scholarly journals Electrical Stimulation Enhances Cardiac Differentiation of Human Induced Pluripotent Stem Cells for Myocardial Infarction Therapy

2018 ◽  
Vol 28 (5) ◽  
pp. 371-384 ◽  
Author(s):  
Ruilian Ma ◽  
Jialiang Liang ◽  
Wei Huang ◽  
Linlin Guo ◽  
Wenfeng Cai ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Electrical Stimulation ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cardiac Differentiation ◽  
Induced Pluripotent

scholarly journals Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Damián Hernández ◽  
Rodney Millard ◽  
Priyadharshini Sivakumaran ◽  
Raymond C. B. Wong ◽  
Duncan E. Crombie ◽  
...  
Keyword(s):  
Stem Cells ◽  
Electrical Stimulation ◽  
Induced Pluripotent Stem Cells ◽  
Cell Line ◽  
Pluripotent Stem Cells ◽  
Embryoid Bodies ◽  
Cardiac Differentiation ◽  
Dependent Manner ◽  
Human Ipscs ◽  
Induced Pluripotent

Background.Human induced pluripotent stem cells (iPSCs) are an attractive source of cardiomyocytes for cardiac repair and regeneration. In this study, we aim to determine whether acute electrical stimulation of human iPSCs can promote their differentiation to cardiomyocytes.Methods. Human iPSCs were differentiated to cardiac cells by forming embryoid bodies (EBs) for 5 days. EBs were then subjected to brief electrical stimulation and plated down for 14 days.Results. In iPS(Foreskin)-2 cell line, brief electrical stimulation at 65 mV/mm or 200 mV/mm for 5 min significantly increased the percentage of beating EBs present by day 14 after plating. Acute electrical stimulation also significantly increased the cardiac gene expression ofACTC1,TNNT2,MYH7, andMYL7. However, the cardiogenic effect of electrical stimulation was not reproducible in another iPS cell line, CERA007c6. Beating EBs from control and electrically stimulated groups expressed various cardiac-specific transcription factors and contractile muscle markers. Beating EBs were also shown to cycle calcium and were responsive to the chronotropic agents, isoproterenol and carbamylcholine, in a concentration-dependent manner.Conclusions. Our results demonstrate that brief electrical stimulation can promote cardiac differentiation of human iPS cells. The cardiogenic effect of brief electrical stimulation is dependent on the cell line used.

scholarly journals Rabbit induced pluripotent stem cells retain capability of in vitro cardiac differentiation

2019 ◽  
Vol 68 (1) ◽  
pp. 35-47 ◽  
Author(s):  
Praopilas Phakdeedindan ◽  
Piyathip Setthawong ◽  
Narong Tiptanavattana ◽  
Sasitorn Rungarunlert ◽  
Praewphan Ingrungruanglert ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cardiac Differentiation ◽  
Induced Pluripotent

Cardiac differentiation at an initial low density of human-induced pluripotent stem cells

2018 ◽  
Vol 54 (7) ◽  
pp. 513-522 ◽  
Author(s):  
Minh Nguyen Tuyet Le ◽  
Mika Takahi ◽  
Kenshiro Maruyama ◽  
Akira Kurisaki ◽  
Kiyoshi Ohnuma
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cardiac Differentiation ◽  
Low Density ◽  
Induced Pluripotent

Abstract 341: Transplantation of Cardiac Tissue Sheets Including Defined Cardiovascular Cell Populations Differentiated from Human-Induced Pluripotent Stem Cells Ameliorates Cardiac Dysfunction After Subacute Myocardial Infarction

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Hidetoshi Masumoto ◽  
Tadashi Ikeda ◽  
Tatsuya Shimizu ◽  
Teruo Okano ◽  
Ryuzo Sakata ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cardiac Dysfunction ◽  
Cardiac Tissue ◽  
Vascular Endothelial Cell ◽  
Cell Populations ◽  
Cardiac Cell ◽  
Induced Pluripotent

BACKGROUNDS: To realize cardiac regeneration with human induced pluripotent stem cells (hiPSCs), efficient differentiation from hiPSCs to defined cardiac cell populations (cardiomyocytes [CMs]/ endothelial cells [ECs]/ vascular mural cells [MCs]), and transplantation technique for fair engraftment are required. Recently, we reported that mouse ES cell-derived cardiac tissue sheet transplantation to rat myocardial infarction (MI) model ameliorated cardiac function after MI (Stem Cells, in press). Here we tried to extend this technique to hiPSCs. METHODS & RESULTS: We have reported an efficient cardiomyocyte differentiation protocol based on a monolayer culture (PLoS One, 2011), in which cardiac troponin-T (cTnT)-positive CMs robustly appeared with 50-80% efficiency. In this study, we further modified the protocol to induce vascular cells (ECs/MCs) together with CMs by vascular endothelial cell growth factor supplementation, resulted in proportional differentiation of cTnT+-CMs (62.7±11.7% of total cells), VE-cadherin+-ECs (7.8±4.9%) and PDGFRb+-MCs (18.2±11.0%) at differentiation day 15 (n=12). Then, these cells were transferred onto temperature-responsive culture dishes (UpCell dishes; CellSeed, Tokyo, Japan) to form cardiac tissue sheets including defined cardiac populations. After 4 days of culture, we successfully collected self-pulsating cardiac tissue sheets with 7.0×10 5 ±2.3 (n=12) of cells consisted of CMs (46.9±15.9% of total cells), ECs (4.1±3.7%), and MCs (22.5±15.7%). Three-layered hiPSC-derived cardiac sheets were transplanted to a MI model of athymic rat heart one week after MI. In transplantation group, echocardiogram showed a significant improvement of systolic function of left ventricle (fractional shortening: 22.6±5.0 vs 36.5±8.0%, p<0.001, n=20) and a decrease in akinetic length (20.8±9.7 vs 2.5±7.7%, p<0.001, n=20) (pre-treatment vs 4weeks after transplantation). We also succeeded in generation of larger sheets (1.6 inch diameter) with the same method. CONCLUTIONS: Transplantation of hiPSC-derived cardiac tissue sheets significantly ameliorates cardiac dysfunction after MI. Thus, we developed a valuable technological basis for hiPSC-based cardiac cell therapy.

Abstract 109: The Effect Of Cell Sex On Cardiogenic Differentiation Of Human Induced Pluripotent Stem Cells And Their Maturation Processes

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Morteza Mahmoudi ◽  
Phillip C Yang ◽  
Vahid Serpooshan ◽  
Parisa Abadi ◽  
Mahyar Heydarpour
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Cardiac Differentiation ◽  
Patient Specific ◽  
Patterned Substrates ◽  
Male And Female ◽  
Induced Pluripotent ◽  
Cardiogenic Differentiation

Introduction: Patient-specific human induced pluripotent stem cells (hiPSC)-derived cardiomyocytes (CMs) are increasingly used for in vitro disease modeling and drug screening, as well in vivo regenerative therapies. The cardiac differentiation efficacy of hiPSCs, together with the maturation level of generated CMs, are critical factors in achieving the required numbers of functional patient-specific cardiac muscle cells for clinical applications. Although extensive studies have improved the efficacy of differentiation and maturation processes, the role of cell sex in these processes has not been fully investigated. Hypothesis: Cell sex affects i) the cardiogenic differentiation efficacy of hiPSCs; and ii) maturation processes of hiPSC-CMs. Methods and Results: We have successfully and reproducibly fabricated patterned substrates recapitulating the 3D shape of mature CMs, using photolithography approaches, and demonstrated that the substrate could i) accelerate the differentiation of hiPSCs to CMs, and ii) facilitate maturation and functionality of immature hiPSC-CMs. Male and female hiPSCs, derived from human amniotic mesenchymal stem cells of male and female fetuses, were cultured onto flat (control) vs. patterned substrates. A total of 400 differentiation assays were conducted, 200 per each cell sex, on the flat ( n = 100) and patterned ( n = 100) substrates. A chemically defined approach was used to differentiate the cells toward CMs. On the flat (conventional) substrates, 59% of batches of male and 87% of batches of female hiPSCs differentiated into beating CMs (> 80%). On the patterned substrates, these numbers changed to 83% and 94% of successful differentiations for male and female hiPSCs, respectively. These results indicate the significant effect of substrate-mediated topographical cues on the cardiac differentiation yield of stem cells and the batch-to-batch variation. On both substrate types, female cells demonstrated significantly higher success rates of cardiac differentiation compared to the male cells. In addition, the CMs produced on the patterned substrates demonstrated higher purity than those created on the flat substrates both for male and female cells. Quantitative polymerase chain reaction (qPCR) was used to probe the male and female cell differences in expression of genes related to cardiac maturity, contractility, and Ca 2+ transport (TNNT2, MYH6, MYH7, and CACNA1c) and the outcomes revealed substantially greater expression levels of the maturation genes in differentiated female CMs cultured on the patterned substrates compared to the male cells. Conclusions: These results indicate that male and female hiPSCs and hiPSC-CMs respond differently to the identical substrates in terms of their differentiation and maturation efficacies.

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