p53 in CPCs suggests that this genetic strategy may be translated to humans to increase cellular engraftment and growth, critical determinants of successful cell therapy for the failing heart.

  20. Heart rate is associated with mortality in patients undergoing continuous renal replacement therapy.

    Science.gov (United States)

    Lee, Soojin; Lee, Yeonhee; Jang, Heejoon; Moon, Hongran; Kim, Dong Ki; Han, Seung Seok

    2017-09-01

    Heart rate (HR) is an essential vital sign based on the finding that HR beyond its normal range is associated with several conditions or diseases, including high mortality in several clinical settings. Nevertheless, the clinical implications of HR remain unresolved in patients undergoing continuous renal replacement therapy (CRRT). This retrospective cohort study included 828 patients who underwent CRRT due to acute kidney injury between 2010 and 2014. HR and other baseline parameters at the time of CRRT initiation were retrieved. The odds ratio (OR) of 30-day mortality was calculated using a multivariate logistic model. CRRT significantly lowered the HR of patients such that the pre- and post-CRRT HRs (average 6 hours) were 107 beats/min and 103 beats/min, respectively (P CRRT initiation, but not pre- or post-CRRT HR, had a significant relationship with mortality outcome. Based on this result, we divided patients into quartiles of HR at the time of CRRT initiation. Mortality OR in the 4th quartile HR group was 2.6 (1.78-3.92) compared with the 1st quartile HR group. This relationship remained consistent despite adjusting for 28 baseline covariates: OR, 1.7 (1.09-2.76); P = 0.020. However, HR was not associated with the weaning rate from CRRT. High HR at the time of CRRT initiation is subsequently related with high mortality. These results can be a basis for a future predictive model of CRRT-related mortality.

  1. Effects of Swedish Massage Therapy on Blood Pressure, Heart Rate, and Inflammatory Markers in Hypertensive Women

    Directory of Open Access Journals (Sweden)

    Izreen Supa’at

    2013-01-01

    Full Text Available Swedish Massage Therapy (SMT is known for its therapeutic relaxation effects. Hypertension is associated with stress and elevated endothelial inflammatory markers. This randomized control trial measured the effects of whole body SMT (massage group or resting (control group an hour weekly for four weeks on hypertensive women. Blood pressure (BP and heart rate (HR were measured before and after each intervention and endothelial inflammatory markers: vascular endothelial adhesion molecules 1 (VCAM-1 and intracellular adhesion molecules 1 (ICAM-1 were measured at baseline and after the last intervention. Massage group (n=8 showed significant systolic BP (SBP reduction of 12 mmHg (P=0.01 and diastolic BP (DBP reduction of 5 mmHg (P=0.01 after four sessions with no significant difference between groups. Reductions in HR were also seen in massage group after sessions 1, 3, and 4 with significant difference between groups. VCAM-1 showed significant reduction after four sessions: the massage group showed reduction of 998.05 ng/mL (P=0.03 and the control group of 375.70 ng/mL (P=0.01 with no significant differences between groups. There were no changes in ICAM-1. In conclusion, SMT or resting an hour weekly has effects on reducing BP, HR, and VCAM-1 in hypertensive women.

  2. Multi-Targeted Antithrombotic Therapy for Total Artificial Heart Device Patients.

    Science.gov (United States)

    Ramirez, Angeleah; Riley, Jeffrey B; Joyce, Lyle D

    2016-03-01

    To prevent thrombotic or bleeding events in patients receiving a total artificial heart (TAH), agents have been used to avoid adverse events. The purpose of this article is to outline the adoption and results of a multi-targeted antithrombotic clinical procedure guideline (CPG) for TAH patients. Based on literature review of TAH anticoagulation and multiple case series, a CPG was designed to prescribe the use of multiple pharmacological agents. Total blood loss, Thromboelastograph(®) (TEG), and platelet light-transmission aggregometry (LTA) measurements were conducted on 13 TAH patients during the first 2 weeks of support in our institution. Target values and actual medians for postimplant days 1, 3, 7, and 14 were calculated for kaolinheparinase TEG, kaolin TEG, LTA, and estimated blood loss. Protocol guidelines were followed and anticoagulation management reduced bleeding and prevented thrombus formation as well as thromboembolic events in TAH patients postimplantation. The patients in this study were susceptible to a variety of possible complications such as mechanical device issues, thrombotic events, infection, and bleeding. Among them all it was clear that patients were at most risk for bleeding, particularly on postoperative days 1 through 3. However, bleeding was reduced into postoperative days 3 and 7, indicating that acceptable hemostasis was achieved with the anticoagulation protocol. The multidisciplinary, multi-targeted anticoagulation clinical procedure guideline was successful to maintain adequate antithrombotic therapy for TAH patients.

  3. Role of Negative-Pressure Wound Therapy in Deep Sternal Wound Infection After Open Heart Surgery

    Directory of Open Access Journals (Sweden)

    Cemalettin Aydın

    2013-08-01

    Full Text Available Introduction: Mediastinitis is a devastating complication in open heart surgery. The most common treatments after debridement are rewiring with antibiotic irrigation. Vacuum assisted closure therapy is a recently introduced technique that promotes the healing of difficult wounds, including post-sternotomy mediastinitis.Patients and Methods: Forty one patients with deep sternal wound infection were divided into two groups based on the treatment method used. Twenty two patients with post-cardio to my deep sternal wound infection were treated primarily by vacuum assisted closure method (group A and 19 patients with deep sternal wound infection who received closed mediastinal irrigation were treated with antibiotics (group B between January 2006 and January 2010.Results: The two groups were compared. Three patients died during treatment in group B. The median healing time was significantly shorter in group A (mean, 13.5 ± 3.2 days compared to 18 days (mean, 21.2 ± 16.4 days in group B (p< 0.001. Deep sternal wound infection showed no recurrences after the vacuum treatment, while 7 (24% patients in group B suffered recurrences. Hospital stay was significantly shorter in group A (median, 30.5 days; mean, 32.2 ± 11.3 days vs. median, 45 days; mean, 49.2 ± 19.3 days (p= 0.001.Conclusion: A significantly shorter healing time was confirmed with vacuum assisted closure. Hospital stay remained significantly shorter in group A (35 vs. 46 days.

  4. Changes in Heart Rate Variability of Depressed Patients after Electroconvulsive Therapy

    Directory of Open Access Journals (Sweden)

    Erica B. Royster

    2012-01-01

    Full Text Available Objective. As few, small studies have examined the impact of electroconvulsive therapy (ECT upon the heart rate variability of patients with major depressive disorder (MDD, we sought to confirm whether ECT-associated improvement in depressive symptoms would be associated with increases in HRV linear and nonlinear parameters. Methods. After providing consent, depressed study participants (n=21 completed the Beck Depression Index (BDI, and 15-minute Holter monitor recordings, prior to their 1st and 6th ECT treatments. Holter recordings were analyzed for certain HRV indices: root mean square of successive differences (RMSSD, low-frequency component (LF/high-frequency component (HF and short-(SD1 versus long-term (SD2 HRV ratios. Results. There were no significant differences in the HRV indices of RMSDD, LF/HF, and SD1/SD2 between the patients who responded, and those who did not, to ECT. Conclusion. In the short term, there appear to be no significant improvement in HRV in ECT-treated patients whose depressive symptoms respond versus those who do not. Future studies will reveal whether diminished depressive symptoms with ECT are reliably associated with improved sympathetic/parasympathetic balance over the long-term, and whether acute changes in sympathetic/parasympathetic balance predict improved mental- and cardiac-related outcomes.

  5. Characteristic of c-Kit+ progenitor cells in explanted human hearts.

    Science.gov (United States)

    Matuszczak, Sybilla; Czapla, Justyna; Jarosz-Biej, Magdalena; Wiśniewska, Ewa; Cichoń, Tomasz; Smolarczyk, Ryszard; Kobusińska, Magdalena; Gajda, Karolina; Wilczek, Piotr; Sliwka, Joanna; Zembala, Michał; Zembala, Marian; Szala, Stanisław

    2014-09-01

    According to literature data, self-renewing, multipotent, and clonogenic cardiac c-Kit(+) progenitor cells occur within human myocardium. The aim of this study was to isolate and characterize c-Kit(+) progenitor cells from explanted human hearts. Experimental material was obtained from 19 adult and 7 pediatric patients. Successful isolation and culture was achieved for 95 samples (84.1%) derived from five different regions of the heart: right and left ventricles, atrium, intraventricular septum, and apex. The average percentage of c-Kit(+) cells, as assessed by FACS, ranged between 0.7 and 0.9%. In contrast to published data we do not observed statistically significant differences in the number of c-Kit(+) cells between disease-specific groups, parts of the heart or sexes. Nevertheless, c-Kit(+) cells were present in significant numbers (11-24%) in samples derived from three explanted pediatric hearts. c-Kit(+) cells were also positive for CD105 and a majority of them was positive for CD31 and CD34 (83.7 ± 8.6 and 75.7 ± 11.4%, respectively). Immunohistochemical analysis of the heart tissue revealed that most cells possessing the c-Kit antigen were also positive for tryptase, a specific mast cell marker. However, flow cytometry analysis has shown cultured c-Kit(+) cells to be negative for hematopoietic marker CD45 and mast cell marker CD33. Isolated c-Kit(+) cells display mesenchymal stem cell features and are thought to differentiate into endothelial cells.

  6. Externally Applied Static Magnetic Field Enhances Cardiac Retention and Functional Benefit of Magnetically Iron-Labeled Adipose-Derived Stem Cells in Infarcted Hearts

    OpenAIRE

    Wang, Jian; Xiang, Bo; Deng, Jixian; Lin, Hung-Yu; Zheng, Dayang; Freed, Darren H.; Arora, Rakesh C.; Tian, Ganghong

    2016-01-01

    Although adipose-derived stem cells (ASCs) hold the promise of effective therapy for myocardial infarction (MI), low cardiac retention of implanted ASCs has hindered their therapeutic efficiency. We investigated whether an externally applied static magnetic field (SMF) enhanced cardiac localization of “magnetic” ASCs preloaded with superparamagnetic iron oxide (SPIO) nanoparticles and further improved heart function recovery. In conclusion, the SMF increased the cardiac retention of implanted...

  7. Stem Cell Therapy for Neonatal Hypoxic-Ischemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Gabriel eGonzales-Portillo

    2014-08-01

    Full Text Available Treatments for neonatal hypoxic ischemic encephalopathy (HIE have been limited. The aim of this paper is to offer translational research guidance on stem cell therapy for neonatal HIE by examining clinically relevant animal models, practical stem cell sources, safety and efficacy of endpoint assays, as well as a general understanding of modes of action of this cellular therapy. In order to do so, we discuss the clinical manifestations of HIE, highlighting its overlapping pathologies with stroke providing insights on the potential of cell therapy, currently investigated in stroke, for HIE. To this end, we draw guidance from recommendations outlined in Stem cell Therapeutics as an Emerging Paradigm for Stroke or STEPS, which have been recently modified to Baby STEPS to cater for the neonatal symptoms of HIE. These guidelines recognized that neonatal HIE exhibits distinct disease symptoms from adult stroke in need of an innovative translational approach that facilitates the entry of cell therapy in the clinic. Finally, new information about recent clinical trials, and insights into combination therapy are provided with the vision that stem cell therapy may benefit from available treatments, such as hypothermia, already being tested in children diagnosed with HIE.

  8. Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Encapsulating Bioactive Hydrogels Improve Rat Heart Function Post Myocardial Infarction.

    Science.gov (United States)

    Chow, Andre; Stuckey, Daniel J; Kidher, Emaddin; Rocco, Mark; Jabbour, Richard J; Mansfield, Catherine A; Darzi, Ara; Harding, Sian E; Stevens, Molly M; Athanasiou, Thanos

    2017-10-04

    Tissue engineering offers an exciting possibility for cardiac repair post myocardial infarction. We assessed the effects of combined polyethylene glycol hydrogel (PEG), human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM), and erythropoietin (EPO) therapy in a rat model of myocardial infarction. PEG with/out iPSC-CMs and EPO; iPSC-CMs in saline; or saline alone was injected into infarcted hearts shortly after infarction. Injection of almost any combination of the therapeutics limited acute elevations in chamber volumes. After 10 weeks, attenuation of ventricular remodeling was identified in all groups that received PEG injections, while ejection fractions were significantly increased in the gel-EPO, cell, and gel-cell-EPO groups. In all treatment groups, infarct thickness was increased and regions of muscle were identified within the scar. However, no grafted cells were detected. Hence, iPSC-CM-encapsulating bioactive hydrogel therapy can improve cardiac function post myocardial infarction and increase infarct thickness and muscle content despite a lack of sustained donor-cell engraftment. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. New Advanced Technologies In Stem Cell Therapy

    Science.gov (United States)

    2011-09-01

    proliferation media or PROe media since the cell isolation and were designated ST2 and ST2e, respectively. The 12-well plate was place on a Live Cell Imaging system...to 12 passages. Cells were then transferred to 24 well plates and proliferation measured using a previously described Live Cell Imaging (LCI...MDSCs, we used a previously described live cell imaging system [LCI] (Kairos Instruments LLC) 15. Brightfield images were taken at a 100x

  10. Cytokine production profile of heart-infiltrating T cells in Chagas' disease cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Cunha-Neto E.

    1998-01-01

    Full Text Available The hallmark of chronic Chagas' disease cardiomyopathy (CCC is the finding of a T cell-rich inflammatory mononuclear cell infiltrate in the presence of extremely few parasites in the heart lesions. The scarcity of parasites in affected heart tissue casts doubt on the direct participation of Trypanosoma cruzi in CCC heart tissue lesions, and suggests the possible involvement of autoimmunity. The cells in the infiltrate are presumably the ultimate effectors of tissue damage, and there is evidence that such cells recognize cardiac myosin in molecular mimicry with T. cruzi proteins rather than primary reactivity to T. cruzi antigens (Cunha-Neto et al. (1996 Journal of Clinical Investigation, 98: 1709-1712. Recently, we have studied heart-infiltrating T cells at the functional level. In this short review we summarize the studies about the role of cytokines in human and experimental T. cruzi infection, along with our data on heart-infiltrating T cells in human Chagas' cardiomyopathy. The bulk of evidence points to a significant production of IFN-g and TNF-a which may be linked to T. cruzi-induced IL-12 production

  11. Association between β-blocker therapy and outcomes in patients hospitalised with acute exacerbations of chronic obstructive lung disease with underlying ischaemic heart disease, heart failure or hypertension.

    Science.gov (United States)

    Stefan, Mihaela S; Rothberg, Michael B; Priya, Aruna; Pekow, Penelope S; Au, David H; Lindenauer, Peter K

    2012-11-01

    β-Blocker therapy has been shown to improve survival among patients with ischaemic heart disease (IHD) and congestive heart failure (CHF) and is underused among patients with chronic obstructive pulmonary disease (COPD). Evidence regarding the optimal use of β-blocker therapy during an acute exacerbation of COPD is particularly weak. We conducted a retrospective cohort study of patients aged ≥40 years with IHD, CHF or hypertension who were hospitalised for an acute exacerbation of COPD from 1 January 2006 to 1 December 2007 at 404 acute care hospitals throughout the USA. We examined the association between β-blocker therapy and in-hospital mortality, initiation of mechanical ventilation after day 2 of hospitalisation, 30-day all-cause readmission and length of stay. Of 35 082 patients who met the inclusion criteria, 29% were treated with β blockers in the first two hospital days, including 22% with β1-selective and 7% with non-selective β blockers. In a propensity-matched analysis, there was no association between β-blocker therapy and in-hospital mortality (OR 0.88, 95% CI 0.71 to 1.09), 30-day readmission (OR 0.96, 95% CI 0.89 to 1.03) or late mechanical ventilation (OR 0.98, 95% CI 0.77 to 1.24). However, when compared with β1 selective β blockers, receipt of non-selective β blockers was associated with an increased risk of 30-day readmission (OR 1.25, 95% CI 1.08 to 1.44). Among patients with IHD, CHF or hypertension, continuing β1-selective β blockers during hospitalisation for COPD appears to be safe. Until additional evidence becomes available, β1-selective β blockers may be superior to treatment with a non-selective β blocker.

  12. Imperative role of dental pulp stem cells in regenerative therapies: A systematic review

    Directory of Open Access Journals (Sweden)

    Ramchandra Kabir

    2014-01-01

    Full Text Available Stem cells are primitive cells that can differentiate and regenerate organs in different parts of the body such as heart, bones, muscles and nervous system. This has been a field of great clinical interest with immense possibilities of using the stem cells in regeneration of human organ those are damaged due to disease, developmental defects and accident. The knowledge of stem cell technology is increasing quickly in all medical specialties and in dental field too. Stem cells of dental origin appears to hold the key to various cell-based therapies in regenerative medicine, but most avenues are in experimental stages and many procedures are undergoing standardization and validation. Long-term preservation of SHED cells or DPSC is becoming a popular consideration, similar to the banking of umbilical cord blood. Dental pulp stem cells (DPSCs are the adult multipotent cells that reside in the cell rich zone of the dental pulp. The multipotent nature of these DPSCs may be utilized in both dental and medical applications. A systematic review of the literature was performed using various internet based search engines (PubMed, Medline Plus, Cochrane, Medknow, Ebsco, Science Direct, Hinari, WebMD, IndMed, Embase using keywords like "dental pulp stem cells", "regeneration", "medical applications", "tissue engineering". DPSCs appears to be a promising innovation for the re-growth of tissues however, long term clinical studies need to be carried out that could establish some authentic guidelines in this perspective.

  13. Heart failure in patients with kidney disease and iron deficiency: The role of iron therapy

    Directory of Open Access Journals (Sweden)

    Aleix Cases Amenós

    2017-11-01

    Full Text Available Chronic kidney disease and anaemia are common in heart failure (HF and are associated with a worse prognosis in these patients. Iron deficiency is also common in patients with HF and increases the risk of morbidity and mortality, regardless of the presence or absence of anaemia. While the treatment of anaemia with erythropoiesis-stimulating agents in patients with HF have failed to show a benefit in terms of morbidity and mortality, treatment with IV iron in patients with HF and reduced ejection fraction and iron deficiency is associated with clinical improvement. In a post hoc analysis of a clinical trial, iron therapy improved kidney function in patients with HF and iron deficiency. In fact, the European Society of Cardiology's recent clinical guidelines on HF suggest that in symptomatic patients with reduced ejection fraction and iron deficiency, treatment with IV ferric carboxymaltose should be considered to improve symptoms, the ability to exercise and quality of life. Iron plays a key role in oxygen storage (myoglobin and in energy metabolism, and there are pathophysiological bases that explain the beneficial effect of IV iron therapy in patients with HF. All these aspects are reviewed in this article. Resumen: La enfermedad renal crónica y la anemia son frecuentes en la insuficiencia cardíaca (IC y su presencia se asocia con un peor pronóstico en estos pacientes. La ferropenia es frecuente en pacientes con IC y aumenta el riesgo de morbimortalidad, independientemente de la presencia o no de anemia. Mientras el tratamiento de la anemia con agentes estimuladores de la eritropoyesis en pacientes con IC no ha demostrado un beneficio sobre la morbimortalidad, el tratamiento con hierro intravenoso (iv en pacientes con IC y fracción de eyección disminuida y déficit de hierro se asocia con una mejoría clínica. Además, en un análisis post hoc de un ensayo clínico, la ferroterapia mejoró la función renal en pacientes con IC y

  14. Methods for Stem Cell Production and Therapy

    Science.gov (United States)

    Claudio, Pier Paolo (Inventor); Valluri, Jagan V. (Inventor)

    2015-01-01

    The present invention relates to methods for rapidly expanding a stem cell population with or without culture supplements in simulated microgravity conditions. The present invention relates to methods for rapidly increasing the life span of stem cell populations without culture supplements in simulated microgravity conditions. The present invention also relates to methods for increasing the sensitivity of cancer stem cells to chemotherapeutic agents by culturing the cancer stem cells under microgravity conditions and in the presence of omega-3 fatty acids. The methods of the present invention can also be used to proliferate cancer cells by culturing them in the presence of omega-3 fatty acids. The present invention also relates to methods for testing the sensitivity of cancer cells and cancer stem cells to chemotherapeutic agents by culturing the cancer cells and cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce tissue for use in transplantation by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors to promote differentiation of cancer stem cells under microgravity conditions.

  15. Leukocytoclastic Vasculitis as a Complication of Recombinant Granulocyte Colony-Stimulating Factor Therapy in a Heart Transplant Patient

    Directory of Open Access Journals (Sweden)

    Giovanbattista Ippoliti

    2014-01-01

    Full Text Available Recombinant granulocyte colony-stimulating factor (rG-CSF is a myeloid growth factor that is widely used in haematology to recover neutropenia secondary to myelosuppressive chemotherapy. Leukocytoclastic vasculitis is an acknowledged side effect of the above therapy. Its pathogenesis involves many mechanisms that collectively induce an increase in neutrophil function and a subsequent release of cytokines. Here, we report a case of leukocytoclastic vasculitis proven by skin biopsy, following the use of rG-CSF in a heart transplant patient with leukopenia secondary to immunosuppressive therapy.

  16. Simple Method to Estimate Mean Heart Dose From Hodgkin Lymphoma Radiation Therapy According to Simulation X-Rays

    Energy Technology Data Exchange (ETDEWEB)

    Nimwegen, Frederika A. van [Department of Psychosocial Research, Epidemiology, and Biostatistics, The Netherlands Cancer Institute, Amsterdam (Netherlands); Cutter, David J. [Clinical Trial Service Unit, University of Oxford, Oxford (United Kingdom); Oxford Cancer Centre, Oxford University Hospitals NHS Trust, Oxford (United Kingdom); Schaapveld, Michael [Department of Psychosocial Research, Epidemiology, and Biostatistics, The Netherlands Cancer Institute, Amsterdam (Netherlands); Rutten, Annemarieke [Department of Radiology, The Netherlands Cancer Institute, Amsterdam (Netherlands); Kooijman, Karen [Department of Psychosocial Research, Epidemiology, and Biostatistics, The Netherlands Cancer Institute, Amsterdam (Netherlands); Krol, Augustinus D.G. [Department of Radiation Oncology, Leiden University Medical Center, Leiden (Netherlands); Janus, Cécile P.M. [Department of Radiation Oncology, Erasmus MC Cancer Center, Rotterdam (Netherlands); Darby, Sarah C. [Clinical Trial Service Unit, University of Oxford, Oxford (United Kingdom); Leeuwen, Flora E. van [Department of Psychosocial Research, Epidemiology, and Biostatistics, The Netherlands Cancer Institute, Amsterdam (Netherlands); Aleman, Berthe M.P., E-mail: b.aleman@nki.nl [Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam (Netherlands)

    2015-05-01

    Purpose: To describe a new method to estimate the mean heart dose for Hodgkin lymphoma patients treated several decades ago, using delineation of the heart on radiation therapy simulation X-rays. Mean heart dose is an important predictor for late cardiovascular complications after Hodgkin lymphoma (HL) treatment. For patients treated before the era of computed tomography (CT)-based radiotherapy planning, retrospective estimation of radiation dose to the heart can be labor intensive. Methods and Materials: Patients for whom cardiac radiation doses had previously been estimated by reconstruction of individual treatments on representative CT data sets were selected at random from a case–control study of 5-year Hodgkin lymphoma survivors (n=289). For 42 patients, cardiac contours were outlined on each patient's simulation X-ray by 4 different raters, and the mean heart dose was estimated as the percentage of the cardiac contour within the radiation field multiplied by the prescribed mediastinal dose and divided by a correction factor obtained by comparison with individual CT-based dosimetry. Results: According to the simulation X-ray method, the medians of the mean heart doses obtained from the cardiac contours outlined by the 4 raters were 30 Gy, 30 Gy, 31 Gy, and 31 Gy, respectively, following prescribed mediastinal doses of 25-42 Gy. The absolute-agreement intraclass correlation coefficient was 0.93 (95% confidence interval 0.85-0.97), indicating excellent agreement. Mean heart dose was 30.4 Gy with the simulation X-ray method, versus 30.2 Gy with the representative CT-based dosimetry, and the between-method absolute-agreement intraclass correlation coefficient was 0.87 (95% confidence interval 0.80-0.95), indicating good agreement between the two methods. Conclusion: Estimating mean heart dose from radiation therapy simulation X-rays is reproducible and fast, takes individual anatomy into account, and yields results comparable to the labor

  17. Dental Stem Cell in Tooth Development and Advances of Adult Dental Stem Cell in Regenerative Therapies.

    Science.gov (United States)

    Tan, Jiali; Xu, Xin; Lin, Jiong; Fan, Li; Zheng, Yuting; Kuang, Wei

    2015-01-01

    Stem cell-based therapies are considered as a promising treatment for many clinical usage such as tooth regeneration, bone repairation, spinal cord injury, and so on. However, the ideal stem cell for stem cell-based therapy still remains to be elucidated. In the past decades, several types of stem cells have been isolated from teeth, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), dental follicle progenitor stem cells (DFPCs) and stem cells from apical papilla (SCAP), which may be a good source for stem cell-based therapy in certain disease, especially when they origin from neural crest is considered. In this review, the specific characteristics and advantages of the adult dental stem cell population will be summarized and the molecular mechanisms of the differentiation of dental stem cell during tooth development will be also discussed.

  18. Effect of repeated intracoronary injection of bone marrow cells in patients with ischaemic heart failure the Danish stem cell study--congestive heart failure trial (DanCell-CHF)

    DEFF Research Database (Denmark)

    Diederichsen, Axel Cosmus Pyndt; Møller, Jacob E; Thayssen, Per

    2008-01-01

    BACKGROUND: It has been suggested that myocardial regeneration may be achieved by a single intracoronary bone marrow derived stem cell infusion in selected patients with ischaemic heart disease. The effect is uncertain in patients with chronic ischaemic heart failure and it is not known whether r...

  19. Market access pathways for cell therapies in France.

    Science.gov (United States)

    Rémuzat, Cécile; Toumi, Mondher; Jørgensen, Jesper; Kefalas, Panos

    2015-01-01

    Cell therapies can be classified into three main categories of products: advanced therapy medicinal products (ATMPs), ATMPs prepared on a non-routine basis (hospital exemptions), and minimally manipulated cells. Despite the benefits that cell therapies can bring to patients, they are subject to complex pathways to reach the market in France. The objective of this study was to identify and describe routes to market access for cell therapies in France and how these vary by regulatory status. The research was structured following five main steps: (1) identification of the French regulatory framework for cell therapies; (2) identification of the health products categorised as cell therapies in France; (3) mapping of the market access pathways per category of cell therapy; (4) validation of findings by interviewing experts; and (5) development of a roadmap summarising market access pathways for cell therapies in France. The secondary research methodology included a comprehensive literature review conducted on websites of French public health institutions, complemented by a research for peer-reviewed articles, abstracts, and grey literature. Different market access pathways are possible depending on the cell therapy category. For ATMPs, market access pathways depend on the licensing status of the therapy. Licensed ATMPs followed the same market access pathways as 'conventional' pharmaceuticals, whereas not-yet-licensed ATMPs can be funded via a specific financial allowance under the framework of a Temporary Authorisation for Use procedure or various research programmes. For new ATMPs that are associated with a separate medical device (not considered as 'combined ATMPs') or associated with a new medical procedure, additional pathways will apply for the medical device and/or medical procedure to be reimbursed in the ambulatory settings or at hospital. The most likely funding option for ATMPs prepared on a non-routine basis is outside the diagnosis-related group (DRG

  20. Pulmonary heart valve replacement using stabilized acellular xenogeneic scaffolds; effects of seeding with autologous stem cells

    Directory of Open Access Journals (Sweden)

    Harpa Marius Mihai

    2015-12-01

    Full Text Available Background: We hypothesized that an ideal heart valve replacement would be acellular valve root scaffolds seeded with autologous stem cells. To test this hypothesis, we prepared porcine acellular pulmonary valves, seeded them with autologous adipose derived stem cells (ADSCs and implanted them in sheep and compared them to acellular valves.

  1. T cell subsets: an integral component in pathogenesis of rheumatic heart disease.

    Science.gov (United States)

    Toor, Devinder; Sharma, Neha

    2018-02-01

    Acute rheumatic fever (ARF) is a consequence of pharyngeal infection of group A streptococcal (GAS) infection. Carditis is the most common manifestation of ARF which occurs in 30-45% of the susceptible individuals. Overlooked ARF cases might further progress towards rheumatic heart disease (RHD) in susceptible individuals, which ultimately leads to permanent heart valve damage. Molecular mimicry between streptococcal antigens and human proteins is the most widely accepted theory to describe the pathogenesis of RHD. In the recent past, various subsets of T cells have been reported to play an imperative role in the pathogenesis of RHD. Alterations in various T cell subsets, viz. Th1, Th2, Th17, and Treg cells, and their signature cytokines influence the immune responses and are associated with pathogenesis of RHD. Association of other T cell subsets (Th3, Th9, Th22, and T FH ) is not defined in context of RHD. Several investigations have confirmed the up-regulation of adhesion molecules and thus infiltration of T cells into the heart tissues. T cells secrete both Th type 1 and type 2 cytokines and these auto-reactive T cells play a key role in progression of heart valve damage. In this review, we are going to discuss about the role of T cell subsets and their corresponding cytokines in the pathogenesis of RHD.

  2. Stem cell transplantation therapy for multifaceted therapeutic benefits after stroke.

    Science.gov (United States)

    Wei, Ling; Wei, Zheng Z; Jiang, Michael Qize; Mohamad, Osama; Yu, Shan Ping

    2017-10-01

    One of the exciting advances in modern medicine and life science is cell-based neurovascular regeneration of damaged brain tissues and repair of neuronal structures. The progress in stem cell biology and creation of adult induced pluripotent stem (iPS) cells has significantly improved basic and pre-clinical research in disease mechanisms and generated enthusiasm for potential applications in the treatment of central nervous system (CNS) diseases including stroke. Endogenous neural stem cells and cultured stem cells are capable of self-renewal and give rise to virtually all types of cells essential for the makeup of neuronal structures. Meanwhile, stem cells and neural progenitor cells are well-known for their potential for trophic support after transplantation into the ischemic brain. Thus, stem cell-based therapies provide an attractive future for protecting and repairing damaged brain tissues after injury and in various disease states. Moreover, basic research on naïve and differentiated stem cells including iPS cells has markedly improved our understanding of cellular and molecular mechanisms of neurological disorders, and provides a platform for the discovery of novel drug targets. The latest advances indicate that combinatorial approaches using cell based therapy with additional treatments such as protective reagents, preconditioning strategies and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the characteristics of cell therapy in different ischemic models and the application of stem cells and progenitor cells as regenerative medicine for the treatment of stroke. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Gene therapy for oral squamous cell carcinoma: An overview

    Directory of Open Access Journals (Sweden)

    Saraswathi T

    2007-01-01

    Full Text Available A potential approach to the treatment of genetic disorders is gene therapy. The goal of gene therapy is to introduce therapeutic genetic material into the target cell to exert the intended therapeutic effect. Gene therapy has already shown promising results for the treatment of monogenic disorders such as severe combined immunodeficiency and haemophilia. Now the procedure has been extended to the level of treating malignant conditions such as cancer of the lungs, breast, colon etc. The prevalence of tumours of the larynx and oral cavity has increased in both developed and developing countries. This increase underscores the need for a novel therapeutic modality that would decrease or completely terminate the proliferation of malignant cells. This review highlights various types of gene therapy procedures with respect to oral squamous cell carcinoma.

  4. Interleukin-1{beta} regulates cell proliferation and activity of extracellular matrix remodelling enzymes in cultured primary pig heart cells

    Energy Technology Data Exchange (ETDEWEB)

    Zitta, Karina; Brandt, Berenice [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany); Wuensch, Annegret [Institute of Molecular Animal Breeding and Biotechnology, Ludwig Maximilians University, Munich (Germany); Meybohm, Patrick; Bein, Berthold; Steinfath, Markus; Scholz, Jens [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany); Albrecht, Martin, E-mail: Albrecht@anaesthesie.uni-kiel.de [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany)

    2010-09-03

    Research highlights: {yields} Levels of IL-1{beta} are increased in the pig myocardium after infarction. {yields} Cultured pig heart cells possess IL-1 receptors. {yields} IL-1{beta} increases cell proliferation of pig heart cells in-vitro. {yields} IL-1{beta} increases MMP-2 and MMP-9 activity in pig heart cells in-vitro. {yields} IL-1{beta} may be important for tissue remodelling events after myocardial infarction. -- Abstract: After myocardial infarction, elevated levels of interleukins (ILs) are found within the myocardial tissue and IL-1{beta} is considered to play a major role in tissue remodelling events throughout the body. In the study presented, we have established a cell culture model of primary pig heart cells to evaluate the effects of different concentrations of IL-1{beta} on cell proliferation as well as expression and activity of enzymes typically involved in tissue remodelling. Primary pig heart cell cultures were derived from three different animals and stimulated with recombinant pig IL-1{beta}. RNA expression was detected by RT-PCR, protein levels were evaluated by Western blotting, activity of matrix metalloproteinases (MMPs) was quantified by gelatine zymography and cell proliferation was measured using colorimetric MTS assays. Pig heart cells express receptors for IL-1 and application of IL-1{beta} resulted in a dose-dependent increase of cell proliferation (P < 0.05 vs. control; 100 ng/ml; 24 h). Gene expression of caspase-3 was increased by IL-1{beta} (P < 0.05 vs. control; 100 ng/ml; 3 h), and pro-caspase-3 but not active caspase was detected in lysates of pig heart cells by Western blotting. MMP-2 gene expression as well as enzymatic activities of MMP-2 and MMP-9 were increased by IL-1{beta} (P < 0.05 vs. control; 100 ng/ml; 3 h for gene expression, 48 and 72 h for enzymatic activities of MMP-2 and MMP-9, respectively). Our in vitro data suggest that IL-1{beta} plays a major role in the events of tissue remodelling in the heart. Combined

  5. A protocol proposition of cell therapy for the treatment of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Ribeiro-Paes, J T; Stessuk, T; Marcelino, M; Faria, C; Marinelli, T; Ribeiro-Paes, M J

    2014-01-01

    The main feature of pulmonary emphysema is airflow obstruction resulting from the destruction of the alveolar walls distal to the terminal bronchioles. Existing clinical approaches have improved and extended the quality of life of emphysema patients. However, no treatment currently exists that can change the disease course and cure the patient. The different therapeutic approaches that are available aim to increase survival and/or enhance the quality of life of emphysema patients. In this context, cell therapy is a promising therapeutic approach with great potential for degenerative pulmonary diseases. In this protocol proposition, all patients will be submitted to laboratory tests, such as evaluation of heart and lung function and routine examinations. Stem cells will be harvested by means of 10 punctures on each anterior iliac crest, collecting a total volume of 200mL bone marrow. After preparation, separation, counting and labeling (optional) of the mononuclear cells, the patients will receive an intravenous infusion from the pool of Bone Marrow Mononuclear Cells (BMMC). This article proposes a rational and safe clinical cellular therapy protocol which has the potential for developing new projects and can serve as a methodological reference for formulating clinical application protocols related to the use of cellular therapy in COPD. This study protocol was submitted and approved by the Brazilian National Committee of Ethics in Research (CONEP - Brazil) registration number 14764. It is also registered in ClinicalTrials.gov (NCT01110252). Copyright © 2013 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

  6. Intra coronary freshly isolated bone marrow cells transplantation improve cardiac function in patients with ischemic heart disease

    Directory of Open Access Journals (Sweden)

    Bozdag-Turan Ilkay

    2012-04-01

    Full Text Available Abstract Background Autologous bone marrow cell transplantation (BMCs-Tx is a promising novel option for treatment of cardiovascular disease. In this study we analyzed whether intracoronary autologous freshly isolated BMCs-Tx have beneficial effects on cardiac function in patients with ischemic heart disease (IHD. Results In this prospective nonrandomized study we treated 12 patients with IHD by freshly isolated BMCs-Tx by use of point of care system and compared them with a representative 12 control group without cell therapy. Global ejection fraction (EF and infarct size area were determined by left ventriculography. Intracoronary transplantation of autologous freshly isolated BMCs led to a significant reduction of infarct size (p  Conclusions These results demonstrate that intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system is safe and may lead to improvement of cardiac function in patients with IHD. Trial registration Registration number: ISRCTN54510226

  7. Multimodality Molecular Imaging of Stem Cells Therapy for Stroke

    Directory of Open Access Journals (Sweden)

    Fangfang Chao

    2013-01-01

    Full Text Available Stem cells have been proposed as a promising therapy for treating stroke. While several studies have demonstrated the therapeutic benefits of stem cells, the exact mechanism remains elusive. Molecular imaging provides the possibility of the visual representation of biological processes at the cellular and molecular level. In order to facilitate research efforts to understand the stem cells therapeutic mechanisms, we need to further develop means of monitoring these cells noninvasively, longitudinally and repeatedly. Because of tissue depth and the blood-brain barrier (BBB, in vivo imaging of stem cells therapy for stroke has unique challenges. In this review, we describe existing methods of tracking transplanted stem cells in vivo, including magnetic resonance imaging (MRI, nuclear medicine imaging, and optical imaging (OI. Each of the imaging techniques has advantages and drawbacks. Finally, we describe multimodality imaging strategies as a more comprehensive and potential method to monitor transplanted stem cells for stroke.

  8. Interleukin-1beta regulates cell proliferation and activity of extracellular matrix remodelling enzymes in cultured primary pig heart cells.

    Science.gov (United States)

    Zitta, Karina; Brandt, Berenice; Wuensch, Annegret; Meybohm, Patrick; Bein, Berthold; Steinfath, Markus; Scholz, Jens; Albrecht, Martin

    2010-09-03

    After myocardial infarction, elevated levels of interleukins (ILs) are found within the myocardial tissue and IL-1beta is considered to play a major role in tissue remodelling events throughout the body. In the study presented, we have established a cell culture model of primary pig heart cells to evaluate the effects of different concentrations of IL-1beta on cell proliferation as well as expression and activity of enzymes typically involved in tissue remodelling. Primary pig heart cell cultures were derived from three different animals and stimulated with recombinant pig IL-1beta. RNA expression was detected by RT-PCR, protein levels were evaluated by Western blotting, activity of matrix metalloproteinases (MMPs) was quantified by gelatine zymography and cell proliferation was measured using colorimetric MTS assays. Pig heart cells express receptors for IL-1 and application of IL-1beta resulted in a dose-dependent increase of cell proliferation (Ppig heart cells by Western blotting. MMP-2 gene expression as well as enzymatic activities of MMP-2 and MMP-9 were increased by IL-1beta (Pheart. Combined with our recently published in vivo data (Meybohm et al., PLoS One, 2009), the results presented here strongly suggest IL-1beta as a key molecule guiding tissue remodelling events after myocardial infarction. Copyright 2010 Elsevier Inc. All rights reserved.

  9. Progenitor cells from the heart - Cellulae Progenitores Cordis

    NARCIS (Netherlands)

    Vliet, Patrick van

    2009-01-01

    Myocardial infarction is a leading cause of high mortality rates in Western countries. After ischemia, lost cardiomyocytes are replaced by fibrotic tissue, while remaining cardiomyocytes hypertrophy, both further impairing ventricular function. Current therapies consist of restoration of reperfusion

  10. Imperative Role of Dental Pulp Stem Cells in Regenerative Therapies: A Systematic Review

    Science.gov (United States)

    Kabir, Ramchandra; Gupta, Manish; Aggarwal, Avanti; Sharma, Deepak; Sarin, Anurag; Kola, Mohammed Zaheer

    2014-01-01

    Stem cells are primitive cells that can differentiate and regenerate organs in different parts of the body such as heart, bones, muscles and nervous system. This has been a field of great clinical interest with immense possibilities of using the stem cells in regeneration of human organ those are damaged due to disease, developmental defects and accident. The knowledge of stem cell technology is increasing quickly in all medical specialties and in dental field too. Stem cells of dental origin appears to hold the key to various cell-based therapies in regenerative medicine, but most avenues are in experimental stages and many procedures are undergoing standardization and validation. Long-term preservation of SHED cells or DPSC is becoming a popular consideration, similar to the banking of umbilical cord blood. Dental pulp stem cells (DPSCs) are the adult multipotent cells that reside in the cell rich zone of the dental pulp. The multipotent nature of these DPSCs may be utilized in both dental and medical applications. A systematic review of the literature was performed using various internet based search engines (PubMed, Medline Plus, Cochrane, Medknow, Ebsco, Science Direct, Hinari, WebMD, IndMed, Embase) using keywords like “dental pulp stem cells”, “regeneration”, “medical applications”, “tissue engineering”. DPSCs appears to be a promising innovation for the re-growth of tissues however, long term clinical studies need to be carried out that could establish some authentic guidelines in this perspective. PMID:24665194

  11. Stem cell-based therapies for osteoarthritis: challenges and opportunities.

    Science.gov (United States)

    Diekman, Brian O; Guilak, Farshid

    2013-01-01

    Regenerative medicine offers the exciting potential of developing alternatives to total joint replacement for treating osteoarthritis. In this article, we highlight recent work that addresses key challenges of stem cell-based therapies for osteoarthritis and provide examples of innovative ways in which stem cells can aid in the treatment of osteoarthritis. Significant progress has been made in understanding the challenges to successful stem cell therapy, such as the effects of age or disease on stem cell properties, altered stem cell function due to an inflammatory joint environment and phenotypic instability in vivo. Novel scaffold designs have been shown to enhance the mechanical properties of tissue-engineered cartilage and have also improved the integration of newly formed tissue within the joint. Emerging strategies such as injecting stem cells directly into the joint, manipulating endogenous stem cells to enhance regenerative capacity and utilizing stem cells for drug discovery have expanded the potential uses of stem cells in treating osteoarthritis. Several recent studies have greatly advanced the development and preclinical evaluation of potential stem cell-based treatments for osteoarthritis through novel approaches focused on cell therapy, tissue engineering and drug discovery.

  12. Ethical issues in stem cell research and therapy.

    Science.gov (United States)

    King, Nancy Mp; Perrin, Jacob

    2014-07-07

    Rapid progress in biotechnology has introduced a host of pressing ethical and policy issues pertaining to stem cell research. In this review, we provide an overview of the most significant issues with which the stem cell research community should be familiar. We draw on a sample of the bioethics and scientific literatures to address issues that are specific to stem cell research and therapy, as well as issues that are important for stem cell research and therapy but also for translational research in related fields, and issues that apply to all clinical research and therapy. Although debate about the moral status of the embryo in human embryonic stem cell research continues to have relevance, the discovery of other highly multipotent stem cell types and alternative methods of isolating and creating highly multipotent stem cells has raised new questions and concerns. Induced pluripotent stem cells hold great promise, but care is needed to ensure their safety in translational clinical trials, despite the temptation to move quickly from bench to bedside. A variety of highly multipotent stem cells - such as mesenchymal stem/stromal cells and stem cells derived from amniotic fluid, umbilical cord blood, adipose tissue, or urine - present the opportunity for widespread biobanking and increased access. With these increased opportunities, however, come pressing policy issues of consent, control, and justice. The imperatives to minimize risks of harm, obtain informed consent, reduce the likelihood of the therapeutic misconception, and facilitate sound translation from bench to bedside are not unique to stem cell research; their application to stem cell research and therapy nonetheless merits particular attention. Because stem cell research is both scientifically promising and ethically challenging, both the application of existing ethical frameworks and careful consideration of new ethical implications are necessary as this broad and diverse field moves forward.

  13. Effect of aging on human mesenchymal stem cell therapy in ischemic cardiomyopathy patients.

    Science.gov (United States)

    Golpanian, Samuel; El-Khorazaty, Jill; Mendizabal, Adam; DiFede, Darcy L; Suncion, Viky Y; Karantalis, Vasileios; Fishman, Joel E; Ghersin, Eduard; Balkan, Wayne; Hare, Joshua M

    2015-01-20

    The role of patient age in the efficacy of mesenchymal stem cell (MSC) therapy in ischemic cardiomyopathy (ICM) is controversial. This study sought to determine whether the therapeutic effect of culture-expanded MSCs persists, even in older subjects. Patients with ICM who received MSCs via transendocardial stem cell injection (TESI) as part of the TAC-HFT (Transendocardial Autologous Cells in Ischemic Heart Failure) (n = 19) and POSEIDON (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis) (n = 30) clinical trials were divided into 2 age groups: younger than 60 and 60 years of age and older. Functional capacity was measured by 6-min walk distance (6MWD) and quality of life using the Minnesota Living With Heart Failure Questionnaire (MLHFQ) score, measured at baseline, 6 months, and 1 year post-TESI. Various cardiac imaging parameters, including absolute scar size, were compared at baseline and 1 year post-TESI. The mean 6MWD was similar at baseline and increased at 1 year post-TESI in both groups: 48.5 ± 14.6 m (p = 0.001) for the younger and 35.9 ± 18.3 m (p = 0.038) for the older participants (p = NS between groups). The older group exhibited a significant reduction in MLHFQ score (-7.04 ± 3.54; p = 0.022), whereas the younger than 60 age group had a borderline significant reduction (-11.22 ± 5.24; p = 0.058) from baseline (p = NS between groups). Although there were significant reductions in absolute scar size from baseline to 1 year post-TESI, the effect did not differ by age. MSC therapy with TESI in ICM patients improves 6MWD and MLHFQ score and reduces myocardial infarction size. Importantly, older individuals did not have an impaired response to MSC therapy. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  14. Imaging stem cell implant for cellular-based therapies.

    Science.gov (United States)

    Lee, Zhenghong; Dennis, James E; Gerson, Stanton L

    2008-08-01

    Stem cell-based cellular therapy represents a promising outlook for regenerative medicine. Imaging techniques provide a means for noninvasive, repeated, and quantitative tracking of stem cell implant or transplant. From initial deposition to the survival, migration and differentiation of the transplant/implanted stem cells, imaging allows monitoring of the infused cells in the same live object over time. The current review briefly summarizes and compares existing imaging methods for cell labeling and imaging in animal models. Several studies performed by our group using different imaging techniques are described, with further discussion on the issues with these current imaging approaches and potential directions for future development in stem cell imaging.

  15. The Evolution of the Stem Cell Theory for Heart Failure.

    Science.gov (United States)

    Silvestre, Jean-Sébastien; Menasché, Philippe

    2015-12-01

    Various stem cell-based approaches for cardiac repair have achieved encouraging results in animal experiments, often leading to their rapid proceeding to clinical testing. However, freewheeling evolutionary developments of the stem cell theory might lead to dystopian scenarios where heterogeneous sources of therapeutic cells could promote mixed clinical outcomes in un-stratified patient populations. This review focuses on the lessons that should be learnt from the first generation of stem cell-based strategies and emphasizes the absolute requirement to better understand the basic mechanisms of stem cell biology and cardiogenesis. We will also discuss about the unexpected "big bang" in the stem cell theory, "blasting" the therapeutic cells to their unchallenged ability to release paracrine factors such as extracellular membrane vesicles. Paradoxically, the natural evolution of the stem cell theory for cardiac regeneration may end with the development of cell-free strategies with multiple cellular targets including cardiomyocytes but also other infiltrating or resident cardiac cells.

  16. Mesenchymal stem cell therapy for laryngotracheal stenosis

    DEFF Research Database (Denmark)

    Jakobsen, Kathrine Kronberg; Grønhøj, Christian; Jensen, David H

    2017-01-01

    promising results in regenerative medicine. We aimed to systematically review the literature on MSC therapy for stenosis of the conductive airways. METHODS: PubMed, EMBASE, Google Scholar and the Cochrane Library were systematically searched from January 1980-January 2017 with the purpose of identifying all...

  17. Estimation of heart-position variability in 3D-surface-image-guided deep-inspiration breath-hold radiation therapy for left-sided breast cancer

    NARCIS (Netherlands)

    Alderliesten, Tanja; Betgen, Anja; Elkhuizen, Paula H. M.; van Vliet-Vroegindeweij, Corine; Remeijer, Peter

    2013-01-01

    To investigate the heart position variability in deep-inspiration breath-hold (DIBH) radiation therapy (RT) for breast cancer when 3D surface imaging would be used for monitoring the BH depth during treatment delivery. For this purpose, surface setup data were compared with heart setup data. Twenty

  18. Effect of cardiac resynchronization therapy-defibrillator implantation on health status in patients with mild versus moderate symptoms of heart failure

    DEFF Research Database (Denmark)

    Versteeg, Henneke; van den Broek, Krista C; Theuns, Dominic A M J

    2011-01-01

    Indications for cardiac resynchronization therapy (CRT) have expanded to include patients with mild congestive heart failure (CHF) symptoms (New York Heart Association [NYHA] functional class II) because of a demonstrated morbidity reduction in this subset of patients. However, little is known...

  19. Cellular therapy after spinal cord injury using neural progenitor cells

    NARCIS (Netherlands)

    Vroemen, Maurice

    2006-01-01

    In this thesis, the possibilities and limitations of cell-based therapies after spinal cord injury are explored. Particularly, the potential of adult derived neural progenitor cell (NPC) grafts to function as a permissive substrate for axonal regeneration was investigated. It was found that syngenic

  20. Toward development of imesenchymal stem cells for immunomodulatory therapy

    NARCIS (Netherlands)

    S.F. De Witte (Samantha Fh); M. Franquesa (Marcella); C.C. Baan (Carla); M.J. Hoogduijn (Martin)

    2016-01-01

    textabstractMesenchymal stem cells (MSC) are under development as an immunomodulatory therapy. The anticipated immunomodulatory effects of MSC are broad, from direct inhibition of lymphocyte proliferation, induction of regulatory T and B cells, to resetting the immune system via a hit-and-run

  1. Heart Cells with Regenerative Potential from Pediatric Patients with End Stage Heart Failure: A Translatable Method to Enrich and Propagate

    Directory of Open Access Journals (Sweden)

    Ann Steele

    2012-01-01

    Full Text Available Background. Human cardiac-derived progenitor cells (hCPCs have shown promise in treating heart failure (HF in adults. The purpose of this study was to describe derivation of hCPCs from pediatric patients with end-stage HF. Methods. At surgery, discarded right atrial tissues (hAA were obtained from HF patients (n=25; hAA-CHF. Minced tissues were suspended in complete (serum-containing DMEM. Cells were selected for their tissue migration and expression of stem cell factor receptor (hc-kit. Characterization of hc-kitpositive cells included immunohistochemical screening with a panel of monoclonal antibodies. Results. Cells, including phase-bright cells identified as hc-kitpositive, spontaneously emigrated from hAA-CHF in suspended explant cultures (SEC after Day 7. When cocultured with tissue, emigrated hc-kitpositive cells proliferated, first as loosely attached clones and later as multicellular clusters. At Day 21~5% of cells were hc-kitpositive. Between Days 14 and 28 hc-kitpositive cells exhibited mesodermal commitment (GATA-4positive and NKX2.5positive; then after Day 28 cardiac lineages (flk-1positive, smooth muscle actinpositive, troponin-Ipositive, and myosin light chainpositive. Conclusions. C-kitpositive hCPCs can be derived from atrial tissue of pediatric patients with end-stage HF. SEC is a novel culture method for derivation of migratory hc-kitpositive cells that favors clinical translation by reducing the need for exogenously added factors to expand hCPCs in vitro.

  2. Changes in ventricular-arterial coupling during decongestive therapy in acute heart failure.

    Science.gov (United States)

    Berthelot, Emmanuelle; Bihry, Nicolas; Brault-Melin, Ophelie; Assayag, Patrick; Cohen-Solal, Alain; Chemla, Denis; Logeart, Damien

    2014-10-01

    Coupled arterial and left ventricular properties are poorly documented in acute heart failure. The aim of this prospective noninvasive study was to document early changes in ventricular-arterial coupling in patients with acutely decompensated HF (ADHF). We studied 19 patients hospitalized for ADHF (age 62 ± 15 years, NYHA class 3 or 4). Patients with shock and sustained arrhythmias were excluded. All the patients received intravenous loop diuretics, and none received intravenous vasodilators or inotropes. Ongoing chronic treatments were maintained. Echocardiography and radial artery tonometry were performed simultaneously on admission and after clinical improvement (day 4 ± 1 after admission). Classical echocardiographic parameters were measured, including stroke volume (SV). End-systolic pressure (Pes) was derived from reconstructed central aortic pressure, and arterial elastance (Ea) was calculated as Ea = Pes/SV. End-systolic LV elastance (Ees) was calculated with the single-beat method. Ventricular-arterial coupling was quantified as the Ea/Ees ratio. Following IV diuretic therapy, mean weight loss was 5 ± 2 kg (P < 0·01) and BNP fell from 1813 (median) (IQR = 1284-2342) to 694 (334-1053) pg/mL (P < 0·01). Ea fell by 29%, from 2·46 (2·05-2·86) to 1·78 (1·55-2·00) mmHg/mL (P < 0·01), while Ees remained unchanged (1·28 (1·05-1·52) to 1·13 (0·92-1·34) mmHg/mL). The Ea/Ees ratio therefore fell, from 2·13 (1·70-2·56) to 1·81 (1·56-2·08) (P < 0·02). An early improvement in ventricular-arterial coupling was observed after diuretic-related decongestive therapy in ADHF patients and was related to a decrease in effective arterial elastance rather than to change in LV contractility. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

  3. Heart rate is associated with mortality in patients undergoing continuous renal replacement therapy

    Directory of Open Access Journals (Sweden)

    Soojin Lee

    2017-09-01

    Full Text Available Background: Heart rate (HR is an essential vital sign based on the finding that HR beyond its normal range is associated with several conditions or diseases, including high mortality in several clinical settings. Nevertheless, the clinical implications of HR remain unresolved in patients undergoing continuous renal replacement therapy (CRRT. Methods: This retrospective cohort study included 828 patients who underwent CRRT due to acute kidney injury between 2010 and 2014. HR and other baseline parameters at the time of CRRT initiation were retrieved. The odds ratio (OR of 30-day mortality was calculated using a multivariate logistic model. Results: CRRT significantly lowered the HR of patients such that the pre- and post-CRRT HRs (average 6 hours were 107 beats/min and 103 beats/min, respectively (P < 0.001. When we explored the relationship with 30-day mortality, only HR at the time of CRRT initiation, but not pre- or post-CRRT HR, had a significant relationship with mortality outcome. Based on this result, we divided patients into quartiles of HR at the time of CRRT initiation. Mortality OR in the 4th quartile HR group was 2.6 (1.78–3.92 compared with the 1st quartile HR group. This relationship remained consistent despite adjusting for 28 baseline covariates: OR, 1.7 (1.09–2.76; P = 0.020. However, HR was not associated with the weaning rate from CRRT. Conclusion: High HR at the time of CRRT initiation is subsequently related with high mortality. These results can be a basis for a future predictive model of CRRT-related mortality.

  4. Underutilization of high-intensity statin therapy after hospitalization for coronary heart disease.

    Science.gov (United States)

    Rosenson, Robert S; Kent, Shia T; Brown, Todd M; Farkouh, Michael E; Levitan, Emily B; Yun, Huifeng; Sharma, Pradeep; Safford, Monika M; Kilgore, Meredith; Muntner, Paul; Bittner, Vera

    2015-01-27

    National guidelines recommend use of high-intensity statins after hospitalization for coronary heart disease (CHD) events. This study sought to estimate the proportion of Medicare beneficiaries filling prescriptions for high-intensity statins after hospital discharge for a CHD event and to analyze whether statin intensity before hospitalization is associated with statin intensity after discharge. We conducted a retrospective cohort study using a 5% random sample of Medicare beneficiaries between 65 and 74 years old. Beneficiaries were included in the analysis if they filled a statin prescription after a CHD event (myocardial infarction or coronary revascularization) in 2007, 2008, or 2009. High-intensity statins included atorvastatin 40 to 80 mg, rosuvastatin 20 to 40 mg, and simvastatin 80 mg. Among 8,762 Medicare beneficiaries filling a statin prescription after a CHD event, 27% of first post-discharge fills were for a high-intensity statin. The percent filling a high-intensity statin post-discharge was 23.1%, 9.4%, and 80.7%, for beneficiaries not taking statins pre-hospitalization, taking low/moderate-intensity statins, and taking high-intensity statins before their CHD event, respectively. Compared with beneficiaries not on statin therapy pre-hospitalization, multivariable adjusted risk ratios for filling a high-intensity statin were 4.01 (3.58-4.49) and 0.45 (0.40-0.52) for participants taking high-intensity and low/moderate-intensity statins before their CHD event, respectively. Only 11.5% of beneficiaries whose first post-discharge statin fill was for a low/moderate-intensity statin filled a high-intensity statin within 365 days of discharge. The majority of Medicare beneficiaries do not fill high-intensity statins after hospitalization for CHD. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  5. Angiomyeloproliferative Lesions Following Autologous Stem Cell Therapy

    OpenAIRE

    Thirabanjasak, Duangpen; Tantiwongse, Kavirach; Thorner, Paul Scott

    2010-01-01

    Some reports suggest that autologous hematopoietic stem cell transplantation holds potential for treatment of renal diseases such as lupus nephritis, but the safety of delivering various stem cell types (hematopoietic, mesenchymal, and endothelial precursors) is not well established. Here, we report a case of lupus nephritis treated by direct renal injection of autologous stem cells recovered from peripheral blood. The patient developed masses at the sites of injection and hematuria. We suspe...

  6. Stem Cell Therapies for Treatment of Liver Disease

    Directory of Open Access Journals (Sweden)

    Clara Nicolas

    2016-01-01

    Full Text Available Cell therapy is an emerging form of treatment for several liver diseases, but is limited by the availability of donor livers. Stem cells hold promise as an alternative to the use of primary hepatocytes. We performed an exhaustive review of the literature, with a focus on the latest studies involving the use of stem cells for the treatment of liver disease. Stem cells can be harvested from a number of sources, or can be generated from somatic cells to create induced pluripotent stem cells (iPSCs. Different cell lines have been used experimentally to support liver function and treat inherited metabolic disorders, acute liver failure, cirrhosis, liver cancer, and small-for-size liver transplantations. Cell-based therapeutics may involve gene therapy, cell transplantation, bioartificial liver devices, or bioengineered organs. Research in this field is still very active. Stem cell therapy may, in the future, be used as a bridge to either liver transplantation or endogenous liver regeneration, but efficient differentiation and production protocols must be developed and safety must be demonstrated before it can be applied to clinical practice.

  7. Mesenchymal Stem Cell Therapy in Diabetes Mellitus: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Nagwa El-Badri

    2013-01-01

    Full Text Available Advanced type 2 diabetes mellitus is associated with significant morbidity and mortality due to cardiovascular, nervous, and renal complications. Attempts to cure diabetes mellitus using islet transplantation have been successful in providing a source for insulin secreting cells. However, limited donors, graft rejection, the need for continued immune suppression, and exhaustion of the donor cell pool prompted the search for a more sustained source of insulin secreting cells. Stem cell therapy is a promising alternative for islet transplantation in type 2 diabetic patients who fail to control hyperglycemia even with insulin injection. Autologous stem cell transplantation may provide the best outcome for those patients, since autologous cells are readily available and do not entail prolonged hospital stays or sustained immunotoxic therapy. Among autologous adult stem cells, mesenchymal stem cells (MSCs therapy has been applied with varying degrees of success in both animal models and in clinical trials. This review will focus on the advantages of MSCs over other types of stem cells and the possible mechanisms by which MSCs transplant restores normoglycemia in type 2 diabetic patients. Sources of MSCs including autologous cells from diabetic patients and the use of various differentiation protocols in relation to best transplant outcome will be discussed.

  8. Comparison of Ambulatory, High-Dose, Intravenous Diuretic Therapy to Standard Hospitalization and Diuretic Therapy for Treatment of Acute Decompensated Heart Failure.

    Science.gov (United States)

    Buckley, Leo F; Seoane-Vazquez, Enrique; Cheng, Judy W M; Aldemerdash, Ahmed; Cooper, Irene M; Matta, Lina; Medina, Danika S; Mehra, Mandeep R; Navarro-Velez, Kristina; Shea, Elaine L; Weintraub, Joanne R; Stevenson, Lynne W; Desai, Akshay S

    2016-11-01

    Innovative treatment strategies for decompensated heart failure (HF) are required to achieve cost savings and improvements in outcomes. We developed a decision analytic model from a hospital perspective to compare 2 strategies for the treatment of decompensated HF, ambulatory diuretic infusion therapy, and hospitalization (standard care), with respect to total HF hospitalizations and costs. The ambulatory diuretic therapy strategy included outpatient treatment with high doses of intravenous loop diuretics in a specialized HF unit whereas standard care included hospitalization for intravenous loop diuretic therapy. Model probabilities were derived from the outcomes of patients who were treated for decompensated HF at Brigham and Women's Hospital (Boston, MA). Costs were based on Centers for Medicare and Medicaid reimbursement and the available reports. Based on a sample of patients treated at our institution, the ambulatory diuretic therapy strategy was estimated to achieve a significant reduction in total HF hospitalizations compared with standard care (relative reduction 58.3%). Under the base case assumptions, the total cost of the ambulatory diuretic therapy strategy was $6,078 per decompensation episode per 90 days compared with $12,175 per 90 days with standard care, for a savings of $6,097. The cost savings associated with the ambulatory diuretic strategy were robust against variation up to 50% in costs of ambulatory diuretic therapy and the likelihood of posttreatment hospitalization. An exploratory analysis suggests that ambulatory diuretic therapy is likely to remain cost saving over the long-term. In conclusion, this decision analytic model demonstrates that ambulatory diuretic therapy is likely to be cost saving compared with hospitalization for the treatment of decompensated HF from a hospital perspective. These results suggest that implementation of outpatient HF units that provide ambulatory diuretic therapy to well-selected subgroup of patients may

  9. The comparative effects of long-term carvedilol versus bisoprolol therapy on QT dispersion in patients with chronic heart failure.

    Science.gov (United States)

    Aygul, Nazif; Ozdemir, Kurtulus; Duzenli, Mehmet Akif; Aygul, Meryem Ulku

    2009-01-01

    Carvedilol and bisoprolol reduce QT dispersion (QTD) in chronic heart failure (CHF). However, it is unclear whether there is a difference between the effects of the two drugs. The aim of the present study was to compare the long-term effects of carvedilol and bisoprolol on QTD in patients with CHF. Eighty-one patients with CHF with no previous beta-blocker therapy were included in this prospective study. The patients were randomly allocated to carvedilol or bisoprolol therapy. Left ventricular ejection fraction (LVEF), heart rate (HR), QTD, and corrected QTD (QTcD) were calculated at baseline and at the 6th month of therapy. In comparison to baseline values in both therapy groups, LVEF was significantly improved, and a statistically significant decrease was found in HR (carvedilol from 76 +/- 12 to 65 +/- 10 beats/min, p < 0.001; bisoprolol from 78 +/- 13 to 65 +/- 8 beats/min, p < 0.001) and QTcD (carvedilol from 85 +/- 28 to 65 +/- 22 ms, p < 0.001; bisoprolol from 83 +/- 22 to 61 +/- 20 ms, p < 0.001). In our study, carvedilol and bisoprolol were found to have similar effects on LVEF, HR, and QTcD. Carvedilol and bisoprolol decrease HR and QTcD in patients with CHF, and there is no meaningful difference between the two beta-blockers as regards their effects on these parameters. Copyright 2008 S. Karger AG, Basel.

  10. Current perspectives on imaging cardiac stem cell therapy.

    Science.gov (United States)

    Wu, Joseph C; Abraham, M Roselle; Kraitchman, Dara L

    2010-05-01

    Molecular imaging is a new discipline that makes possible the noninvasive visualization of cellular and molecular processes in living subjects. In the field of cardiovascular regenerative therapy, imaging cell fate after transplantation is a high priority in both basic research and clinical translation. For cell-based therapy to truly succeed, we must be able to track the locations of delivered cells, the duration of cell survival, and any potential adverse effects. The insights gathered from basic research imaging studies will yield valuable insights into better designs for clinical trials. This review highlights the different types of stem cells used for cardiovascular repair, the development of various imaging modalities to track their fate in vivo, and the challenges of clinical translation of cardiac stem cell imaging in the future.

  11. CAR-T Cell Therapies From the Transfusion Medicine Perspective.

    Science.gov (United States)

    Fesnak, Andrew; Lin, ChieYu; Siegel, Don L; Maus, Marcela V

    2016-07-01

    The use of chimeric antigen receptor (CAR)-T cell therapy for the treatment of hematologic malignancies has generated significant excitement over the last several years. From a transfusion medicine perspective, the implementation of CAR-T therapy as a potential mainstay treatment for not only hematologic but also solid-organ malignancies represents a significant opportunity for growth and expansion. In this review, we will describe the rationale for the development of genetically redirected T cells as a cancer therapeutic, the different elements that are required to engineer these cells, as well as an overview of the process by which patient cells are harvested and processed to create and subsequently validate CAR-T cells. Finally, we will briefly describe some of the toxicities and clinical efficacy of CAR-T cells in the setting of patients with advanced malignancy. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Mesenchymal stem cells: cell biology and potential use in therapy

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Kristiansen, Malthe; Abdallah, Basem M

    2004-01-01

    Mesenchymal stem cells are clonogenic, non-haematopoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages e.g. osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages e.g. neuronal-like cells. Several methods a...

  13. Probing early heart development to instruct stem cell differentiation strategies

    National Research Council Canada - National Science Library

    Calderon, Damelys; Bardot, Evan; Dubois, Nicole

    2016-01-01

    .... These discoveries are driven by the need to answer long‐standing questions regarding the origin of the earliest cells specified to the cardiac lineage, the differentiation potential of distinct cardiac progenitor cells, and, very importantly, the molecular...

  14. Duchenne muscular dystrophy: current cell therapies

    OpenAIRE

    Sienkiewicz, Dorota; Kulak, Wojciech; Okurowska-Zawada, Bożena; Paszko-Patej, Grażyna; Kawnik, Katarzyna

    2015-01-01

    Duchenne muscular dystrophy is a genetically determined X-linked disease and the most common, progressive pediatric muscle disorder. For decades, research has been conducted to find an effective therapy. This review presents current therapeutic methods for Duchenne muscular dystrophy, based on scientific articles in English published mainly in the period 2000 to 2014. We used the PubMed database to identify and review the most important studies. An analysis of contemporary studies of stem cel...

  15. Stem-Cell Based Therapies for Epidermolysis Bullosa

    Science.gov (United States)

    2014-10-01

    100) (Life Technologies), B27 supplement (50) (Life Technologies), 50 μg/mL ascorbic acid , 0.05 % bovine serum albumin (BSA), 50U/mLpenicillin...EB), a group of rare inherited skin blistering diseases. To accomplish this goal, we are proposing to develop stem-cell based therapies for EB using...autologous induced pluripotent stem cells (iPSCs) derived from skin cells harvested from the same EB patient. During the second year of funding, we

  16. Mycoplasma Removal from Cell Culture Using Antimicrobial Photodynamic Therapy

    OpenAIRE

    Hasebe, Akira; Ishikawa, Isao; Shamsul, Haque M.; Ohtani, Makoto; Segawa, Taku; Saeki, Ayumi; Tanizume, Naoho; Oouchi, Manabu; Okagami, Yoshihide; Okano, Teruo; Shibata, Ken-ichiro

    2013-01-01

    Objective: The objective of this research was to determine the effectiveness of antimicrobial photodynamic therapy (aPDT) in the removal of mycoplasmas from contaminated cells. Background data: Mycoplasmas often contaminate cell cultures. The cell-contaminating mycoplasmas are removed by antibiotics, but the use of antibiotics usually induces antibiotic-resistant bacteria. aPDT is expected to be a possible alternative to antibiotic treatments for suppressing infections. Materials and Methods:...

  17. Cell therapy to remove excess copper in Wilson's disease.

    Science.gov (United States)

    Gupta, Sanjeev

    2014-05-01

    To achieve permanent correction of Wilson's disease by a cell therapy approach, replacement of diseased hepatocytes with healthy hepatocytes is desirable. There is a physiological requirement for hepatic ATP7B-dependent copper (Cu) transport in bile, which is deficient in Wilson's disease, producing progressive Cu accumulation in the liver or brain with organ damage. The ability to repopulate the liver with healthy hepatocytes raises the possibility of cell therapy in Wilson's disease. Therapeutic principles included reconstitution of bile canalicular network as well as proliferation in transplanted hepatocytes, despite toxic amounts of Cu in the liver. Nonetheless, cell therapy studies in animal models elicited major differences in the mechanisms driving liver repopulation with transplanted hepatocytes in Wilson's disease versus nondiseased settings. Recently, noninvasive imaging was developed to demonstrate Cu removal from the liver, including after cell therapy in Wilson's disease. Such developments will help advance cell/gene therapy approaches, particularly by offering roadmaps for clinical trials in people with Wilson's disease. © 2014 New York Academy of Sciences.

  18. Chimeric antigen receptor engineered stem cells: a novel HIV therapy.

    Science.gov (United States)

    Zhen, Anjie; Carrillo, Mayra A; Kitchen, Scott G

    2017-03-01

    Despite the success of combination antiretroviral therapy (cART) for suppressing HIV and improving patients' quality of life, HIV persists in cART-treated patients and remains an incurable disease. Financial burdens and health consequences of lifelong cART treatment call for novel HIV therapies that result in a permanent cure. Cellular immunity is central in controlling HIV replication. However, HIV adopts numerous strategies to evade immune surveillance. Engineered immunity via genetic manipulation could offer a functional cure by generating cells that have enhanced antiviral activity and are resistant to HIV infection. Recently, encouraging reports from several human clinical trials using an anti-CD19 chimeric antigen receptor (CAR) modified T-cell therapy for treating B-cell malignancies have provided valuable insights and generated remarkable enthusiasm in engineered T-cell therapy. In this review, we discuss the development of HIV-specific chimeric antigen receptors and the use of stem cell based therapies to generate lifelong anti-HIV immunity.

  19. Stem Cell-based Therapies for Sepsis.

    Science.gov (United States)

    Keane, Colm; Jerkic, Mirjana; Laffey, John G

    2017-12-01

    Sepsis is a life-threatening syndrome resulting in shock and organ dysfunction stemming from a microbial infection. Sepsis has a mortality of 40% and is implicated in half of all in-hospital deaths. The host immune response to microbial infection is critical, with early-phase sepsis characterized by a hyperinflammatory immune response, whereas the later phase of sepsis is often complicated by suppression. Sepsis has no treatment, and management remains supportive.Stem cells constitute exciting potential therapeutic agents for sepsis. In this review, we examine the rationale for stem cells in sepsis, focusing on mesenchymal stem/stromal cells, which currently demonstrate the greatest therapeutic promise. We examine the preclinical evidence base and evaluate potential mechanisms of action of these cells that are important in the setting of sepsis. We discuss early-phase clinical trials and critically appraise translational barriers to the use of mesenchymal stem/stromal cells in patients with sepsis.

  20. Embodied Revelation: A Classic Grounded Theory of Heart Failure Patient Decision Making Surrounding Primary Prevention Implantable Cardioverter Defibrillator Therapy

    Directory of Open Access Journals (Sweden)

    Vera Barton-Caro Ph.D.,

    2015-12-01

    Full Text Available The purpose of this classic grounded theory study was to explain the complex decision making process of heart failure (HF patients considering primary prevention implantable cardioverter defibrillator (ICD therapy. Sudden cardiac death (SCD is the leading cause of death for people with HF as well as the primary cause of death in the United States (US. ICDs represent the standard of care as the only effective therapy for primary prevention of SCD. However, a significant proportion of qualifying HF patients declines this invasive, yet life-saving device. The grounded theory is of Embodied revelation. The threat of SCD for ICD candidates consists of four stages: living in conscious denial, heightening of awareness, sanctioning ICD therapy, and living in new assurance. The first stage ends abruptly with the critical juncture of grasping the threat of SCD. This grounded theory has implications for research, nursing and medical practice, as well as bioethical considerations.

  1. Escaping Antiangiogenic Therapy: Strategies Employed by Cancer Cells

    Directory of Open Access Journals (Sweden)

    Mauricio P. Pinto

    2016-09-01

    Full Text Available Tumor angiogenesis is widely recognized as one of the “hallmarks of cancer”. Consequently, during the last decades the development and testing of commercial angiogenic inhibitors has been a central focus for both basic and clinical cancer research. While antiangiogenic drugs are now incorporated into standard clinical practice, as with all cancer therapies, tumors can eventually become resistant by employing a variety of strategies to receive nutrients and oxygen in the event of therapeutic assault. Herein, we concentrate and review in detail three of the principal mechanisms of antiangiogenic therapy escape: (1 upregulation of compensatory/alternative pathways for angiogenesis; (2 vasculogenic mimicry; and (3 vessel co-option. We suggest that an understanding of how a cancer cell adapts to antiangiogenic therapy may also parallel the mechanisms employed in the bourgeoning tumor and isolated metastatic cells delivering responsible for residual disease. Finally, we speculate on strategies to adapt antiangiogenic therapy for future clinical uses.

  2. How to Improve the Survival of Transplanted Mesenchymal Stem Cell in Ischemic Heart?

    Directory of Open Access Journals (Sweden)

    Liangpeng Li

    2016-01-01

    Full Text Available Mesenchymal stem cell (MSC is an intensely studied stem cell type applied for cardiac repair. For decades, the preclinical researches on animal model and clinical trials have suggested that MSC transplantation exerts therapeutic effect on ischemic heart disease. However, there remain major limitations to be overcome, one of which is the very low survival rate after transplantation in heart tissue. Various strategies have been tried to improve the MSC survival, and many of them showed promising results. In this review, we analyzed the studies in recent years to summarize the methods, effects, and mechanisms of the new strategies to address this question.

  3. Stem Cell Therapy: A New Treatment for Burns?

    Directory of Open Access Journals (Sweden)

    Gerd G. Gauglitz

    2011-10-01

    Full Text Available Stem cell therapy has emerged as a promising new approach in almost every medicine specialty. This vast, heterogeneous family of cells are now both naturally (embryonic and adult stem cells or artificially obtained (induced pluripotent stem cells or iPSCs and their fates have become increasingly controllable, thanks to ongoing research in this passionate new field. We are at the beginning of a new era in medicine, with multiple applications for stem cell therapy, not only as a monotherapy, but also as an adjunct to other strategies, such as organ transplantation or standard drug treatment. Regrettably, serious preclinical concerns remain and differentiation, cell fusion, senescence and signalling crosstalk with growth factors and biomaterials are still challenges for this promising multidisciplinary therapeutic modality. Severe burns have several indications for stem cell therapy, including enhancement of wound healing, replacement of damaged skin and perfect skin regeneration – incorporating skin appendages and reduced fibrosis –, as well as systemic effects, such as inflammation, hypermetabolism and immunosuppression. The aim of this review is to describe well established characteristics of stem cells and to delineate new advances in the stem cell field, in the context of burn injury and wound healing.

  4. Statin therapy reduces inappropriate shock in non-ischemic patients with mild heart failure

    DEFF Research Database (Denmark)

    Ruwald, Anne-Christine H.; Zareba, Wojciech; Jons, Christian

    2013-01-01

    therapy in patients with and without diabetes mellitus. Diabetes mellitus was associated with lower risk of inappropriate therapy but higher risk of appropriate therapy. Appropriate and inappropriate ICD therapy was associated with increased mortality in diabetic patients. CLINICAL TRIAL REGISTRATION: URL......: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00947310....

  5. Heart failure following blood cancer therapy in pediatric and adult populations.

    Science.gov (United States)

    Franzon, Julie; Berry, Narelle M; Ullah, Shahid; Versace, Vincent L; McCarthy, Alexandra L; Atherton, John; Roder, David; Koczwara, Bogda; Coghlan, Douglas; Clark, Robyn A

    2017-10-12

    The link between chemotherapy treatment and cardiotoxicity is well established, particularly for adults with blood cancers. However, it is less clear for children. This analysis aimed to compare the trajectory and mortality of children and adults who received chemotherapy for blood cancers and were subsequently hospitalized for heart failure. Linked data from the Queensland Cancer Registry, Death Registry and Hospital Administration records for initial chemotherapy and later heart failure were reviewed (1996-2009). Of all identified blood cancer patients (N = 23 434), 8339 received chemotherapy, including 817 children (aged ≤18 years at time of cancer diagnosis) and 7522 adults. Time-varying Cox proportional hazards regression models were used to compare the characteristics and survival between the two groups. Of those who were subsequently hospitalized for heart failure, 70% of children and 46% of adults had the index admission within 12 months of their cancer diagnosis. Of these, 53% of the pediatric heart failure population and 71% of the adult heart failure population died within the study period. Following adjustment for age, sex and chemotherapy admissions, children with heart failure had an increased mortality risk compared to their non-heart failure counterparts, a difference which was much greater than that between the adult groups. The impact of heart failure on children previously treated for blood cancer is more severe than for adults, with earlier morbidity and greater mortality. Improved strategies are needed for the prevention and management of cardiotoxicity in this population. © 2017 John Wiley & Sons Australia, Ltd.

  6. Resynchronization therapy after congenital heart surgery to improve left ventricular function

    NARCIS (Netherlands)

    Roofthooft, Marcus T. R.; Blom, Nico A.; Rijlaarsdam, Marry E. B.; Bökenkamp, Regina; Ottenkamp, Jaap; Schalij, Martin J.; Bax, Jeroen J.; Hazekamp, Mark G.

    2003-01-01

    This report describes the mid-term beneficial hemodynamic effect of biventricular pacing in an infant with congestive heart failure after congenital heart surgery, due to resynchronization of the left and right ventricle, optimization of the AV delay, and (partial) correction of the LV dyssynchrony

  7. Drug therapy in heart failure : studies on prescribing, drug induced problems and compliance

    NARCIS (Netherlands)

    Bouvy, M.L.

    2002-01-01

    Due to the ageing of the population and increased survival of patients with acute coronary artery disease, an ‘epidemic’ of heart failure is emerging, illustrated by increasing rates of hospitalisations for heart failure and resulting in a considerable increase in the cost of care for these

  8. Stem cell therapy - Hope and scope in pediatric surgery

    Directory of Open Access Journals (Sweden)

    Gupta Devendra

    2005-01-01

    Full Text Available A stem cell is an undifferentiated cell in the body with undetermined function capable of forming various tissues under definite signals received from the body. Stem cell research in animals using embryonal stem cells has been an ongoing program in the west with fruitful results. However, only limited information is available with the use of stem cells in human beings. Of the various sources of stem cells, umbilical cord blood stem cell research has shown potential for future treatment in Alzheimer′s, Parkinson′s, heart attack, stroke and spinal cord injuries. Human trials have been done in diseases like spinal cord injury and chronic liver cirrhosis. Cord blood stem cells have already been effectively used in the treatment of sickle cell, leukemia, non-Hodgkin′s lymphoma and some other cancers, life threatening anemias and auto-immune diseases. Current challenges with the use of stem cells in clinical practice include the provisions to direct the differentiation of embryonic stem cells into specialized cell populations, and also devise ways to guard their development or proliferation once placed in vivo. Only further research and its clinical application will solve the many unanswered queries.

  9. Tracking fusion of human mesenchymal stem cells after transplantation to the heart.

    Science.gov (United States)

    Freeman, Brian T; Kouris, Nicholas A; Ogle, Brenda M

    2015-06-01

    Evidence suggests that transplanted mesenchymal stem cells (MSCs) can aid recovery of damaged myocardium caused by myocardial infarction. One possible mechanism for MSC-mediated recovery is reprogramming after cell fusion between transplanted MSCs and recipient cardiac cells. We used a Cre/LoxP-based luciferase reporter system coupled to biophotonic imaging to detect fusion of transplanted human pluripotent stem cell-derived MSCs to cells of organs of living mice. Human MSCs, with transient expression of a viral fusogen, were delivered to the murine heart via a collagen patch. At 2 days and 1 week later, living mice were probed for bioluminescence indicative of cell fusion. Cell fusion was detected at the site of delivery (heart) and in distal tissues (i.e., stomach, small intestine, liver). Fusion was confirmed at the cellular scale via fluorescence in situ hybridization for human-specific and mouse-specific centromeres. Human cells in organs distal to the heart were typically located near the vasculature, suggesting MSCs and perhaps MSC fusion products have the ability to migrate via the circulatory system to distal organs and engraft with local cells. The present study reveals previously unknown migratory patterns of delivered human MSCs and associated fusion products in the healthy murine heart. The study also sets the stage for follow-on studies to determine the functional effects of cell fusion in a model of myocardial damage or disease. Mesenchymal stem cells (MSCs) are transplanted to the heart, cartilage, and other tissues to recover lost function or at least limit overactive immune responses. Analysis of tissues after MSC transplantation shows evidence of fusion between MSCs and the cells of the recipient. To date, the biologic implications of cell fusion remain unclear. A newly developed in vivo tracking system was used to identify MSC fusion products in living mice. The migratory patterns of fusion products were determined both in the target organ (i

  10. SERCA2a gene therapy restores microRNA-1 expression in heart failure via an Akt/FoxO3A-dependent pathway

    OpenAIRE

    Kumarswamy, R.; Lyon, AR; Volkmann, I.; Mills, AM; Bretthauer, J; Pahuja, A.; Geers-Knoerr, C.; Kraft, T.; Hajjar, RJ; Macleod, KT; Harding, SE; Thum, T.

    2012-01-01

    Aims Impaired myocardial sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) activity is a hallmark of failing hearts, and SERCA2a gene therapy improves cardiac function in animals and patients with heart failure (HF). Deregulation of microRNAs has been demonstrated in HF pathophysiology. We studied the effects of therapeutic AAV9.SERCA2a gene therapy on cardiac miRNome expression and focused on regulation, expression, and function of miR-1 in reverse remodelled failing hearts. Methods and res...

  11. The role of stem cells in glioma progression and therapy

    Directory of Open Access Journals (Sweden)

    Mateja Obrez

    2013-02-01

    Full Text Available The concepts of tumour origin and stochastic nature of carcinogenesis are being challenged today by hierarchical models that predict the existence of cancer stem cells (CSCs, which are postulated as unique cell population capable of infinite self renewal, multilineage differentiation and having a higher resistance to conventional cancer therapy thus facilitating malignant growth and therapy resistance. Accordingly, successful treatment of adult brain tumour–glioma and its most malignant stage–glioblastoma multiforme (GBM, would require the elimination of CSCs to avoid tumour relapse. Yet, with available therapy (i.e. surgery in GBMs this cannot be achieved, due to infiltrative growth of a subpopluation of GBM cells with highly expressed migratory genes (migratome into the normal brain tissue.Besides CSCs – a proven prerequisite for tumour development and progression, tumour bulk mass also comprises haematopoietic stem cells, endothelial progenitor cells and mesenchymal stem cells (MSCs. The role of these other types of stem cell was shown to largely depend on the tumour microenvironment, where their contradictory anti-tumour action was evidenced. Yet, the exact mechanisms and MSC’s role in cell-mediated modulation of tumour behaviour via paracrine and direct interactions with GBM (stem cells still remain unknown. Nevertheless these stem cells, particularly MSCs, may represent novel therapeutic vectors for enhanced target-site delivery of chemotherapeutics, which are urgently needed to improve efficiency of current glioma treatment. So far, cell therapy using MSCs appears promising, due to MSC’s selective tumour tropism and their immuno-modulatory potential regarding treatment of GBM, which will be discussed in this review.

  12. Protein Phosphatase Inhibitor-1 Gene Therapy in a Swine Model of Nonischemic Heart Failure.

    Science.gov (United States)

    Watanabe, Shin; Ishikawa, Kiyotake; Fish, Kenneth; Oh, Jae Gyun; Motloch, Lukas J; Kohlbrenner, Erik; Lee, Philyoung; Xie, Chaoqin; Lee, Ahyoung; Liang, Lifan; Kho, Changwon; Leonardson, Lauren; McIntyre, Maritza; Wilson, Scott; Samulski, R Jude; Kranias, Evangelia G; Weber, Thomas; Akar, Fadi G; Hajjar, Roger J

    2017-10-03

    Increased protein phosphatase-1 in heart failure (HF) induces molecular changes deleterious to the cardiac cell. Inhibiting protein phosphatase-1 through the overexpression of a constitutively active inhibitor-1 (I-1c) has been shown to reverse cardiac dysfunction in a model of ischemic HF. This study sought to determine the therapeutic efficacy of a re-engineered adenoassociated viral vector carrying I-1c (BNP116.I-1c) in a preclinical model of nonischemic HF, and to assess thoroughly the safety of BNP116.I-1c gene therapy. Volume-overload HF was created in Yorkshire swine by inducing severe mitral regurgitation. One month after mitral regurgitation induction, pigs were randomized to intracoronary delivery of either BNP116.I-1c (n = 6) or saline (n = 7). Therapeutic efficacy and safety were evaluated 2 months after gene delivery. Additionally, 24 naive pigs received different doses of BNP116.I-1c for safety evaluation. At 1 month after mitral regurgitation induction, pigs developed HF as evidenced by increased left ventricular end-diastolic pressure and left ventricular volume indexes. Treatment with BNP116.I-1c resulted in improved left ventricular ejection fraction (-5.9 ± 4.2% vs. 5.5 ± 4.0%; p pigs also exhibited a significant increase in left atrial ejection fraction at 2 months after gene delivery (-4.3 ± 3.1% vs. 7.5 ± 3.1%; p = 0.02). In vitro I-1c gene transfer in isolated left atrial myocytes from both pigs and rats increased calcium transient amplitude, consistent with its positive impact on left atrial contraction. We found no evidence of adverse electrical remodeling, arrhythmogenicity, activation of a cellular immune response, or off-target organ damage by BNP116.I-1c gene therapy in pigs. Intracoronary delivery of BNP116.I-1c was safe and improved contractility of the left ventricle and atrium in a large animal model of nonischemic HF. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights

  13. Effects of music therapy on subjective sensations and heart rate variability in treated cancer survivors: a pilot study.

    Science.gov (United States)

    Chuang, Chih-Yuan; Han, Wei-Ru; Li, Pei-Chun; Young, Shuenn-Tsong

    2010-10-01

    Data on the effects of music therapy on subjective sensations and the physiological parameters of heart rate variability (HRV) in treated cancer survivors are scarce. The aim of this study was to determine whether or not music therapy affects the sensations of fatigue, comfort, and relaxation in cancer survivors, and affects the activities of the sympathetic and parasympathetic nervous systems as indicated by HRV parameters. Twenty-three patients aged 30-67 years and with cancer that had been treated at least 6 months previously received music therapy for about 2h, which included singing, listening to music, learning the recorder, and performing music. Subjective sensations and electrocardiogram were recorded before and after the music therapy. The low-frequency and high-frequency components of HRV were assessed by the frequency analysis of sequential R wave to R wave intervals of electrocardiogram obtained from 5-min recordings. Subjective sensations were quantitatively assessed using a visual analog mood scale. Two hours of music therapy significantly increased relaxation sensations and significantly decreased fatigue sensation in treated cancer survivors. Moreover, the HRV parameters showed that parasympathetic nervous system activity increased and sympathetic nervous system activity decreased. This study provides preliminary evidence that music therapy may be clinically useful for promoting relaxation sensation and increasing parasympathetic nervous system activity in treated cancer survivors. Copyright © 2010. Published by Elsevier Ltd.

  14. Clinical application of cell, gene and tissue therapies in Spain.

    Science.gov (United States)

    Gálvez-Martín, P; Ruiz, A; Clares, B

    2017-10-12

    Scientific and technical advances in the areas of biomedicine and regenerative medicine have enabled the development of new treatments known as "advanced therapies", which encompass cell therapy, genetics and tissue engineering. The biologic products that can be manufactured from these elements are classified from the standpoint of the Spanish Agency of Medication and Health Products in advanced drug therapies, blood products and transplants. This review seeks to provide scientific and administrative information for clinicians on the use of these biologic resources. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  15. Change in cholesterol absorption and synthesis markers in patients with coronary heart disease after combination therapy with simvastatin plus ezetimibe.

    Science.gov (United States)

    Zhang, Tao; Wu, Wen-feng; Liu, Yang; Wang, Qi-hui; Wang, Lü-ya; Mi, Shu-hua

    2013-01-01

    Statins and ezetimibe have been reported to change the balance of cholesterol metabolism, but few studies have been performed on Chinese patients. The aim of this study was to evaluate changes in cholesterol metabolism markers in patients with coronary heart disease. Forty-five patients with coronary heart disease were treated with 20 mg/d of simvastatin for four weeks. Subjects were then divided into two different therapy groups according to whether they reached the target values for total cholesterol and low density lipoprotein cholesterol level. Patients who reached the target values remained on simvastatin and those who did not reach the target values took a combination of simvastatin plus 10 mg/d ezetimibe until the 12th week. The concentrations of cholesterol synthesis markers (lathosterol and desmosterol) and absorption markers (campesterol and sitosterol) were measured on the 1st, 4th, and 12th week of the study by gas chromatography. After treatment with simvastatin for four weeks, the levels of total cholesterol and low density lipoprotein cholesterol decreased significantly compared to levels measured during the 1st week (P heart disease patients with high cholesterol synthesis at baseline might gain a greater benefit from simvastatin treatment. Combination therapy with simvastatin plus ezetimibe in patients with low cholesterol synthesis at baseline might increase the success rate of lipid-lowering through decreasing the absorption of cholesterol.

  16. Rationale and Design of the Left Atrial Pressure Monitoring to Optimize Heart Failure Therapy Study (LAPTOP-HF).

    Science.gov (United States)

    Maurer, Mathew S; Adamson, Philip B; Costanzo, Maria Rosa; Eigler, Neal; Gilbert, Joanne; Gold, Michael R; Klapholz, Marc; Saxon, Leslie A; Singh, Jagmeet P; Troughton, Richard; Abraham, William T

    2015-06-01

    Daily measurements of left atrial pressure (LAP) may be useful for guiding adjustments in medical therapy that prevent clinical decompensation in patients with severe heart failure (HF). LAPTOP-HF is a prospective, multicenter, randomized, controlled clinical trial in ambulatory patients with advanced heart failure in which the safety and clinical effectiveness of a physician-directed patient self-management therapeutic strategy based on LAP measured twice daily by means of an implantable sensor will be compared with a control group receiving optimal medical therapy. The trial will enroll up to 730 patients with New York Heart Association functional class III symptoms and either a hospitalization for HF during the previous 12 months or an elevated B-type natriuretic peptide level, regardless of ejection fraction, at up to 75 investigational centers. Randomization to the treatment group or control group will be at a 1:1 ratio in 3 strata based on the ejection fraction (EF > or ≤35%) and the presence of a de novo CRT device indication. LAPTOP-HF will provide essential information about the role of implantable LAP monitoring in conjunction with a new HF treatment paradigm across the spectrum of HF patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. The Evolution of the Stem Cell Theory for Heart Failure

    Directory of Open Access Journals (Sweden)

    Jean-Sébastien Silvestre

    2015-12-01

    Full Text Available Various stem cell-based approaches for cardiac repair have achieved encouraging results in animal experiments, often leading to their rapid proceeding to clinical testing. However, freewheeling evolutionary developments of the stem cell theory might lead to dystopian scenarios where heterogeneous sources of therapeutic cells could promote mixed clinical outcomes in un-stratified patient populations. This review focuses on the lessons that should be learnt from the first generation of stem cell-based strategies and emphasizes the absolute requirement to better understand the basic mechanisms of stem cell biology and cardiogenesis. We will also discuss about the unexpected “big bang” in the stem cell theory, “blasting” the therapeutic cells to their unchallenged ability to release paracrine factors such as extracellular membrane vesicles. Paradoxically, the natural evolution of the stem cell theory for cardiac regeneration may end with the development of cell-free strategies with multiple cellular targets including cardiomyocytes but also other infiltrating or resident cardiac cells.

  18. Improve T Cell Therapy in Neuroblastoma

    Science.gov (United States)

    2015-09-01

    down regulation in LTE-T cells is not caused by specific culture conditions. T lymphocytes were activated with immobilized OKT3 (1 μg ml) and...a lethal acute respiratory distress syndrome and severe eosinophilia were reported in a patient vaccinated with irradiated autologous myeloblasts...condition ‘day 15’ indicates HPSE expression in LTE-T cells cultured for 14 d and re-stimulated with immobilized OKT3 and CD28-specific antibodies

  19. Nanoelectroablation therapy for murine basal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nuccitelli, Richard, E-mail: rich@bioelectromed.com [BioElectroMed Corp., 849 Mitten Rd., Suite 104, Burlingame, CA 94010 (United States); Tran, Kevin; Athos, Brian; Kreis, Mark; Nuccitelli, Pamela [BioElectroMed Corp., 849 Mitten Rd., Suite 104, Burlingame, CA 94010 (United States); Chang, Kris S.; Epstein, Ervin H. [The Children' s Hospital Oakland Research Institute, Oakland, CA 94609 (United States); Tang, Jean Y. [The Children' s Hospital Oakland Research Institute, Oakland, CA 94609 (United States); Stanford University, Stanford, CA 94305 (United States)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Nanoelectroablation is a new, non-thermal therapy that triggers apoptosis in tumors. Black-Right-Pointing-Pointer Low energy, ultrashort, high voltage pulses ablate the tumor with little or no scar. Black-Right-Pointing-Pointer Nanoelectroablation eliminates 99.8% of the BCC but may leave a few remnants behind. Black-Right-Pointing-Pointer Pilot clinical trials on human BCCs are ongoing and leave no remnants in most cases. -- Abstract: When skin tumors are exposed to non-thermal, low energy, nanosecond pulsed electric fields (nsPEF), apoptosis is initiated both in vitro and in vivo. This nanoelectroablation therapy has already been proven effective in treating subdermal murine allograft tumors. We wanted to determine if this therapy would be equally effective in the treatment of autochthonous BCC tumors in Ptch1{sup +/-}K14-Cre-ER p53 fl/fl mice. These tumors are similar to human BCCs in histology and in response to drug therapy . We have treated 27 BCCs across 8 mice with either 300 pulses of 300 ns duration or 2700 pulses of 100 ns duration, all at 30 kV/cm and 5-7 pulses per second. Every nsPEF-treated BCC began to shrink within a day after treatment and their initial mean volume of 36 {+-} 5 (SEM) mm{sup 3} shrunk by 76 {+-} 3% over the ensuing two weeks. After four weeks, they were 99.8% ablated if the size of the treatment electrode matched the tumor size. If the tumor was larger than the 4 mm wide electrode, multiple treatments were needed for complete ablation. Treated tumors were harvested for histological analysis at various times after treatment and exhibited apoptosis markers. Specifically, pyknosis of nuclei was evident as soon as 2 days after nsPEF treatment, and DNA fragmentation as detected via TUNEL staining was also evident post treatment. Nanoelectroablation is effective in triggering apoptosis and remission of radiation-induced BCCs with a single 6 min-long treatment of 2700 pulses.

  20. Imaging: Guiding the Clinical Translation of Cardiac Stem Cell Therapy

    Science.gov (United States)

    Nguyen, Patricia K.; Lan, Feng; Wang, Yongming; Wu, Joseph C.

    2011-01-01

    Stem cells have been touted as the holy grail of medical therapy with promises to regenerate cardiac tissue, but it appears the jury is still out on this novel therapy. Using advanced imaging technology, scientists have discovered that these cells do not survive nor engraft long-term. In addition, only marginal benefit has been observed in large animal studies and human trials. However, all is not lost. Further application of advanced imaging technology will help scientists unravel the mysteries of stem cell therapy and address the clinical hurdles facing its routine implementation. In this review, we will discuss how advanced imaging technology will help investigators better define the optimal delivery method, improve survival and engraftment, and evaluate efficacy and safety. Insights gained from this review may direct the development of future preclinical investigations and clinical trials. PMID:21960727

  1. Mesenchymal stem cell therapies in the treatment of musculoskeletal diseases.

    Science.gov (United States)

    Bashir, Jamil; Sherman, Andrew; Lee, Henry; Kaplan, Lee; Hare, Joshua M

    2014-01-01

    The application of regenerative strategies to musculoskeletal ailments offers extraordinary promise to transform management of the conditions of numerous patients. The use of cell-based therapies and adjunct strategies is under active investigation for injuries and illnesses affecting bones, joints, tendons, and skeletal muscle. Of particular interest to the field is the mesenchymal stem cell, an adult stem cell found in bone marrow and adipose tissue. This cell type can be expanded ex vivo, has allogeneic application, and has the capacity for engraftment and differentiation into mesodermal lineages. Also of major interest in the field is the use of platelet-rich plasma, a strategy to concentrate endogenous cytokines and growth factors with reparative potential. Here we review the biological basis, clinical studies, safety, and current state of mesenchymal stem cell and platelet-rich plasma therapies in the treatment of musculoskeletal disease. Copyright © 2014 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  2. Anti-B cell antibody therapies for inflammatory rheumatic diseases

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Jayne, David R W

    2014-01-01

    Several monoclonal antibodies targeting B cells have been tested as therapeutics for inflammatory rheumatic diseases. We review important observations from randomized clinical trials regarding the efficacy and safety of anti-B cell antibody-based therapies for rheumatoid arthritis, systemic lupus...... erythematosus, antineutrophil cytoplasmic antibody-associated vasculitis, polymyositis/dermatomyositis, and primary Sjögren's syndrome. For some anti-B cell agents, clinical benefits have been convincingly demonstrated, while other B cell-targeted therapies failed to improve outcomes when added to standard...... and functions in rheumatic disorders. Future studies should also evaluate how to maintain disease control by means of conventional and/or biologic immunosuppressants after remission-induction with anti-B cell antibodies....

  3. PET molecular imaging in stem cell therapy for neurological diseases

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiachuan; Zhang, Hong [Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Nuclear Medicine, Hangzhou, Zhejiang (China); Zhejiang University, Medical PET Center, Hangzhou (China); Institute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou (China); Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou (China); Tian, Mei [University of Texas, M.D. Anderson Cancer Center, Department of Experimental Diagnostic Imaging, Houston, TX (United States)

    2011-10-15

    Human neurological diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal cord injury and multiple sclerosis are caused by loss of different types of neurons and glial cells in the brain and spinal cord. At present, there are no effective therapies against these disorders. Discovery of the therapeutic potential of stem cells offers new strategies for the treatment of neurological diseases. Direct assessment of stem cells' survival, interaction with the host and impact on neuronal functions after transplantation requires advanced in vivo imaging techniques. Positron emission tomography (PET) is a potential molecular imaging modality to evaluate the viability and function of transplanted tissue or stem cells in the nervous system. This review focuses on PET molecular imaging in stem cell therapy for neurological diseases. (orig.)

  4. CHRONIC HEART FAILURE OF ISCHEMIC GENESIS AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE: POSSIBILITIES OF COMBINATION THERAPY INCLUDING NEBIVOLOL

    Directory of Open Access Journals (Sweden)

    P. A. Fedotov

    2013-01-01

    Full Text Available Objective: to reveal the features of chronic heart failure (CHF of ischemic genesis concurrent with chronic obstructive pulmonary disease (COPD and to investigate the effect of the cardioselective β1-adrenoblocker (β1-AB nebivolol on the course of COPD and the parameters of the bronchopulmonary system in patients with CHF of ischemic genesis during treatment.Subjects and methods.The investigation enrolled 63 patients aged 40–70 years, including 43 patients with functional class (FC II–IV CHF with a Simpson left ventricular ejection fraction of  45 % concurrent with COPD (a study group and 20 patients with CHF and no bronchopulmonary pathology (a control group. The study group patients were randomly divided into 2 subgroups: 1 23 patients who received nebivolol in addition to background therapy; 2 20 patients in whom the therapy ruled out the use of β1-AB. The control patients were switched to nebivolol therapy. During 6-month follow-up, the authors made clinical examination, recorded the rate, duration, and severity of COPD exacerbations, performed a 6-minute walking test (6MWT, and used a clinical status scale modified by R. Cody, a dyspnea 0–10 category ratio (Borg scale, and a Medical Research Council Dyspnoea Scale (MRS scale. Besides, quality of life in patients was assessed using the specific Minnesota Living with Heart Failure Questionnaire. All the patients underwent echocardiography, bronchodilatation-induced external respiratory function test, peak flowmetry, and blood brain natriuretic peptide quantification. These studies were conducted at baseline and at 1 and 6 months of therapy.Results. During the investigation, the patients with CHF concurrent with COPD were found to have a high rate of hypertensive disease, prior myocardial infarctions, atrial fibrillations, and higher FC exertional angina. These patients also showed a delayed optimal result achievement during the combination therapy involving the use of β1-AB

  5. CHRONIC HEART FAILURE OF ISCHEMIC GENESIS AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE: POSSIBILITIES OF COMBINATION THERAPY INCLUDING NEBIVOLOL

    Directory of Open Access Journals (Sweden)

    P. A. Fedotov

    2014-07-01

    Full Text Available Objective: to reveal the features of chronic heart failure (CHF of ischemic genesis concurrent with chronic obstructive pulmonary disease (COPD and to investigate the effect of the cardioselective β1-adrenoblocker (β1-AB nebivolol on the course of COPD and the parameters of the bronchopulmonary system in patients with CHF of ischemic genesis during treatment.Subjects and methods.The investigation enrolled 63 patients aged 40–70 years, including 43 patients with functional class (FC II–IV CHF with a Simpson left ventricular ejection fraction of  45 % concurrent with COPD (a study group and 20 patients with CHF and no bronchopulmonary pathology (a control group. The study group patients were randomly divided into 2 subgroups: 1 23 patients who received nebivolol in addition to background therapy; 2 20 patients in whom the therapy ruled out the use of β1-AB. The control patients were switched to nebivolol therapy. During 6-month follow-up, the authors made clinical examination, recorded the rate, duration, and severity of COPD exacerbations, performed a 6-minute walking test (6MWT, and used a clinical status scale modified by R. Cody, a dyspnea 0–10 category ratio (Borg scale, and a Medical Research Council Dyspnoea Scale (MRS scale. Besides, quality of life in patients was assessed using the specific Minnesota Living with Heart Failure Questionnaire. All the patients underwent echocardiography, bronchodilatation-induced external respiratory function test, peak flowmetry, and blood brain natriuretic peptide quantification. These studies were conducted at baseline and at 1 and 6 months of therapy.Results. During the investigation, the patients with CHF concurrent with COPD were found to have a high rate of hypertensive disease, prior myocardial infarctions, atrial fibrillations, and higher FC exertional angina. These patients also showed a delayed optimal result achievement during the combination therapy involving the use of β1-AB

  6. A systematic review of in-hospital worsening heart failure as an endpoint in clinical investigations of therapy for acute heart failure.

    Science.gov (United States)

    Fonseca, Cândida; Maggioni, Aldo Pietro; Marques, Filipa; Araújo, Inês; Brás, Daniel; Langdon, Ronald B; Lombardi, Carlo; Bettencourt, Paulo

    2018-01-01

    In-hospital worsening heart failure (WHF) occurs frequently in patients hospitalized for acute heart failure (AHF) and has strongly negative prognostic associations. It may be a useful endpoint in studies of AHF management but important questions remain regarding optimization of its definition and variability in its incidence. Our objective was to survey the full extent of clinical interest in WHF and assess the impact of baseline variables and trial design on outcomes. PubMed, Embase, and BIOSIS were searched systematically for clinical studies that had in-hospital WHF as an endpoint. Differences in definitions of in-hospital WHF were reviewed for their potential impact on observed incidence of WHF and its associations with post-discharge outcomes. The search identified 35 publications representing 13 interventional trials, 3 observational studies, several different classes of therapeutic agent, and 78,752 patients overall. Incidence of in-hospital WHF varied greatly-from 4.2% to 37%. Concerning the impact of differences in the way in which WHF was defined, two important factors were physician determination of worsening and whether intensification of diuretic therapy alone was defined as a WHF event. Patients having in-hospital WHF were at substantially greater risk for death and longer length of stay during index hospitalizations, all-cause and heart-failure rehospitalization, cardiovascular complications, renal failure, all-cause death, cardiovascular death, and higher healthcare costs post-discharge. There is diverse interest in selecting in-hospital WHF as an endpoint in clinical trials. Differences in reported incidence are complexly related to differences in the way in which WHF is defined. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  7. Stem Cell Therapy for Erectile Dysfunction: Progress and Future Directions.

    Science.gov (United States)

    Albersen, Maarten; Weyne, Emmanuel; Bivalacqua, Trinity J

    2013-05-01

    Erectile dysfunction (ED) is the most common sexual disorder reported by men to their health-care providers and the most investigated male sexual dysfunction. Currently, the treatment of ED focuses on symptomatic relief of ED and therefore tends to provide temporary relief rather than providing a cure or reversing the underlying cause. Recently, stem cell-based therapies have received increasing attention regarding their potential for the recovery of erectile function. Preclinical studies have shown that these cells may reverse pathophysiological changes leading to ED rather than treating the symptom ED. To review available evidence on the efficacy and mechanisms of action of stem cell application for the treatment of ED. A nonsystematic review was conducted on the available English literature between 1966 and 2013 on the search engines SciVerse-sciencedirect, SciVerse-scopus, Google Scholar, and PubMed. Several preclinical studies have addressed stem cell-based therapies for the recovery of erectile function following cavernous nerve injury and in Peyronie's disease, diabetes, aging, and hyperlipidemia. Overall, these studies have shown beneficial effects of stem cell therapy, while evidence on the mechanisms of action of stem cell therapy still varies between studies. While many authors propose engraftment and differentiation of stem cells, a recent paradigm shift toward paracrine mechanisms of action is observed. One clinical study investigated stem cell therapy in diabetic patients, and two more clinical trials are currently recruiting patients. The development of methods to deliver stem cells to the penis has kindled a keen interest in understanding stem cell biology as it related to restoration of normal penile vascular and neuronal homeostasis. The use of stem cells for the treatment of ED represents an exciting new field, which still requires extensive basic research and human trials in diverse ED patient populations in order to define its role in the

  8. Influence of induction therapy, immunosuppressive regimen and anti-viral prophylaxis on development of lymphomas after heart transplantation: data from the Spanish Post-Heart Transplant Tumour Registry.

    Science.gov (United States)

    Crespo-Leiro, Maria G; Alonso-Pulpón, Luis; Arizón, José M; Almenar, Luis; Delgado, Juan F; Palomo, Jesús; Manito, Nicolás; Rábago, Gregorio; Lage, Ernesto; Diaz, Beatriz; Roig, Eulalia; Pascual, Domingo; Blasco, Teresa; de la Fuente, Luis; Campreciós, Marta; Vázquez de Prada, José A; Muñiz, Javier

    2007-11-01

    Lymphoma after heart transplantation (HT) has been associated with induction therapy and herpesvirus infection. It is not known whether anti-viral agents administered immediately after HT can reduce the incidence of lymphoma. This study was a retrospective review of 3,393 patients who underwent HT in Spain between 1984 and December 2003. Variables examined included development of lymphoma and, as possible risk factors, recipient gender and age, induction therapies (anti-thymocyte globulin, OKT3 and anti-interleukin-2 receptor antibodies) and anti-viral prophylaxis (acyclovir or ganciclovir). To study the effect of evolving treatment strategy, three HT eras were considered: 1984 to 1995; 1996 to 2000; and 2001 to 2003. Induction therapy was employed in >60% of HTs, and anti-viral prophylaxis in >50%. There were 62 cases of lymphoma (3.1 per 1,000 person-years, 95% confidence interval: 2.4 to 4.0). Univariate analyses showed no influence of gender, age at transplant, HT era, pre-HT smoking or the immunosuppressive maintenance drugs used in the first 3 months post-HT. The induction agent anti-thymocyte globulin (ATG) was associated with increased risk of lymphoma, and prophylaxis with acyclovir with decreased risk of lymphoma. Multivariate analyses (controlling for age group, gender, pre-HT smoking and immunosuppression in the first 3 months with mycophenolate mofetil and/or tacrolimus) showed that induction increased the risk of lymphoma if anti-viral prophylaxis was not used (regardless of induction agent and anti-viral agent), but did not increase the risk if anti-viral prophylaxis was used. Induction therapies with ATG or OKT3 do or do not increase the risk of lymphoma depending on whether anti-viral prophylaxis with acyclovir or ganciclovir is or is not employed, respectively.

  9. Stem Cell Therapy to Improve Burn Wound Healing

    Science.gov (United States)

    2017-03-01

    Award Number: W81XWH-13-2-0024 TITLE: Stem Cell Therapy to Improve Burn Wound Healing PRINCIPAL INVESTIGATOR: Carl Schulman, MD, PhD, MSPH...NUMBER Stem Cell Therapy to Improve Burn Wound Healing 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Carl Schulman, MD, PhD, MSPH...ES) 8. PERFORMING ORGANIZATION REPORT NUMBER Univ ersity of Miam i M Miller School of Medicine Ryder Trauma Center 1800 NW 10th Avenue, Suite 221

  10. Stem Cell Therapy for Treatment of Ocular Disorders.

    Science.gov (United States)

    Sivan, Padma Priya; Syed, Sakinah; Mok, Pooi-Ling; Higuchi, Akon; Murugan, Kadarkarai; Alarfaj, Abdullah A; Munusamy, Murugan A; Awang Hamat, Rukman; Umezawa, Akihiro; Kumar, Suresh

    2016-01-01

    Sustenance of visual function is the ultimate focus of ophthalmologists. Failure of complete recovery of visual function and complications that follow conventional treatments have shifted search to a new form of therapy using stem cells. Stem cell progenitors play a major role in replenishing degenerated cells despite being present in low quantity and quiescence in our body. Unlike other tissues and cells, regeneration of new optic cells responsible for visual function is rarely observed. Understanding the transcription factors and genes responsible for optic cells development will assist scientists in formulating a strategy to activate and direct stem cells renewal and differentiation. We review the processes of human eye development and address the strategies that have been exploited in an effort to regain visual function in the preclinical and clinical state. The update of clinical findings of patients receiving stem cell treatment is also presented.

  11. Stem Cell Therapy for Treatment of Ocular Disorders

    Directory of Open Access Journals (Sweden)

    Padma Priya Sivan

    2016-01-01

    Full Text Available Sustenance of visual function is the ultimate focus of ophthalmologists. Failure of complete recovery of visual function and complications that follow conventional treatments have shifted search to a new form of therapy using stem cells. Stem cell progenitors play a major role in replenishing degenerated cells despite being present in low quantity and quiescence in our body. Unlike other tissues and cells, regeneration of new optic cells responsible for visual function is rarely observed. Understanding the transcription factors and genes responsible for optic cells development will assist scientists in formulating a strategy to activate and direct stem cells renewal and differentiation. We review the processes of human eye development and address the strategies that have been exploited in an effort to regain visual function in the preclinical and clinical state. The update of clinical findings of patients receiving stem cell treatment is also presented.

  12. Enhancing human regulatory T cells in vitro for cell therapy applications.

    Science.gov (United States)

    Milward, Kate F; Wood, Kathryn J; Hester, Joanna

    2017-10-01

    Adoptive cellular therapies are gaining popularity as a means to treat clinical conditions, with potentially fewer risks and greater efficacy than traditional pharmacological strategies. Regulatory T cells (Tregs) are currently undergoing clinical trials in various immune-mediated pathologies, including transplant rejection and autoimmune conditions. In general, cell therapy relies upon ex vivo expansion of the cell product, in order to administer more cells than can be isolated from one person. In vitro manipulation of cell therapy products, prior to administration to patients, offers the opportunity to enhance the efficacy of the final cell therapy product in other ways. For example, cells can be exposed to reagents that enhance their longevity or functional potency after transfer into the patient. Genetic modification strategies can even permit the design of cells with bespoke functionality. Crucially, in vitro manipulation of therapeutic cells in isolation can exert these influences upon the biology of the therapeutic cells, without systemic exposure of the patient to the reagents being used. Quality control assessments can be integrated into the procedure prior to administration, to protect the patient from the risk of adverse events, should the procedure produce undesirable results. With a particular focus on Tregs, this review surveys the diverse strategies that are being employed to enhance the efficacy of cell therapy via in vitro manipulation of cells, and highlights some emerging technologies that may propel this endeavour in the future. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  13. Total heart volume as a function of clinical and anthropometric parameters in a population of external beam radiation therapy patients

    Science.gov (United States)

    Nadège Ilembe Badouna, Audrey; Veres, Cristina; Haddy, Nadia; Bidault, François; Lefkopoulos, Dimitri; Chavaudra, Jean; Bridier, André; de Vathaire, Florent; Diallo, Ibrahima

    2012-01-01

    The aim of this paper was to determine anthropometric parameters leading to the least uncertain estimate of heart size when connecting a computational phantom to an external beam radiation therapy (EBRT) patient. From computed tomography images, we segmented the heart and calculated its total volume (THV) in a population of 270 EBRT patients of both sexes, aged 0.7-83 years. Our data were fitted using logistic growth functions. The patient age, height, weight, body mass index and body surface area (BSA) were used as explanatory variables. For both genders, good fits were obtained with both weight (R2 = 0.89 for males and 0.83 for females) and BSA (R2 = 0.90 for males and 0.84 for females). These results demonstrate that, among anthropometric parameters, weight plays an important role in predicting THV. These findings should be taken into account when assigning a computational phantom to a patient.

  14. Cardiac resynchronization therapy in patients with heart failure and atrial fibrillation : importance of new-onset atrial fibrillation and total atrial conduction time

    NARCIS (Netherlands)

    Buck, Sandra; Rienstra, Michiel; Maass, Alexander H.; Nieuwland, Wybe; Van Veldhuisen, Dirk J.; Van Gelder, Isabelle C.

    AIMS: Cardiac resynchronization therapy (CRT) is an established therapy for patients with heart failure and sinus rhythm (SR), but its value in atrial fibrillation (AF) remains unclear. Furthermore, response to CRT may be difficult to predict in these patients. The aim of our study was to

  15. The effects of short-term relaxation therapy on indices of heart rate variability and blood pressure in young adults.

    Science.gov (United States)

    Pal, Gopal Krushna; Ganesh, Venkata; Karthik, Shanmugavel; Nanda, Nivedita; Pal, Pravati

    2014-01-01

    Assessment of short-term practice of relaxation therapy on autonomic and cardiovascular functions in first-year medical students. Case-control, interventional study. Medical college laboratory. Sixty-seven medical students, divided into two groups: study group (n = 35) and control group (n = 32). Study group subjects practiced relaxation therapy (shavasana with a soothing background music) daily 1 hour for