scholarly journals Transplantation of Human Pluripotent Stem Cell-Derived Cardiomyocytes for Cardiac Regenerative Therapy

2021 ◽  
Vol 8 ◽  
Author(s):  
Sophia E. Silver ◽  
Ryan W. Barrs ◽  
Ying Mei
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cardiac Tissue ◽  
Therapeutic Potential ◽  
Cardiac Injury ◽  
Human Cardiomyocytes ◽  
Heart Repair ◽  
Recent Developments ◽  
Successful Transplantation ◽  
Induced Pluripotent

Cardiovascular disease is the leading cause of death worldwide and bears an immense economic burden. Late-stage heart failure often requires total heart transplantation; however, due to donor shortages and lifelong immunosuppression, alternative cardiac regenerative therapies are in high demand. Human pluripotent stem cells (hPSCs), including human embryonic and induced pluripotent stem cells, have emerged as a viable source of human cardiomyocytes for transplantation. Recent developments in several mammalian models of cardiac injury have provided strong evidence of the therapeutic potential of hPSC-derived cardiomyocytes (hPSC-CM), showing their ability to electromechanically integrate with host cardiac tissue and promote functional recovery. In this review, we will discuss recent developments in hPSC-CM differentiation and transplantation strategies for delivery to the heart. We will highlight the mechanisms through which hPSC-CMs contribute to heart repair, review major challenges in successful transplantation of hPSC-CMs, and present solutions that are being explored to address these limitations. We end with a discussion of the clinical use of hPSC-CMs, including hurdles to clinical translation, current clinical trials, and future perspectives on hPSC-CM transplantation.

scholarly journals Pharmacological response of human cardiomyocytes derived from virus-free induced pluripotent stem cells

2011 ◽  
Vol 91 (4) ◽  
pp. 577-586 ◽  
Author(s):  
Ashish Mehta ◽  
Ying Ying Chung ◽  
Alvin Ng ◽  
Fahamy Iskandar ◽  
Shirhan Atan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Human Cardiomyocytes ◽  
Pharmacological Response ◽  
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.

Cardiomyocyte differentiation of pluripotent stem cells and their use as cardiac disease models

2011 ◽  
Vol 434 (1) ◽  
pp. 25-35 ◽  
Author(s):  
Cheryl Dambrot ◽  
Robert Passier ◽  
Douwe Atsma ◽  
Christine L. Mummery
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cardiac Disease ◽  
Coming Of Age ◽  
Embryonic Stem ◽  
Daily Basis ◽  
Human Cardiomyocytes ◽  
Human Ipscs ◽  
Induced Pluripotent ◽  
Exciting Area

More than 10 years after their first isolation, human embryonic stem cells are finally ‘coming of age’ in research and biotechnology applications as protocols for their differentiation and undifferentiated expansion in culture become robust and scalable, and validated commercial reagents become available. Production of human cardiomyocytes is now feasible on a daily basis for many laboratories with tissue culture expertise. An additional recent surge of interest resulting from the first production of human iPSCs (induced pluripotent stem cells) from somatic cells of patients now makes these technologies of even greater importance since it is likely that (genetic) cardiac disease phenotypes can be captured in the cardiac derivatives of these cells. Although cell therapy based on replacing cardiomyocytes lost or dysfunctional owing to cardiac disease are probably as far away as ever, biotechnology and pharmaceutical applications in safety pharmacology and drug discovery will probably impact this clinical area in the very near future. In the present paper, we review the cutting edge of this exciting area of translational research.

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