ArticleSignal transduction and targeted therapy2022
Excessive branched-chain amino acid accumulation restricts mesenchymal stem cell-based therapy efficacy in myocardial infarction.
Article in Signal transduction and targeted therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 49 citations in OpenAlex.
- Exercise suppresses IP6K3 to modulate BCAA metabolism and ferroptosis in MASLD.Cellular & molecular biology letters · 2026Article
- Interplay between ischemia-reperfusion and metabolic reprogramming.Apoptosis : an international journal on programmed cell death · 2026Review
- Defective branched-chain amino acid catabolism promotes pulmonary fibrosis by inducing apoptosis resistance of myofibroblasts in mice.Cell communication and signaling : CCS · 2026Article
- Dietary intake and BCAA metabolism regulate pulmonary fibrosis through KDM4A-mediated epigenetic remodeling in male mice.Nature communications · 2026Article
- DUX4-induced HSATII RNA accumulation drives protein aggregation, impacting RNA processing pathways.The Journal of cell biology · 2026Article
- Multimodal Therapeutic Strategies Targeting BCAA Metabolism in Diabetic Cardiomyopathy: A Path to Cardioprotection.Cardiovascular toxicology · 2025Review
- HIF-1α modulates β-catenin pathway to enhance the survival and angiogenesis of PBMSCs under hypoxia environment.World journal of stem cells · 2025Article
- Kynurenine-mediated redox regulation provides neuroprotection in central retinal artery occlusion.Journal of translational medicine · 2025Article
- Mesenchymal Stem Cell-Mediated Targeted Drug Delivery Systems for Hepatocellular Carcinoma: Current Advances and Future Directions.Bioengineering (Basel, Switzerland) · 2025Review
- Article
- Metabolic regulation for the treatment of ischemic heart disease with stem cells and extracellular vesicles.NPJ cardiovascular health · 2025Review
- Immunoinflammation and post-translational modifications in the aging process.Journal of translational medicine · 2025Review
- Dietary branched-chain amino acids intake and coronary artery calcium progression: insights from the coronary artery risk development in young adults (CARDIA) study.European journal of nutrition · 2025Observational
- Article
- BCAA metabolism in cancer progression and therapy resistance: The balance between fuel and cell signaling.Frontiers in pharmacology · 2025Review
- Escin Preincubation Enhances the Therapeutic Effect of Umbilical Cord-Derived Mesenchymal Stem Cells in a Rat Model of Myocardial Infarction.Stem cells international · 2025Article
- Mesenchymal Stem Cells and Their Extracellular Vesicles Are a Promising Alternative to Antibiotics for Treating Sepsis.Bioengineering (Basel, Switzerland) · 2024Review
- Pretreatment with Notoginsenoside R1 enhances the efficacy of neonatal rat mesenchymal stem cell transplantation in model of myocardial infarction through regulating PI3K/Akt/FoxO1 signaling pathways.Stem cell research & therapy · 2024Article
- Pretreatment with growth differentiation factor 15 augments cardioprotection by mesenchymal stem cells in myocardial infarction by improving their survival.Stem cell research & therapy · 2024Article
- Therapeutic Applications of Engineered Mesenchymal Stromal Cells for Enhanced Angiogenesis in Cardiac and Cerebral Ischemia.Stem cell reviews and reports · 2024Review
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesenchymal stem cells (MSCs) delivered into the post-ischemic heart milieu have a low survival and retention rate, thus restricting the cardioreparative efficacy of MSC-based therapy. Chronic ischemia results in metabolic reprogramming in the heart, but little is known about how these metabolic changes influence implanted MSCs. Here, we found that excessive branched-chain amino acid (BCAA) accumulation, a metabolic signature seen in the post-ischemic heart, was disadvantageous to the retention and cardioprotection of intramyocardially injected MSCs. Discovery-driven experiments revealed that BCAA at pathological levels sensitized MSCs to stress-induced cell death and premature senescence via accelerating the loss of histone 3 lysine 9 trimethylation (H3K9me3). A novel mTORC1/DUX4/KDM4E axis was identified as the cause of BCAA-induced H3K9me3 loss and adverse phenotype acquisition. Enhancing BCAA catabolic capability in MSCs via genetic/pharmacological approaches greatly improved their adaptation to the high BCAA milieu and strengthened their cardioprotective efficacy. We conclude that aberrant BCAA accumulation is detrimental to implanted MSCs via a previously unknown metabolite-signaling-epigenetic mechanism, emphasizing that the metabolic changes of the post-ischemic heart crucially influence the fate of implanted MSCs and their therapeutic benefits.
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