scholarly journals Cardiomyocyte Maturation

2020 ◽  
Vol 126 (8) ◽  
pp. 1086-1106 ◽  
Author(s):  
Yuxuan Guo ◽  
William T. Pu
Keyword(s):  
Stem Cell ◽  
Heart Development ◽  
Pluripotent Stem Cell ◽  
Therapeutic Strategies ◽  
Antagonistic Effect ◽  
Regulatory Mechanisms ◽  
Potential Contribution ◽  
Significant Progress ◽  
Cellular Events ◽  
Novel Therapeutic Strategies

Maturation is the last phase of heart development that prepares the organ for strong, efficient, and persistent pumping throughout the mammal’s lifespan. This process is characterized by structural, gene expression, metabolic, and functional specializations in cardiomyocytes as the heart transits from fetal to adult states. Cardiomyocyte maturation gained increased attention recently due to the maturation defects in pluripotent stem cell–derived cardiomyocyte, its antagonistic effect on myocardial regeneration, and its potential contribution to cardiac disease. Here, we review the major hallmarks of ventricular cardiomyocyte maturation and summarize key regulatory mechanisms that promote and coordinate these cellular events. With advances in the technical platforms used for cardiomyocyte maturation research, we expect significant progress in the future that will deepen our understanding of this process and lead to better maturation of pluripotent stem cell–derived cardiomyocyte and novel therapeutic strategies for heart disease.

scholarly journals Insights to Heart Development and Cardiac Disease Models Using Pluripotent Stem Cell Derived 3D Organoids

2021 ◽  
Vol 9 ◽  
Author(s):  
Jeremy Kah Sheng Pang ◽  
Beatrice Xuan Ho ◽  
Woon-Khiong Chan ◽  
Boon-Seng Soh
Keyword(s):  
Cardiac Disease ◽  
Heart Development ◽  
Pluripotent Stem Cell ◽  
3D Models ◽  
Cardiac Diseases ◽  
Significant Progress ◽  
Fundamental Parameters ◽  
Developing Heart

Medical research in the recent years has achieved significant progress due to the increasing prominence of organoid technology. Various developed tissue organoids bridge the limitations of conventional 2D cell culture and animal models by recapitulating in vivo cellular complexity. Current 3D cardiac organoid cultures have shown their utility in modelling key developmental hallmarks of heart organogenesis, but the complexity of the organ demands a more versatile model that can investigate more fundamental parameters, such as structure, organization and compartmentalization of a functioning heart. This review will cover the prominence of cardiac organoids in recent research, unpack current in vitro 3D models of the developing heart and look into the prospect of developing physiologically appropriate cardiac organoids with translational applicability. In addition, we discuss some of the limitations of existing cardiac organoid models in modelling embryonic development of the heart and manifestation of cardiac diseases.

Abstract 477: Modeling the Effect of TBX5 Downregulation on Human Atrial Conduction Using Induced Pluripotent Stem Cell-derived Cardiomyocytes

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Sherri M Biendarra-tiegs ◽  
Sergey Yechikov ◽  
Laura Houshmand ◽  
R. E Gonzalez ◽  
Zhi Hong Lu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Conduction Velocity ◽  
Heart Development ◽  
Pluripotent Stem Cell ◽  
Microelectrode Array ◽  
Association Studies ◽  
Induced Pluripotent Stem Cell ◽  
Immunofluorescent Staining ◽  
Genome Wide Association Studies ◽  
Induced Pluripotent

Atrial fibrillation (AF) poses a notable healthcare burden due to a high incidence in the increasing population over age 65 and limitations of current treatment approaches. One challenge to effectively treat AF is patient-to-patient heterogeneity in the underlying mechanisms of disease. Therefore, a better understanding of AF pathogenesis and more personalized approaches to therapy could reduce risk of side effects and improve therapeutic efficacy. Genome wide association studies (GWAS) have revealed several candidate genes for AF including TBX5 , which encodes for a transcription factor involved in heart development. While work in animal models suggests that loss of TBX5 promotes atrial arrythmias, experimental evidence in human cells is lacking. We created an in vitro model of human atrial conduction using day 60+ induced pluripotent stem cell-derived atrial-like cardiomyocytes (iPSC-aCMs) differentiated from three established healthy iPSC lines. Over 90% atrial-like purity (out of 350+ alpha-actinin positive cardiomyocytes) could be achieved based on MLC2v-/MLC2a+ immunofluorescent staining. TBX5 knockdown via esiRNA resulted in downregulation of genes related to conduction velocity ( GJA5 and SCN5A ), consistent with an enhanced risk of AF. Single cell optical electrophysiology demonstrated slightly reduced action potential amplitude and upstroke velocity for TBX5 knockdown cells versus GFP esiRNA controls, suggesting a functional effect of SCN5A downregulation. Additionally, microelectrode array studies have revealed a trend towards slowed conduction velocity with TBX5 knockdown compared to GFP esiRNA controls (13.1±3.0 cm/s vs 17.0±3.8 cm/s respectively). By further investigating the functional effects of modulating transcription factors such as TBX5 in iPSC-aCMs, our results provide enhanced insight into the regulation of atrial conduction and identify potential AF-related pathways for therapeutic targeting.

scholarly journals Stem Cell Transplantation in Cardiovascular Disease: An Update

2012 ◽  
Vol 40 (3) ◽  
pp. 833-838 ◽  
Author(s):  
M Teng ◽  
Z Geng ◽  
L Huang ◽  
X Zhao
Keyword(s):  
Stem Cell ◽  
Cardiovascular Diseases ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Phase 1 ◽  
Cell Types ◽  
Therapeutic Strategies ◽  
Routes Of Administration ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Despite the development of novel therapeutic strategies, cardiovascular diseases remain the main cause of morbidity and mortality worldwide. Many phase 1 and 2 clinical trials have reported the safety, feasibility and promising potential of stem cell transplantation, however, the optimal cell types, timing of infusion, cell dosage and routes of administration remain to be determined. This paper reviews the findings of various clinical studies and discusses the challenges facing the delivery of stem cell therapy in cardiovascular diseases.

scholarly journals Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes as a Model for Heart Development and Congenital Heart Disease

2015 ◽  
Vol 11 (5) ◽  
pp. 710-727 ◽  
Author(s):  
Michelle J. Doyle ◽  
Jamie L. Lohr ◽  
Christopher S. Chapman ◽  
Naoko Koyano-Nakagawa ◽  
Mary G. Garry ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Stem Cell ◽  
Heart Disease ◽  
Heart Development ◽  
Pluripotent Stem Cell ◽  
Congenital Heart ◽  
Induced Pluripotent Stem Cell ◽  
Induced Pluripotent

scholarly journals Microscopic studies on severing properties of actin-binding protein: its potential use in therapeutic treatment of actin-rich inclusions

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Han-ul Kim ◽  
Anahita Vispi Bharda ◽  
Jeong Chan Moon ◽  
Dooil Jeoung ◽  
Jeong Min Chung ◽  
...  
Keyword(s):  
Therapeutic Strategies ◽  
Regulatory Mechanisms ◽  
Actin Binding ◽  
Cellular Processes ◽  
Transmission Electron ◽  
Microscopic Studies ◽  
Molecular Aspects ◽  
Novel Therapeutic Strategies ◽  
Cytoskeletal System ◽  
Potential Use

AbstractActin is an important unit of the cytoskeletal system, involved in many cellular processes including cell motility, signaling, and intracellular trafficking. Various studies have been undertaken to understand the regulatory mechanisms pertaining actin functions, especially the ones controlled by actin-binding proteins. However, not much has been explored about the molecular aspects of these proteins implicated in various diseases. In this study, we aimed to demonstrate the molecular properties of gelsolin, an actin-severing protein on the disassembly of the aggregation of actin-rich intracellular inclusions, Hirano body. We observed a decreasing tendency of actin aggregation by co-sedimentation assay and transmission electron microscopy in the presence of gelsolin. Therefore, we provide suggestive evidence for the use of actin-severing protein in novel therapeutic strategies for neurodegenerative conditions.

scholarly journals Current Concepts of Stem Cell Therapy for Chronic Spinal Cord Injury

2021 ◽  
Vol 22 (14) ◽  
pp. 7435
Author(s):  
Hidenori Suzuki ◽  
Takashi Sakai
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Therapeutic Strategies ◽  
Chronic Spinal Cord Injury ◽  
Cord Injury ◽  
Neural Stem Progenitor Cells ◽  
Financial Burdens ◽  
Novel Therapeutic Strategies

Chronic spinal cord injury (SCI) is a catastrophic condition associated with significant neurological deficit and social and financial burdens. It is currently being managed symptomatically with no real therapeutic strategies available. In recent years, a number of innovative regenerative strategies have emerged and have been continuously investigated in clinical trials. In addition, several more are coming down the translational pipeline. Among ongoing and completed trials are those reporting the use of mesenchymal stem cells, neural stem/progenitor cells, induced pluripotent stem cells, olfactory ensheathing cells, and Schwann cells. The advancements in stem cell technology, combined with the powerful neuroimaging modalities, can now accelerate the pathway of promising novel therapeutic strategies from bench to bedside. Various combinations of different molecular therapies have been combined with supportive scaffolds to facilitate favorable cell–material interactions. In this review, we summarized some of the most recent insights into the preclinical and clinical studies using stem cells and other supportive drugs to unlock the microenvironment in chronic SCI to treat patients with this condition. Successful future therapies will require these stem cells and other synergistic approaches to address the persistent barriers to regeneration, including glial scarring, loss of structural framework, and immunorejection.

scholarly journals PPARdelta signaling activation improves metabolic and contractile maturation of human pluripotent stem cell-derived cardiomyocytes.

2021 ◽  
Author(s):  
Nadeera M Wickramasinghe ◽  
David Sachs ◽  
Bhavana Shewale ◽  
David M Gonzalez ◽  
Priyanka Dhanan-Krishnan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Heart Development ◽  
Regulatory Networks ◽  
Pluripotent Stem Cell ◽  
Disease Modeling ◽  
Acid Oxidation ◽  
Metabolic Switch ◽  
Ppar Signaling ◽  
Signaling Activation ◽  
Cardiac Maturation

Pluripotent stem cell-derived cardiomyocytes (PSC-CMs) provide an unprecedented opportunity to study human heart development and disease. A major caveat however is that they remain functionally and structurally immature in culture, limiting their potential for disease modeling and regenerative approaches. Here, we address the question of how different metabolic pathways can be modulated in order to induce efficient hPSC-CM maturation. We show that PPAR signaling acts in an isoform-specific manner to balance glycolysis and fatty acid oxidation (FAO). PPARD activation or inhibition results in efficient respective up- or down-regulation of the gene regulatory networks underlying FAO in hPSC-CMs. PPARD induction further increases mitochondrial and peroxisome content, enhances mitochondrial cristae formation and augments FAO flux. Lastly PPARD activation results in enhanced myofibril organization and improved contractility. Transient lactate exposure, commonly used in hPSC-CM purification protocols, induces an independent program of cardiac maturation, but when combined with PPARD activation equally results in a metabolic switch to FAO. In summary, we identify multiple axes of metabolic modifications of hPSC-CMs and a role for PPARD signaling in inducing the metabolic switch to FAO in hPSC-CMs. Our findings provide new and easily implemented opportunities to generate mature hPSC-CMs for disease modeling and regenerative therapy.

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