Trial reportProceedings of the National Academy of Sciences of the United States of America2013
Induction of human cardiomyocyte-like cells from fibroblasts by defined factors.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers, 1 of them a synthesis 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
192 citing papers in PubMed, 1 synthesis or guideline pooled it, 327 citations in OpenAlex.
- Cardiac Regeneration: New Insights Into the Frontier of Ischemic Heart Failure Therapy.Frontiers in bioengineering and biotechnology · 2020Pooled it
- Spatial expression of myocardin protein in normal and disease states.American journal of physiology. Cell physiology · 2026Article
- Biologics for cardiovascular diseases: from bench to bedside.Signal transduction and targeted therapy · 2026Review
- Harnessing Lessons from Gel-Based and Advanced Biomaterial Therapeutics to Enable Direct Cellular Reprogramming.Gels (Basel, Switzerland) · 2026Review
- Redefining cellular reprogramming with advanced genomic technologies.Nature reviews. Genetics · 2026Review
- Heart Regeneration for Clinical Application.Internal medicine (Tokyo, Japan) · 2026Review
- Cardiac repair and regeneration: cell therapy, in vivo reprogramming, and the promise of extracellular vesicles.Experimental & molecular medicine · 2025Review
- Advances in fibroblast-based cardiac reprogramming in the treatment of heart disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Reprogramming of human urine cells into cardiomyocytes via a small molecule cocktail in xeno-free conditions.Communications medicine · 2025Article
- Cell Reprogramming, Transdifferentiation, and Dedifferentiation Approaches for Heart Repair.International journal of molecular sciences · 2025Review
- Age-associated metabolic and epigenetic barriers during direct reprogramming of mouse fibroblasts into induced cardiomyocytes.Aging cell · 2025Article
- Revitalizing the heart: strategies and tools for cardiomyocyte regeneration post-myocardial infarction.NPJ Regenerative medicine · 2025Review
- Review
- Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application.Signal transduction and targeted therapy · 2024Review
- Review
- FGF4 and ascorbic acid enhance the maturation of induced cardiomyocytes by activating JAK2-STAT3 signaling.Experimental & molecular medicine · 2024Article
- Review
- Cholesterol-Bearing Polysaccharide-Based Nanogels for Development of Novel Immunotherapy and Regenerative Medicine.Gels (Basel, Switzerland) · 2024Review
- Versatile extracellular vesicle-mediated information transfer: intercellular synchronization of differentiation and of cellular phenotypes, and future perspectives.Inflammation and regeneration · 2024Review
- Next-generation direct reprogramming.Frontiers in cell and developmental biology · 2024Review
132 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heart disease remains a leading cause of death worldwide. Owing to the limited regenerative capacity of heart tissue, cardiac regenerative therapy has emerged as an attractive approach. Direct reprogramming of human cardiac fibroblasts (HCFs) into cardiomyocytes may hold great potential for this purpose. We reported previously that induced cardiomyocyte-like cells (iCMs) can be directly generated from mouse cardiac fibroblasts in vitro and vivo by transduction of three transcription factors: Gata4, Mef2c, and Tbx5, collectively termed GMT. In the present study, we sought to determine whether human fibroblasts also could be converted to iCMs by defined factors. Our initial finding that GMT was not sufficient for cardiac induction in HCFs prompted us to screen for additional factors to promote cardiac reprogramming by analyzing multiple cardiac-specific gene induction with quantitative RT-PCR. The addition of Mesp1 and Myocd to GMT up-regulated a broader spectrum of cardiac genes in HCFs more efficiently compared with GMT alone. The HCFs and human dermal fibroblasts transduced with GMT, Mesp1, and Myocd (GMTMM) changed the cell morphology from a spindle shape to a rod-like or polygonal shape, expressed multiple cardiac-specific proteins, increased a broad range of cardiac genes and concomitantly suppressed fibroblast genes, and exhibited spontaneous Ca(2+) oscillations. Moreover, the cells matured to exhibit action potentials and contract synchronously in coculture with murine cardiomyocytes. A 5-ethynyl-2'-deoxyuridine assay revealed that the iCMs thus generated do not pass through a mitotic cell state. These findings demonstrate that human fibroblasts can be directly converted to iCMs by defined factors, which may facilitate future applications in regenerative medicine.
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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.