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Cardiac stem cell

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https://www.readbyqxmd.com/read/29226427/case-report-treatment-of-light-chain-amyloidosis-with-daratumumab-monotherapy-in-two-patients
#1
Charlotte Gran, Gösta Gahrton, Evren Alici, Hareth Nahi
Immunoglobulin light-chain amyloidosis (AL) affects multiple organs, most prominently the kidney and the heart. Renal and cardiac impairment are both associated with poor prognosis.(1) Typical treatment regimens for AL include proteasome inhibitors, alkylating agents, and steroids as well as autologous stem cell transplantation (ASCT) for younger, fit patients. Complete response after treatment is associated with a better outcome and can be measured by free light chain (FLC) reduction.(2, 3) Monoclonal antibodies such as daratumumab (Dara, human IgG1 anti-CD38) have shown promising efficacy for the treatment of relapsed and refractory multiple myeloma...
December 11, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29225198/perspective-in-optimization-of-stem-cell-therapies-for-heart-regeneration
#2
Paulina Gapska, Maciej Kurpisz
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...
December 7, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/29223373/adverse-prognostic-factors-for-morbidity-and-mortality-during-peripheral-blood-stem-cell-mobilization-in-patients-with-light-chain-amyloidosis
#3
Jason C Yeh, Brandon R Shank, Denái R Milton, Muzaffar H Qazilbash
Patients with immunoglobulin light chain (AL) amyloidosis undergoing peripheral blood hematopoietic stem cell (PBSC) mobilization for autologous hematopoietic stem cell transplantation (auto-HCT) can experience significant morbidity and mortality. The purpose of this study was to describe the adverse events and identify prognostic factors associated with the development of morbidity and mortality in patients with AL amyloidosis who had begun PBSC mobilization for auto-HCT. A retrospective study was performed in 101 consecutive patients with AL amyloidosis who underwent PBSC mobilization for auto-HCT between January 2006 and December 2013...
December 6, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29218360/bioengineered-cardiac-tissue-based-on-human-stem-cells-for-clinical-application
#4
Monica Jara Avaca, Ina Gruh
Engineered cardiac tissue might enable novel therapeutic strategies for the human heart in a number of acquired and congenital diseases. With recent advances in stem cell technologies, namely the availability of pluripotent stem cells, the generation of potentially autologous tissue grafts has become a realistic option. Nevertheless, a number of limitations still have to be addressed before clinical application of engineered cardiac tissue based on human stem cells can be realized. We summarize current progress and pending challenges regarding the optimal cell source, cardiomyogenic lineage specification, purification, safety of genetic cell engineering, and genomic stability...
December 8, 2017: Advances in Biochemical Engineering/biotechnology
https://www.readbyqxmd.com/read/29217753/wnt-inhibition-promotes-vascular-specification-of-embryonic-cardiac-progenitors
#5
David Reichman, Laura Park, Limor Man, David Redmond, Kenny Chao, Richard P Harvey, Makoto M Taketo, Zev Rosenwaks, Daylon James
Several studies have demonstrated a multiphasic role for Wnt signaling during embryonic cardiogenesis (Naito et al., 2006; Qyang et al., 2007) and developed protocols that enrich for cardiac derivatives during in vitro differentiation of human pluripotent stem cells (hPSC) (Elliott et al., 2011; Iyer et al., 2016; Lian et al., 2012; Paige et al., 2010; Willems et al., 2011; Witty et al., 2014), however, few studies have investigated the role of Wnt signaling in specification of cardiac progenitor cells (CPC) toward downstream fates...
December 7, 2017: Development
https://www.readbyqxmd.com/read/29217433/hypertrophic-cardiomyopathy-linked-mutation-in-troponin-t-causes-myofibrillar-disarray-and-pro-arrhythmic-action-potential-changes-in-human-ipsc-cardiomyocytes
#6
Lili Wang, Kyungsoo Kim, Shan Parikh, Adrian Gabriel Cadar, Kevin R Bersell, Huan He, Jose R Pinto, Dmytro O Kryshtal, Bjorn C Knollmann
BACKGROUND: Mutations in cardiac troponin T (TnT) are linked to increased risk of ventricular arrhythmia and sudden death despite causing little to no cardiac hypertrophy. Studies in mice suggest that the hypertrophic cardiomyopathy (HCM)-associated TnT-I79N mutation increases myofilament Ca sensitivity and is arrhythmogenic, but whether findings from mice translate to human cardiomyocyte electrophysiology is not known. OBJECTIVES: To study the effects of the TnT-I79N mutation in human cardiomyocytes...
December 4, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29217199/efficient-generation-of-transgene-and-feeder-free-induced-pluripotent-stem-cells-from-human-dental-mesenchymal-stem-cells-and-their-chemically-defined-differentiation-into-cardiomyocytes
#7
Xiaobing Tan, Qingli Dai, Tao Guo, Jingshu Xu, Qingyuan Dai
Advance in stem cell research resulted in several processes to generate induced pluripotent stem cells (iPSCs) from adult somatic cells. In our previous study, the reprogramming of iPSCs from human dental mesenchymal stem cells (MSCs) including SCAP and DPSCs, has been reported. Herein, safe iPSCs were reprogrammed from SCAP and DPSCs using non-integrating RNA virus vector, which is an RNA virus carrying no risk of altering host genome. DPSCs- and SCAP-derived iPSCs exhibited the characteristics of the classical morphology with human embryonic stem cells (hESCs) without integration of foreign genes, indicating the potential of their clinical application...
December 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29216651/regenerative-medicine-cardiac-cell-therapy-pluripotent-stem-cells
#8
Ana G Duran, Olivia Reidell, Harald Stachelscheid, Kristin Klose, Manfred Gossen, Volkmar Falk, Wilhelm Röll, Christof Stamm
No abstract text is available yet for this article.
December 7, 2017: Thoracic and Cardiovascular Surgeon
https://www.readbyqxmd.com/read/29216265/oct4-expression-mediates-partial-cardiomyocyte-reprogramming-of-mesenchymal-stromal-cells
#9
Gustavo Yannarelli, Natalia Pacienza, Sonia Montanari, Diego Santa-Cruz, Sowmya Viswanathan, Armand Keating
Mesenchymal stem/stromal cells (MSCs) are in numerous cell therapy clinical trials, including for injured myocardium. Acquisition of cardiomyocyte characteristics by MSCs may improve cardiac regeneration but the mechanisms regulating this process are unclear. Here, we investigated whether the pluripotency transcription factor OCT4 is involved in the activation of cardiac lineage genetic programs in MSCs. We employed our established co-culture model of MSCs with rat embryonic cardiomyocytes showing co-expression of cardiac markers on MSCs independent of cell fusion...
2017: PloS One
https://www.readbyqxmd.com/read/29212969/-analysis-of-long-term-survivors-with-cardiac-al-amyloidosis
#10
Kumiko Kagawa, Yusaku Maeda, Masahiro Oura, Kimiko Sogabe, Hikaru Fujino, Mamiko Takahashi, Tomoko Maruhashi, Masami Iwasa, Kengo Udaka, Takeshi Harada, Takayuki Ise, Shiro Fujii, Shingen Nakamura, Hirokazu Miki, Shusuke Yagi, Kyoko Takeuchi, Shuji Ozaki, Masahiro Abe
Cardiac AL amyloidosis (CA) is generally known as a severe disease with very poor prognosis. Here we retrospectively examined seven patients with CA in our cohort who achieved long-term survival. All six patients who underwent high-dose melphalan and autologous stem cell transplantation (ASCT) survived for >3 years, whereas four patients survived for >5 years. Patients who underwent ASCT had prompt hematological responses, and five patients showed organ responses. ASCT helps to achieve a quick and deep hematological response required for long-term survival in patients with CA...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29212899/novel-mutation-in-flnc-filamin-c-causes-familial-restrictive-cardiomyopathy
#11
Nathan R Tucker, Micheal A McLellan, Dongjian Hu, Jiangchuan Ye, Victoria A Parsons, Robert W Mills, Sebastian Clauss, Elena Dolmatova, Marisa A Shea, David J Milan, Nandita S Scott, Mark Lindsay, Steven A Lubitz, Ibrahim J Domian, James R Stone, Honghuang Lin, Patrick T Ellinor
BACKGROUND: Restrictive cardiomyopathy (RCM) is a rare cardiomyopathy characterized by impaired diastolic ventricular function resulting in a poor clinical prognosis. Rarely, heritable forms of RCM have been reported, and mutations underlying RCM have been identified in genes that govern the contractile function of the cardiomyocytes. METHODS AND RESULTS: We evaluated 8 family members across 4 generations by history, physical examination, electrocardiography, and echocardiography...
December 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/29212896/the-novel-desmin-mutation-p-glu401asp-impairs-filament-formation-disrupts-cell-membrane-integrity-and-causes-severe-arrhythmogenic-left-ventricular-cardiomyopathy-dysplasia
#12
Francisco José Bermúdez-Jiménez, Víctor Carriel, Andreas Brodehl, Miguel Alaminos, Antonio Campos, Ilona Schirmer, Hendrik Milting, Beatriz Álvarez Abril, Miguel Álvarez, Silvia López-Fernández, Diego García-Giustiniani, Lorenzo Monserrat, Luis Tercedor, Juan Jiménez-Jáimez
Background -Desmin (DES) mutations cause severe skeletal and cardiac muscle disease with heterogeneous phenotypes. Recently, DES mutations were described in patients with inherited arrhythmogenic right ventricular cardiomyopathy/dysplasia (iARVC/D), although their cellular and molecular pathomechanisms are not precisely known. Our aim is to describe clinically and functionally the novel DES-p.Glu401Asp mutation as a cause of inherited left ventricular arrhythmogenic cardiomyopathy/dysplasia (iLVAC/D). Methods -We identified the novel DES mutation p...
December 6, 2017: Circulation
https://www.readbyqxmd.com/read/29211342/functional-bkca-channel-in-human-resident-cardiac-stem-cells-expressing-w8b2
#13
Oualid Ayad, Christophe Magaud, Stéphane Sebille, Jocelyn Bescond, Chloé Mimbimi, Christian Cognard, Jean-Francois Faivre, Patrick Bois, Aurelien Chatelier
Recently, a new population of resident cardiac stem cells positive for W8B2 marker has been identified. These cardiac stem cells (CSCs) are considered as an ideal cellular source to repair myocardial damage after infarction. However, the electrophysiological profile of these cells has not been characterized yet. We first establish the conditions of isolation and expansion of W8B2+ CSCs from human heart biopsies using magnetic sorting system followed by flow cytometry cell sorting. These cells display a spindle-shaped morphology, are highly proliferative and possess self-renewal capacity demonstrated by their ability to form colonies...
December 6, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29211031/frequency-dependent-multi-well-cardiotoxicity-screening-enabled-by-optogenetic-stimulation
#14
Susanne Rehnelt, Daniela Malan, Krisztina Juhasz, Benjamin Wolters, Leo Doerr, Matthias Beckler, Ralf Kettenhofen, Heribert Bohlen, Tobias Bruegmann, Philipp Sasse
Side effects on cardiac ion channels causing lethal arrhythmias are one major reason for drug withdrawals from the market. Field potential (FP) recording from cardiomyocytes, is a well-suited tool to assess such cardiotoxic effects of drug candidates in preclinical drug development, but it is currently limited to the spontaneous beating of the cardiomyocytes and manual analysis. Herein, we present a novel optogenetic cardiotoxicity screening system suited for the parallel automated frequency-dependent analysis of drug effects on FP recorded from human-induced pluripotent stem cell-derived cardiomyocytes...
December 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29209617/mirroring-the-multiple-potentials-of-micrornas-in-acute-myocardial-infarction
#15
REVIEW
Solenne Paiva, Onnik Agbulut
At present, cardiovascular diseases are depicted to be the leading cause of death worldwide according to the World Health Organization. In the future, projections predict that ischemic heart disease will persist in the top main causes of illness. Within this alarming context, some tiny master regulators of gene expression programs, namely, microRNAs (miRNAs) carry three promising potentials. In fact, miRNAs can prove to be useful not only in terms of biomarkers allowing heart injury detection but also in terms of therapeutics to overcome limitations of past strategies and treat the lesions...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29209319/mesenchymal-stem-cells-induce-expression-of-cd73-in-human-monocytes-in-vitro-and-in-a-swine-model-of-myocardial-infarction-in-vivo
#16
Marta Monguió-Tortajada, Santiago Roura, Carolina Gálvez-Montón, Marcella Franquesa, Antoni Bayes-Genis, Francesc E Borràs
The ectoenzymes CD39 and CD73 regulate the purinergic signaling through the hydrolysis of adenosine triphosphate (ATP)/ADP to AMP and to adenosine (Ado), respectively. This shifts the pro-inflammatory milieu induced by extracellular ATP to the anti-inflammatory regulation by Ado. Mesenchymal stem cells (MSCs) have potent immunomodulatory capabilities, including monocyte modulation toward an anti-inflammatory phenotype aiding tissue repair. In vitro, we observed that human cardiac adipose tissue-derived MSCs (cATMSCs) and umbilical cord MSCs similarly polarize monocytes toward a regulatory M2 phenotype, which maintained the expression of CD39 and induced expression of CD73 in a cell contact dependent fashion, correlating with increased functional activity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29208679/the-time-trial-effect-of-timing-of-stem-cell-delivery-following-st-elevation-myocardial-infarction-on-the-recovery-of-global-and-regional-left-ventricular-function-final-2-year-analysis
#17
Jay H Traverse, Timothy D Henry, Carl J Pepine, James T Willerson, Atul R Chugh, Phillip C Yang, David Zhao, Stephen G Ellis, John R Forder, Emerson C Perin, Marc S Penn, Antonis K Hatzopoulos, Jeffrey W Chambers, Kenneth Baran, Ganesh Raveendran, Adrian P Gee, Doris A Taylor, Lem Moyé, Ray F Ebert, Robert D Simari
Rationale: The TIME trial was the first cell therapy trial sufficiently powered to determine if timing of cell delivery following ST-elevation myocardial infarction (STEMI) affects recovery of left ventricular (LV) function. Objective: To report the 2-year clinical and cardiac magnetic resonance imaging (cMRI) results and their modification by microvascular obstruction (MVO). Methods and Results: TIME was a randomized, double-blind, placebo-controlled trial comparing 150 million bone marrow mononuclear cells (BMC) vs...
December 5, 2017: Circulation Research
https://www.readbyqxmd.com/read/29207187/macrophage-migration-inhibitory-factor-rescues-mesenchymal-stem-cells-from-doxorubicin-induced-senescence-though-the-pi3k-akt-signaling-pathway
#18
Wenzheng Xia, Meng Hou
Doxorubicin (DOXO), an anthracycline antibiotic, is a commonly used anticancer drug. Despite its widespread usage, the therapeutic effects of DOXO are limited by its cardiotoxicity. Mesenchymal stem cell (MSC)-based therapies have had positive outcomes in the treatment of DOXO-induced cardiac damage; however, DOXO exerts toxic effects on MSCs, decreasing the effectiveness of MSC therapy. Macrophage migration inhibitory factor (MIF) promotes MSC survival and rejuvenation, and thus is a promising candidate to protect MSCs against DOXO-induced injury...
November 23, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29207135/bfgf-promotes-sca%C3%A2-1-cardiac-stem-cell-migration-through-activation-of-the-pi3k-akt-pathway
#19
Lin Ling, Shaohua Gu, Yan Cheng, Liucheng Ding
Cardiac stem cells (CSCs) are important for improving cardiac function following myocardial infarction, with CSC migration to infarcted or ischemic myocardium important for cardiac regeneration. Strategies to improve cell migration may improve the efficiency of myocardial regeneration. Basic fibroblast growth factor (bFGF) is an essential molecule in cell migration, but the endogenous bFGF level is too low to be effective. The effect of exogenously delivered bFGF on CSC migration was observed in vitro and in vivo in the present study...
November 28, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29207072/transcription-factor-tbx18-promotes-adult-rat-bone-mesenchymal-stem-cell-differentiation-to-biological-pacemaker-cells
#20
Yanjun Li, Mei Yang, Gege Zhang, Le Li, Bingjie Ye, Congxin Huang, Yanhong Tang
Bone mesenchymal stem cells (BMSCs) are currently considered the optimal stem cells for biological pacemaker cell transformation. The cardiac‑specific transcription factor T‑Box protein 18 (TBX18) is essential for sinoatrial node (SAN) formation, particularly formation of the head region that generates the electrical impulses that induce heart contraction. The present study aimed to confirm the effects of TBX18 on biological pacemaker differentiation of rat BMSCs. Flow cytometry was used to identify the surface markers of BMSCs, in order to acquire pure mesenchymal stem cells...
November 16, 2017: International Journal of Molecular Medicine
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