ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
CRISPR activation of endogenous genes reprograms fibroblasts into cardiovascular progenitor cells for myocardial infarction therapy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Pooled it
- Biomaterial-Assisted Stem Cell Therapy and Exosome Delivery in Myocardial Infarction: A Narrative Review.Biomimetics (Basel, Switzerland) · 2026Review
- Review
- Biologics for cardiovascular diseases: from bench to bedside.Signal transduction and targeted therapy · 2026Review
- Clinical translation of epigenome editing technologies.Current opinion in biomedical engineering · 2026Article
- Histone Modifications in Cardiovascular Disease: Mechanisms and Therapeutic Opportunities.MedComm · 2026Review
- Targeting Cardiac Fibroblast Plasticity for Antifibrotic and Regenerative Therapy in Heart Failure.Cells · 2026Review
- Article
- Cell and tissue reprogramming: Unlocking a new era in medical drug discovery.Pharmacological reviews · 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
- Cellular Models of Aging and Senescence.Cells · 2025Review
- Harnessing extracellular vesicles to deliver genetic medicine for cardiac repair.Nanomedicine (London, England) · 2025Article
- Unraveling the Complex Cellular Repair Mechanisms Following Myocardial Infarction.International journal of molecular sciences · 2025Review
- Leveraging cardiac reprogramming with CRISPRa-SAM technology.Molecular therapy. Nucleic acids · 2025Article
- An overview on cardiac regeneration revolution: exploring the promise of stem cell therapies.Molecular biology reports · 2025Review
- Cardiac Fibroblasts: Helping or Hurting.Genes · 2025Review
- Cell Reprogramming, Transdifferentiation, and Dedifferentiation Approaches for Heart Repair.International journal of molecular sciences · 2025Review
- The epigenetic regulation of crosstalk between cardiac fibroblasts and other cardiac cell types during stress.Frontiers in cardiovascular medicine · 2025Review
- Nanomedicine for Diagnosis and Treatment of Cardiac Fibrosis.International journal of nanomedicine · 2025Review
- Review
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17 authors at 3 institutions in 1 country.
Funding
Abstract
Fibroblasts can be reprogrammed into cardiovascular progenitor cells (CPCs) using transgenic approaches, although the underlying mechanism remains unclear. We determined whether activation of endogenous genes such as Gata4, Nkx2.5, and Tbx5 can rapidly establish autoregulatory loops and initiate CPC generation in adult extracardiac fibroblasts using a CRISPR activation system. The induced fibroblasts (>80%) showed phenotypic changes as indicated by an Nkx2.5 cardiac enhancer reporter. The progenitor characteristics were confirmed by colony formation and expression of cardiovascular genes. Cardiac sphere induction segregated the early and late reprogrammed cells that can generate functional cardiomyocytes and vascular cells in vitro. Therefore, they were termed CRISPR-induced CPCs (ciCPCs). Transcriptomic analysis showed that cell cycle and heart development pathways were important to accelerate CPC formation during the early reprogramming stage. The CRISPR system opened the silenced chromatin locus, thereby allowing transcriptional factors to access their own promoters and eventually forming a positive feedback loop. The regenerative potential of ciCPCs was assessed after implantation in mouse myocardial infarction models. The engrafted ciCPCs differentiated into cardiovascular cells in vivo but also significantly improved contractile function and scar formation. In conclusion, multiplex gene activation was sufficient to drive CPC reprogramming, providing a new cell source for regenerative therapeutics.
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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.