ArticleStem cell research & therapy2021
Pluripotent stem cell-induced skeletal muscle progenitor cells with givinostat promote myoangiogenesis and restore dystrophin in injured Duchenne dystrophic muscle.
Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Impact of dystrophin deficiency on vascular smooth muscle cell.Scientific reports · 2025Article
- Combined Endurance and Resistance Exercise Mitigates Age-Associated Cardiac Dysfunction.Advanced biology · 2025Article
- Advancements in skeletal muscle tissue engineering: strategies for repair and regeneration of skeletal muscle beyond self-repair.Regenerative biomaterials · 2025Review
- Stem/progenitor cell-based therapy for Duchenne muscular dystrophy.Frontiers in cell and developmental biology · 2025Review
- The paradoxical role of stem cells in osteosarcoma: from pathogenesis to therapeutic breakthroughs.Frontiers in oncology · 2025Review
- Engineering large-scale hiPSC-derived vessel-integrated muscle-like lattices for enhanced volumetric muscle regeneration.Trends in biotechnology · 2024Article
- Induced Pluripotent Stem Cells for Tissue-Engineered Skeletal Muscles.International journal of molecular sciences · 2023Review
- Article
- Early Differentiation Signatures in Human Induced Pluripotent Stem Cells Determined by Non-Targeted Metabolomics Analysis.Metabolites · 2023Article
- Histone Deacetylases: Molecular Mechanisms and Therapeutic Implications for Muscular Dystrophies.International journal of molecular sciences · 2023Review
- Re-examination of therapeutic management of muscular dystrophies using a vascular smooth muscle-centered approach.Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2023Article
- Skeletal Muscle Regeneration in Cardiotoxin-Induced Muscle Injury Models.International journal of molecular sciences · 2022Review
- Therapeutic Application of Extracellular Vesicles-Capsulated Adeno-Associated Virus Vector viaInternational journal of molecular sciences · 2022Review
- Hypoxic Conditions Promote the Angiogenic Potential of Human Induced Pluripotent Stem Cell-Derived Extracellular Vesicles.International journal of molecular sciences · 2021Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDuchenne muscular dystrophy (DMD) is caused by mutations of the gene that encodes the protein dystrophin. A loss of dystrophin leads to severe and progressive muscle wasting in both skeletal and heart muscles. Human induced pluripotent stem cells (hiPSCs) and their derivatives offer important opportunities to treat a number of diseases. Here, we investigated whether givinostat (Givi), a histone deacetylase inhibitor, with muscle differentiation properties could reprogram hiPSCs into muscle progenitor cells (MPC) for DMD treatment.
methodsMPC were generated from hiPSCs by treatment with CHIR99021 and givinostat called Givi-MPC or with CHIR99021 and fibroblast growth factor as control-MPC. The proliferation and migration capacity were investigated by CCK-8, colony, and migration assays. Engraftment, pathological changes, and restoration of dystrophin were evaluated by in vivo transplantation of MPC. Conditioned medium from cultured MPC was collected and analyzed for extracellular vesicles (EVs).
resultsGivi-MPC exhibited superior proliferation and migration capacity compared to control-MPC. Givi-MPC produced less reactive oxygen species (ROS) after oxidative stress and insignificant expression of IL6 after TNF-α stimulation. Upon transplantation in cardiotoxin (CTX)-injured hind limb of Mdx/SCID mice, the Givi-MPC showed robust engraftment and restored dystrophin in the treated muscle than in those treated with control-MPC or human myoblasts. Givi-MPC significantly limited infiltration of inflammatory cells and reduced muscle necrosis and fibrosis. Additionally, Givi-MPC seeded the stem cell pool in the treated muscle. Moreover, EVs released from Givi-MPC were enriched in several miRNAs related to myoangiogenesis including miR-181a, miR-17, miR-210 and miR-107, and miR-19b compared with EVs from human myoblasts.
conclusionsIt is concluded that hiPSCs reprogrammed into MPC by givinostat possessing anti-oxidative, anti-inflammatory, and muscle gene-promoting properties effectively repaired injured muscle and restored dystrophin in the injured muscle.
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