ArticleCirculation research2012
MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes.
Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 409 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
409 citing papers in PubMed, 2 syntheses or guidelines pooled it, 763 citations in OpenAlex.
- A Bibliometric and Visualized Analysis of Cardiac Regeneration Over a 20-Year Period.Frontiers in cardiovascular medicine · 2021Pooled it
- Cardiac Regeneration: New Insights Into the Frontier of Ischemic Heart Failure Therapy.Frontiers in bioengineering and biotechnology · 2020Pooled it
- Integrating delivery systems and microenvironmental cues to accelerate clinical translation of cardiac reprogramming.Materials today. Bio · 2026Review
- Impact ofJournal of cardiovascular development and disease · 2026Review
- Hemoglobin inhibits fibroblast-to-cardiomyocyte reprogramming via TLR2/TLR4-dependent chromatin compaction.Molecular therapy. Nucleic acids · 2026Article
- Harnessing Lessons from Gel-Based and Advanced Biomaterial Therapeutics to Enable Direct Cellular Reprogramming.Gels (Basel, Switzerland) · 2026Review
- Evaluation of an experimental model of senescence SAMR1/SAMP8 for microRNA studies in acute myocardial infarction: role of sex and aging.Journal of physiology and biochemistry · 2026Article
- Histone Modifications in Cardiovascular Disease: Mechanisms and Therapeutic Opportunities.MedComm · 2026Review
- The DNA Demethylase TET1 is a Pivotal Regulator of the miR-124/ISX9-Instructed Conversion of Astrocytes to Induced Neurons.Molecular neurobiology · 2026Article
- Advances in MicroRNA-Based Therapies for Cardiac Repair: Emerging Strategies for Treating Myocardial Infarction.Molecular and cellular biochemistry · 2026Review
- A novel endosome-escaping, macrophage-targeted nanoparticle platform for miR-146a delivery with favorable in vivo biodistribution and biocompatibility.bioRxiv : the preprint server for biology · 2026Article
- Endosome-escaping engineered LNP-miR146a with in vivo biodistribution to mitigate inflammation and foreign body giant cell formation.bioRxiv : the preprint server for biology · 2026Article
- Activation of developmental transcription factors using RNA technology promotes heart repair.bioRxiv : the preprint server for biology · 2026Article
- Targeting Cardiac Fibroblast Plasticity for Antifibrotic and Regenerative Therapy in Heart Failure.Cells · 2026Review
- MiRNA Regulations in Cardiotoxicity Induced by Oncologic Therapies and Possible Immune Response.Current medicinal chemistry · 2026Review
- MicroRNA, MicroRNA-lncRNA and MicroRNA-Circular RNA axes, and exosomal MicroRNAs: driving exercise-induced cardioprotection in heart failure.Frontiers in cell and developmental biology · 2026Review
- Refining fibroblast-to-cardiomyocyte transdifferentiation protocols to explore emergent self-organization in cardiac cultures.PloS one · 2026Article
- ECM proteins regulate microRNA-mediated direct reprogramming of fibroblasts into cardiomyocytes via YAP signaling.Frontiers in bioengineering and biotechnology · 2026Article
- Heart Regeneration for Clinical Application.Internal medicine (Tokyo, Japan) · 2026Review
- Integrating synthetic biology to understand and engineer the heart, lung, blood, and sleep systems.Cell systems · 2025Review
349 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
rationaleRepopulation of the injured heart with new, functional cardiomyocytes remains a daunting challenge for cardiac regenerative medicine. An ideal therapeutic approach would involve an effective method at achieving direct conversion of injured areas to functional tissue in situ.
objectiveThe aim of this study was to develop a strategy that identified and evaluated the potential of specific micro (mi)RNAs capable of inducing reprogramming of cardiac fibroblasts directly to cardiomyocytes in vitro and in vivo. METHODS AND
resultsUsing a combinatorial strategy, we identified a combination of miRNAs 1, 133, 208, and 499 capable of inducing direct cellular reprogramming of fibroblasts to cardiomyocyte-like cells in vitro. Detailed studies of the reprogrammed cells demonstrated that a single transient transfection of the miRNAs can direct a switch in cell fate as documented by expression of mature cardiomyocyte markers, sarcomeric organization, and exhibition of spontaneous calcium flux characteristic of a cardiomyocyte-like phenotype. Interestingly, we also found that miRNA-mediated reprogramming was enhanced 10-fold on JAK inhibitor I treatment. Importantly, administration of miRNAs into ischemic mouse myocardium resulted in evidence of direct conversion of cardiac fibroblasts to cardiomyocytes in situ. Genetic tracing analysis using Fsp1Cre-traced fibroblasts from both cardiac and noncardiac cell sources strongly suggests that induced cells are most likely of fibroblastic origin.
conclusionsThe findings from this study provide proof-of-concept that miRNAs have the capability of directly converting fibroblasts to a cardiomyocyte-like phenotype in vitro. Also of significance is that this is the first report of direct cardiac reprogramming in vivo. Our approach may have broad and important implications for therapeutic tissue regeneration in general.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.