The Promise of Induced Pluripotent Stem Cell–Derived Cardiomyocytes to Treat Heart Failure

Lancaster, Jordan J.; Koevary, Jen Watson; Chinyere, Ikeotunye Royal; Goldman, Steven

doi:10.1161/circheartfailure.118.005425

Cited by 5 publications

(6 citation statements)

References 19 publications

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“…iPSC‐CMs have also been developed as a potential allogenic CT and tested in nonhuman primates, displaying electrical integration with the host heart, leading to improvement of contractile function after 4 weeks with no significant immune rejection 32 . These encouraging preclinical results supported clinical trials to determine the safety to iPSC‐CM transplantation as cell sheets 33,34 …”

Section: Introductionmentioning

confidence: 93%

“…and al., enhanced ventricular remodeling and functional capacity 24 MSCs-CSCs e Aut., decreased infarct size, improved cardiac function via paracrine effects 25 Aut., scar size reduction 26 Al., scar size reduction and systolic function recovery 27 -Aut., undergoing 28 iPSCs-CMs f Aut., improved left ventricular function 29 Al., improved left ventricular function 30 Al., improved contractile function 31 Al., contractile function improvement 32 Al. 33 and Aut., 34 transplanted in cell sheets, undergoing hESC-CMs g Al., CMs survived and engrafted to the heart for weeks 35,36 Al., angiogenesis and ECM h formation 37 Al., adequate engraftment 38 Al., enhanced remuscularization 39 Al., improvement of left ventricular function 40 Al, transplanted in fibrin patch, improved systolic function 41 Abbreviations: BMC, bone marrow cell; CMs, cardiomyocytes; CT, cell therapy; ECM, extracellular matrix; hESC, human embryonic stem cell; iPSCs, induced pluripotent cells; MSC, mesenchymal stromal cell.…”

Section: Myoblastsmentioning

confidence: 99%

“…32 These encouraging preclinical results supported clinical trials to determine the safety to iPSC-CM transplantation as cell sheets. 33,34 In vivo CT studies to treat cardiac ischemic injury from hypoxia have postulated a wide range of possible regenerative mechanisms that are linked to cell type and origin (autologous or allogenic). These include functional integration with recipient CMs, activating the growth and differentiation of endogenous CSCs, 65,66 trans-differentiation of transplanted SCs into new CMs and/or endothelial cells, metalloprotease-driven cardiac tissue matrix remodeling, as well as via the recruitment of white blood cells to repair micro-vessels.…”

Section: Significance Statementmentioning

confidence: 99%

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Cell augmentation strategies for cardiac stem cell therapies

Cruz-Samperio

Jordan

Perriman

2021

Stem Cells Translational Medicine

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Myocardial infarction (MI) has been the primary cause of death in developed countries, resulting in a major psychological and financial burden for society. Current treatments for acute MI are directed toward rapid restoration of perfusion to limit damage to the myocardium, rather than promoting tissue regeneration and subsequent contractile function recovery. Regenerative cell therapies (CTs), in particular those using multipotent stem cells (SCs), are in the spotlight for treatment post-MI.Unfortunately, the efficacy of CTs is somewhat limited by their poor long-term viability, homing, and engraftment to the myocardium. In response, a range of novel SCbased technologies are in development to provide additional cellular modalities, bringing CTs a step closer to the clinic. In this review, the current landscape of emerging CTs and their augmentation strategies for the treatment post-MI are discussed. In doing so, we highlight recent advances in cell membrane reengineering via genetic modifications, recombinant protein immobilization, and the utilization of soft biomimetic scaffold interfaces.

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Section: Introductionmentioning

confidence: 93%

Section: Myoblastsmentioning

confidence: 99%

Section: Significance Statementmentioning

confidence: 99%

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Cell augmentation strategies for cardiac stem cell therapies

Cruz-Samperio

Jordan

Perriman

2021

Stem Cells Translational Medicine

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“…Direct reprogramming methodologies could significantly lower the tumor formation risk, based on transcriptional factors such as genetic or small chemical molecules that avoid the pluripotent state. In addition, because of the wider choice of cell sources, the reprogramming technique could further contribute to the development of autologous cell transplantation for heart disease treatment, which could reduce the concern of immune rejection, as was mentioned in the previous sections [ 74 ].…”

Section: Cardiac Reprogramming For Heart Regenerationmentioning

confidence: 99%

Advances in Cellular Reprogramming-Based Approaches for Heart Regenerative Repair

Liang

Paul

et al. 2022

Cells

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Continuous loss of cardiomyocytes (CMs) is one of the fundamental characteristics of many heart diseases, which eventually can lead to heart failure. Due to the limited proliferation ability of human adult CMs, treatment efficacy has been limited in terms of fully repairing damaged hearts. It has been shown that cell lineage conversion can be achieved by using cell reprogramming approaches, including human induced pluripotent stem cells (hiPSCs), providing a promising therapeutic for regenerative heart medicine. Recent studies using advanced cellular reprogramming-based techniques have also contributed some new strategies for regenerative heart repair. In this review, hiPSC-derived cell therapeutic methods are introduced, and the clinical setting challenges (maturation, engraftment, immune response, scalability, and tumorigenicity), with potential solutions, are discussed. Inspired by the iPSC reprogramming, the approaches of direct cell lineage conversion are merging, such as induced cardiomyocyte-like cells (iCMs) and induced cardiac progenitor cells (iCPCs) derived from fibroblasts, without induction of pluripotency. The studies of cellular and molecular pathways also reveal that epigenetic resetting is the essential mechanism of reprogramming and lineage conversion. Therefore, CRISPR techniques that can be repurposed for genomic or epigenetic editing become attractive approaches for cellular reprogramming. In addition, viral and non-viral delivery strategies that are utilized to achieve CM reprogramming will be introduced, and the therapeutic effects of iCMs or iCPCs on myocardial infarction will be compared. After the improvement of reprogramming efficiency by developing new techniques, reprogrammed iCPCs or iCMs will provide an alternative to hiPSC-based approaches for regenerative heart therapies, heart disease modeling, and new drug screening.

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“…78,79 These materials allow for ways to develop more translatable therapies that can enhance vasculogenesis in the heart through soft biomaterials such as shear-thinning hydrogels, cardiac patches, and cell sheets. [80][81][82] Moreover, developing matrix-based strategies for injectable hydrogels could modulate inflammatory and reparative signals. Recently, Ventrix, a cardiac ECM hydrogel derived from decellularized porcine myocardium, showed great potential for injectable biomaterials after its phase 1 clinical trial (NCT02305602) in heart failure patients.…”

Section: Recent Advances In Engineered Cardiac Matrices For Ischemic Heart Repairmentioning

confidence: 99%

Bidirectional Relationship Between Cardiac Extracellular Matrix and Cardiac Cells in Ischemic Heart Disease

et al. 2021

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Ischemic heart diseases (IHDs), including myocardial infarction and cardiomyopathies, are a leading cause of mortality and morbidity worldwide. Cardiac-derived stem and progenitor cells have shown promise as a therapeutic for IHD but are limited by poor cell survival, limited retention, and rapid washout. One mechanism to address this is to encapsulate the cells in a matrix or three-dimensional construct, so as to provide structural support and better mimic the cells' physiological microenvironment during administration. More specifically, the extracellular matrix (ECM), the native cellular support network, has been a strong candidate for this purpose. Moreover, there is a strong consensus that the ECM and its residing cells, including cardiac stem cells, have a constant interplay in response to tissue development, aging, disease progression, and repair. When externally stimulated, the cells and ECM work together to mutually maintain the local homeostasis by initially altering the ECM composition and stiffness, which in turn alters the cellular response and behavior. Given this constant interplay, understanding the mechanism of bidirectional cell-ECM interaction is essential to develop better cell implantation matrices to enhance cell engraftment and cardiac tissue repair. This review summarizes current understanding in the field, elucidating the signaling mechanisms between cardiac ECM and residing cells in response to IHD onset. Furthermore, this review highlights recent advances in native ECM-mimicking cardiac matrices as a platform for modulating cardiac cell behavior and inducing cardiac repair.

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The Promise of Induced Pluripotent Stem Cell–Derived Cardiomyocytes to Treat Heart Failure

Cited by 5 publications

References 19 publications

Cell augmentation strategies for cardiac stem cell therapies

Cell augmentation strategies for cardiac stem cell therapies

Advances in Cellular Reprogramming-Based Approaches for Heart Regenerative Repair

Bidirectional Relationship Between Cardiac Extracellular Matrix and Cardiac Cells in Ischemic Heart Disease

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