Molecular barriers to direct cardiac reprogramming

Vaseghi, Haley Ruth; Liu, Jiandong; Li, Qian

doi:10.1007/s13238-017-0402-x

Cited by 33 publications

(16 citation statements)

References 40 publications

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“…Each strategy has shown promising benefits but are also facing different technical challenges [22,23]. Many research progresses of direct cardiac reprogramming have been discussed in recently review articles [24,25,26]; in this article, we reviewed the newest discoveries of direct cardiac reprogramming, including cell cycle regulation, chemokine signaling, inflammatory immune signaling, and single-cell RNA-seq findings during reprogramming of induced cardiomyocyte-like cells (iCM), and incorporated a new understanding of matrifibrocytes during cardiac fibrotic remodeling to discuss future directions of translating this promising technology into clinical applications.…”

Section: Introductionmentioning

confidence: 99%

Ameliorating the Fibrotic Remodeling of the Heart through Direct Cardiac Reprogramming

Bektik¹,

Fu²

2019

Cells

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Coronary artery disease is the most common form of cardiovascular diseases, resulting in the loss of cardiomyocytes (CM) at the site of ischemic injury. To compensate for the loss of CMs, cardiac fibroblasts quickly respond to injury and initiate cardiac remodeling in an injured heart. In the remodeling process, cardiac fibroblasts proliferate and differentiate into myofibroblasts, which secrete extracellular matrix to support the intact structure of the heart, and eventually differentiate into matrifibrocytes to form chronic scar tissue. Discovery of direct cardiac reprogramming offers a promising therapeutic strategy to prevent/attenuate this pathologic remodeling and replace the cardiac fibrotic scar with myocardium in situ. Since the first discovery in 2010, many progresses have been made to improve the efficiency and efficacy of reprogramming by understanding the mechanisms and signaling pathways that are activated during direct cardiac reprogramming. Here, we overview the development and recent progresses of direct cardiac reprogramming and discuss future directions in order to translate this promising technology into an effective therapeutic paradigm to reverse cardiac pathological remodeling in an injured heart.

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Section: Introductionmentioning

confidence: 99%

Ameliorating the Fibrotic Remodeling of the Heart through Direct Cardiac Reprogramming

Bektik¹,

Fu²

2019

Cells

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“…In addition to clinical trials, considerable basic and translational research has been conducted with the aim of developing a cell transplantation-based treatment of heart failure. Several sources have been proposed for generating new cardiomyocyte cell sources, including embryonic stem cells (ESC), induced pluripotent stem cells (iPSC), mesenchymal stem cells, cardiac progenitor cells, and transdifferentiation of non-cardiomyocytes 7,[9][10][11][12] . Considerable effort has been made to overcome the roadblocks of cell transplant treatment.…”

Section: Cell Transplant Treatmentmentioning

confidence: 99%

“…Direct reprogramming of non-cardiomyocytes such as cardiac fibroblasts, is another strategy to generate new cardiomyocytes to restore cardiac function during HF. In vitro and in vivo animal studies indicate that a variety of signaling cocktails can convert cardiac fibroblasts into induced cardiomyocyte-like cells, which helps to reduce the cardiac scarring and improve cardiac function recovery after infarction, yet there are still numerous barriers to overcome before any clinical application should be considered 12 .…”

Section: Cell Transplant Treatmentmentioning

confidence: 99%

Stimulating Cardiogenesis as a Treatment for Heart Failure

Heallen

Kadow

Kim³

et al. 2019

Circulation Research

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Following myocardial injury, cardiomyocyte loss cannot be corrected by using currently available clinical treatments. In recent years, considerable effort has been made to develop cell-based cardiac repair therapies aimed at correcting for this loss. An exciting crop of recent studies reveal that inducing endogenous repair and proliferation of cardiomyocytes may be a viable option for regenerating injured myocardium. Here, we review current heart failure treatments, the state of cardiomyocyte renewal in mammals, and the molecular signals that stimulate cardiomyocyte proliferation. These signals include growth factors, intrinsic signaling pathways, microRNAs, and cell cycle regulators. Animal model cardiac regeneration studies reveal that modulation of exogenous and cell intrinsic signaling pathways can induce re-entry of adult cardiomyocytes into the cell cycle. Using direct myocardial injection, epicardial patch delivery or systemic administration of growth molecules, these studies show that inducing endogenous cardiomyocytes to self-renew is an exciting and promising therapeutic strategy to treat cardiac injury in humans.

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“…Most iCM generation techniques employ the use of virus-based strategies to deliver reprogramming factors, which raises safety concerns including endogenous gene disruption and insertional mutagenesis [ 109 ]. Investigators have tried to avoid this pitfall via nongenetic strategies that employ the use of small molecules to induce reprogramming [ 110 ].…”

Section: Direct Cardiac Reprogramming For Heart Regenerationmentioning

confidence: 99%

Strategies and Challenges to Improve Cellular Programming-Based Approaches for Heart Regeneration Therapy

Jiang

Liang

Huang

et al. 2020

IJMS

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Limited adult cardiac cell proliferation after cardiovascular disease, such as heart failure, hampers regeneration, resulting in a major loss of cardiomyocytes (CMs) at the site of injury. Recent studies in cellular reprogramming approaches have provided the opportunity to improve upon previous techniques used to regenerate damaged heart. Using these approaches, new CMs can be regenerated from differentiation of iPSCs (similar to embryonic stem cells), the direct reprogramming of fibroblasts [induced cardiomyocytes (iCMs)], or induced cardiac progenitors. Although these CMs have been shown to functionally repair infarcted heart, advancements in technology are still in the early stages of development in research laboratories. In this review, reprogramming-based approaches for generating CMs are briefly introduced and reviewed, and the challenges (including low efficiency, functional maturity, and safety issues) that hinder further translation of these approaches into a clinical setting are discussed. The creative and combined optimal methods to address these challenges are also summarized, with optimism that further investigation into tissue engineering, cardiac development signaling, and epigenetic mechanisms will help to establish methods that improve cell-reprogramming approaches for heart regeneration.

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Molecular barriers to direct cardiac reprogramming

Cited by 33 publications

References 40 publications

Ameliorating the Fibrotic Remodeling of the Heart through Direct Cardiac Reprogramming

Ameliorating the Fibrotic Remodeling of the Heart through Direct Cardiac Reprogramming

Stimulating Cardiogenesis as a Treatment for Heart Failure

Strategies and Challenges to Improve Cellular Programming-Based Approaches for Heart Regeneration Therapy

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