ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Direct reprogramming induces vascular regeneration post muscle ischemic injury.
Open access · bronzeAbstract read
In one paragraph
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
5.4field-weighted citation impact, top 3% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
34 citing papers in PubMed, 39 citations in OpenAlex.
- Human induced pluripotent stem cell-derived cardiomyocyte patch enhances cardiac regeneration in a J2N-k hamster model of dilated cardiomyopathy.Regenerative therapy · 2026Article
- Integrating delivery systems and microenvironmental cues to accelerate clinical translation of cardiac reprogramming.Materials today. Bio · 2026Review
- Effects of taurine on skeletal muscle in senescence-accelerated mice and C2C12 myoblasts and myotubes.Amino acids · 2026Article
- Nanomicelle-Based Multi-mRNA Delivery Promotes Cardiac Repair After Myocardial Infarction.Small science · 2026Article
- "More" Artificial mRNAs: Beyond the Art of Nature.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Messenger RNA therapy in bone and joint diseases: Rationale, delivery systems, and applications.Biomaterials translational · 2026Article
- Transient overexpression of hPKM2 in porcine cardiomyocytes prevents heart failure after myocardial infarction.Nature communications · 2025Article
- Using modified mRNA for cardiomyocyte proliferation and cardiac genetic disease modelling and treatment.Biochemical Society transactions · 2025Review
- In Vivo Targeted Reprogramming of Cardiac Fibroblasts for Heart Regeneration: Advances and Therapeutic Potential.Bioengineering (Basel, Switzerland) · 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
- Review
- Cardiac Fibroblasts: Helping or Hurting.Genes · 2025Review
- Direct fibroblast reprogramming: an emerging strategy for treating organic fibrosis.Journal of translational medicine · 2025Review
- Control of cell fate upon transcription factor-driven cardiac reprogramming.Current opinion in genetics & development · 2024Review
- Modifying miRs for effective reprogramming of fibroblasts to cardiomyocytes.Molecular therapy. Nucleic acids · 2024Article
- Bioengineering Cell Therapy for Treatment of Peripheral Artery Disease.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Fibroblast Reprogramming in Cardiac Repair.JACC. Basic to translational science · 2024Review
- Radiation-induced multi-organ injury.International journal of radiation biology · 2024Article
- Next-generation direct reprogramming.Frontiers in cell and developmental biology · 2024Review
- Cell Reprogramming and Differentiation Utilizing Messenger RNA for Regenerative Medicine.Journal of developmental biology · 2023Review
Corrections and comments
- Commented on by
Authors and funding
24 authors at 4 institutions in 2 countries.
Keerat KaurCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Yoav HadasCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Ann Anu KurianCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Magdalena M ŻakCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Jimeen YooCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Asharee MahmoodCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Hanna GirardCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Rinat KomargodskiCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Toshiro IoResearch Department, Ono Pharmaceutical Co. Ltd., Osaka 103-0023, Japan.
Maria Paola SantiniCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Nishat SultanaCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Mohammad Tofael Kabir SharkarCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Ajit MagadumCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Anthony FargnoliCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Seonghun YoonCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Elena ChepurkoCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Vadim ChepurkoCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Efrat EliyahuDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Multiscale Biology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Dalila PintoDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Djamel LebecheCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Jason C KovacicCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Roger J HajjarPhospholamban Foundation, Amsterdam 1775 ZH, the Netherlands.
Shahin RafiiDivision of Regenerative Medicine, Ansary Stem Cell Institute, Weill Cornell Medicine, New York, NY 10065, USA.
Lior ZangiCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: lior.zangi@mssm.edu.
Icahn School of Medicine at Mount Sinai · USAllen Institute for Brain Science · USCornell University · USOno Pharmaceutical (Japan) · JP
Funding
TRAINING PROGRAM IN MOLECULAR AND CELLULAR CARDIOLOGYT32HL007824 · NHLBI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI GELB, BRUCE D · 1995 to 2022
$8.6MInduction of Cardiomyocyte Proliferation via Transient Expression of Cell Cycle Factors as a Promising Therapy for Heart FailureR01HL147921 · NHLBI · UNIVERSITY OF LOUISVILLE · PI Tamer M A Mohamed, Jonathan Satin · 2020 to 2026
$5.3MMapping the role of long noncoding RNAs in gene regulatory networks in schizophreniaR01MH109715 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI PINTO, DALILA · 2018 to 2022
$4.0MDeciphering the Neonatal Cardiac Regenerative Potential and Regulators in Large AnimalsR01HL149137 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SADEK, HESHAM, ZANGI, LIOR · 2019 to 2022
$2.5MCardiomyocyte-specific modified mRNA of Pkm2 for induction of cardiac regeneration in ischemic heart failureR01HL142768 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ZANGI, LIOR · 2018 to 2022
$2.1MLong non-coding RNAs in gene regulatory networks underlying AutismR21MH105881 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI PINTO, DALILA · 2015 to 2016
$465kNHLBI NIH HHS R01 HL142768NHLBI NIH HHS R01 HL147921NHLBI NIH HHS R01 HL149137NHLBI NIH HHS T32 HL007824NIMH NIH HHS R01 MH109715NIMH NIH HHS R21 MH105881
Abstract
Reprogramming non-cardiomyocytes (non-CMs) into cardiomyocyte (CM)-like cells is a promising strategy for cardiac regeneration in conditions such as ischemic heart disease. Here, we used a modified mRNA (modRNA) gene delivery platform to deliver a cocktail, termed 7G-modRNA, of four cardiac-reprogramming genes-Gata4 (G), Mef2c (M), Tbx5 (T), and Hand2 (H)-together with three reprogramming-helper genes-dominant-negative (DN)-TGFβ, DN-Wnt8a, and acid ceramidase (AC)-to induce CM-like cells. We showed that 7G-modRNA reprogrammed 57% of CM-like cells in vitro. Through a lineage-tracing model, we determined that delivering the 7G-modRNA cocktail at the time of myocardial infarction reprogrammed ∼25% of CM-like cells in the scar area and significantly improved cardiac function, scar size, long-term survival, and capillary density. Mechanistically, we determined that while 7G-modRNA cannot create de novo beating CMs in vitro or in vivo, it can significantly upregulate pro-angiogenic mesenchymal stromal cells markers and transcription factors. We also demonstrated that our 7G-modRNA cocktail leads to neovascularization in ischemic-limb injury, indicating CM-like cells importance in other organs besides the heart. modRNA is currently being used around the globe for vaccination against COVID-19, and this study proves this is a safe, highly efficient gene delivery approach with therapeutic potential to treat ischemic diseases.
Indexed as
AnimalsAnimals, NewbornCells, CulturedCellular ReprogrammingDisease Models, AnimalFemaleFibroblastsGenetic TherapyHumansIschemiaMaleMiceMice, Knockout, ApoEMuscle, SkeletalMyocardial InfarctionMyocytes, CardiacRNA, Messengercardiac repaircardiac reprogrammingcardiovascular reprogramminggene therapyhindlimb ischemiamodified mRNA
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390
Registered trials
None linked
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.