Translation of Human-Induced Pluripotent Stem Cells

Sayed, Nazish; Li, Chun; Wu, Joseph C.

doi:10.1016/j.jacc.2016.01.083

Cited by 234 publications

(108 citation statements)

References 176 publications

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“…Alternative preclinical models involve the use of human ex vivo cultured cardiac tissues and human pluripotent stem cell (PSC)-derived cardiomyocytes, which theoretically should be suitable for performing in vitro proof-of-principle studies 211 .…”

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confidence: 99%

Therapeutic approaches for cardiac regeneration and repair

2018

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Ischaemic heart disease is a leading cause of death worldwide. Injury to the heart is followed by loss of the damaged cardiomyocytes, which are replaced with fibrotic scar tissue. Depletion of cardiomyocytes results in decreased cardiac contraction, which leads to pathological cardiac dilatation, additional cardiomyocyte loss, and mechanical dysfunction, culminating in heart failure. This sequential reaction is defined as cardiac remodelling. Many therapies have focused on preventing the progressive process of cardiac remodelling to heart failure. However, after patients have developed end-stage heart failure, intervention is limited to heart transplantation. One of the main reasons for the dramatic injurious effect of cardiomyocyte loss is that the adult human heart has minimal regenerative capacity. In the past 2 decades, several strategies to repair the injured heart and improve heart function have been pursued, including cellular and noncellular therapies. In this Review, we discuss current therapeutic approaches for cardiac repair and regeneration, describing outcomes, limitations, and future prospects of preclinical and clinical trials of heart regeneration. Substantial progress has been made towards understanding the cellular and molecular mechanisms regulating heart regeneration, offering the potential to control cardiac remodelling and redirect the adult heart to a regenerative state.

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confidence: 99%

Therapeutic approaches for cardiac regeneration and repair

2018

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“…The most advantageous feature of human iPS cells in drug discovery is the capacity of these cells to recapitulate the donor’s phenotype in vitro, thus ushering in an era of “clinical trials in a dish” [139]. The growing number of human iPS cell banks that are being established worldwide confirms various research organizations’ unflagging interest in iPS cells.…”

Section: Future Perspectivesmentioning

confidence: 99%

Translational Prospects and Challenges in Human Induced Pluripotent Stem Cell Research in Drug Discovery

Hashimoto

Czysz

2016

Cells

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Despite continuous efforts to improve the process of drug discovery and development, achieving success at the clinical stage remains challenging because of a persistent translational gap between the preclinical and clinical settings. Under these circumstances, the discovery of human induced pluripotent stem (iPS) cells has brought new hope to the drug discovery field because they enable scientists to humanize a variety of pharmacological and toxicological models in vitro. The availability of human iPS cell-derived cells, particularly as an alternative for difficult-to-access tissues and organs, is increasing steadily; however, their use in the field of translational medicine remains challenging. Biomarkers are an essential part of the translational effort to shift new discoveries from bench to bedside as they provide a measurable indicator with which to evaluate pharmacological and toxicological effects in both the preclinical and clinical settings. In general, during the preclinical stage of the drug development process, in vitro models that are established to recapitulate human diseases are validated by using a set of biomarkers; however, their translatability to a clinical setting remains problematic. This review provides an overview of current strategies for human iPS cell-based drug discovery from the perspective of translational research, and discusses the importance of early consideration of clinically relevant biomarkers.

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“…There are several significant limitations to progress in studying cardiac disorders, including the lack of relevant tissue samples, inability to study human cardiomyocytes longitudinally, and lack of a patient-specific drug testing platform 1 . Traditionally, researchers have relied on cell-based assays or animal models to understand disease progression and develop therapeutic interventions 2 .…”

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confidence: 99%

“…Additionally, iPSCs are patient-specific, allowing them to more faithfully recapitulate the genotype encoded by original donor; this enables researchers to understand disease mechanisms at an individual patient level, potentially allowing screening of individual drugs for efficacy and toxicity. For these reasons, a precise prediction of each patient’s unique responses to different drugs is now within reach under the iPSC-based model as it becomes an increasingly valuable drug screening tool to guide clinical pharmacotherapy 1, 4, 8, 9 (Figure 1). …”

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confidence: 99%