Optimizing the Use of iPSC-CMs for Cardiac Regeneration in Animal Models

Bizy, Alexandra; Klos, Matthew

doi:10.3390/ani10091561

Cited by 10 publications

(11 citation statements)

References 215 publications

(367 reference statements)

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“…The feasibility of this approach has been shown in preclinical animal models. Intramyocardial injections of iPSC-CMs affect ejection fraction (PV-diagrams), cardiac wall thickness (histology), demonstrate epicardial-synchronous excitation (optical mapping) [ 2 , 3 , 4 , 5 , 6 , 7 ] However, electrocardiography (ECG) reveals regular engraftment arrhythmias (EAs), including transient ventricular tachyarrhythmias occurring 4–21 days after injection [ 3 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Polymer Kernels as Compact Carriers for Suspended Cardiomyocytes

et al. 2022

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Induced pluripotent stem cells (iPSCs) constitute a potential source of patient-specific human cardiomyocytes for a cardiac cell replacement therapy via intramyocardial injections, providing a major benefit over other cell sources in terms of immune rejection. However, intramyocardial injection of the cardiomyocytes has substantial challenges related to cell survival and electrophysiological coupling with recipient tissue. Current methods of manipulating cell suspensions do not allow one to control the processes of adhesion of injected cells to the tissue and electrophysiological coupling with surrounding cells. In this article, we documented the possibility of influencing these processes using polymer kernels: biocompatible fiber fragments of subcellular size that can be adsorbed to a cell, thereby creating the minimum necessary adhesion foci to shape the cell and provide support for the organization of the cytoskeleton and the contractile apparatus prior to adhesion to the recipient tissue. Using optical excitation markers, the restoration of the excitability of cardiomyocytes in suspension upon adsorption of polymer kernels was shown. It increased the likelihood of the formation of a stable electrophysiological coupling in vitro. The obtained results may be considered as a proof of concept that the stochastic engraftment process of injected suspension cells can be controlled by smart biomaterials.

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Section: Introductionmentioning

confidence: 99%

Polymer Kernels as Compact Carriers for Suspended Cardiomyocytes

et al. 2022

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“…In terms of the delivery route, intravenous injection, intramyocardial injection, and transplantation of engineered heart tissue/sheets are the major approaches for utilizing iPSC-CMs [ 39 ]. Most of these approaches have demonstrated a certain level of heart function improvement under various heart disease models [ 20 , 40 ].…”

Section: Challenges For Usage Of Ipsc-derived Cells In Heart Disease ...mentioning

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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“…Therefore, increasing research attention has been focused on the in vitro differentiation of iPSCs in the laboratory setting, to obtain the desired cell type, which can then be applied to the patient. Notably, the differentiation of murine and human iPSCs into cardiomyocytes (iPSC-CMs) has been extensively described and is now standard practice in laboratories worldwide [ 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 ].…”

Section: Ipsc Generation and Cardiac Differentiationmentioning

confidence: 99%

iPSC Therapy for Myocardial Infarction in Large Animal Models: Land of Hope and Dreams

2021

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Myocardial infarction is the main driver of heart failure due to ischemia and subsequent cell death, and cell-based strategies have emerged as promising therapeutic methods to replace dead tissue in cardiovascular diseases. Research in this field has been dramatically advanced by the development of laboratory-induced pluripotent stem cells (iPSCs) that harbor the capability to become any cell type. Like other experimental strategies, stem cell therapy must meet multiple requirements before reaching the clinical trial phase, and in vivo models are indispensable for ensuring the safety of such novel therapies. Specifically, translational studies in large animal models are necessary to fully evaluate the therapeutic potential of this approach; to empirically determine the optimal combination of cell types, supplementary factors, and delivery methods to maximize efficacy; and to stringently assess safety. In the present review, we summarize the main strategies employed to generate iPSCs and differentiate them into cardiomyocytes in large animal species; the most critical differences between using small versus large animal models for cardiovascular studies; and the strategies that have been pursued regarding implanted cells’ stage of differentiation, origin, and technical application.

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Optimizing the Use of iPSC-CMs for Cardiac Regeneration in Animal Models

Cited by 10 publications

References 215 publications

Polymer Kernels as Compact Carriers for Suspended Cardiomyocytes

Polymer Kernels as Compact Carriers for Suspended Cardiomyocytes

Advances in Cellular Reprogramming-Based Approaches for Heart Regenerative Repair

iPSC Therapy for Myocardial Infarction in Large Animal Models: Land of Hope and Dreams

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