ArticleSkeletal muscle2024
Motor neurons and endothelial cells additively promote development and fusion of human iPSC-derived skeletal myocytes.
Article in Skeletal muscle, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Manufacturing, Cell Regulation, and Coculture Strategies for Vascularization and Neural Innervation of Skeletal Muscle Tissue.Advanced healthcare materials · 2026Review
- Modular Tissue-Engineered Motor Units Featuring Spinal Motor Neurons Innervating Self-Assembled Myofiber Bundles.Macromolecular bioscience · 2026Article
- Re-innervation of neuromuscular junctions by a conductive polypyrrole/silk fibroin/GelMA hydrogel facilitated functional skeletal muscle regeneration following volumetric muscle loss.Journal of orthopaedic translation · 2026Article
- Skeletal muscle reprogramming in peripheral nerve injury: mechanisms, therapeutic roles, and complication management.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- Sprayable hydrogel sponge for neurovascular microenvironment reconstruction and inflammation modulation in diabetic wound healing.Bioactive materials · 2025Article
- Geometrically-engineered human motor assembloids-on-a-chip for neuromuscular interaction readout and hypoxia-driven disease modeling.Nature communications · 2025Article
- Screening of hub genes and immunocytes related to tendon injury based on bioinformatics and machine learning models.Scientific reports · 2025Article
- Tensile Forces and Nanofiber Alignment Influence Both Innervated and Non-Innervated Skeletal Myofiber Formation in Custom Mechanobioreactors.Biotechnology journal · 2025Article
- Single-Cell RNA-Seq Reveals the Pseudo-temporal Dynamic Evolution Characteristics of ADSCs to Neuronal Differentiation.Cellular and molecular neurobiology · 2024Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundNeurovascular cells have wide-ranging implications on skeletal muscle biology regulating myogenesis, maturation, and regeneration. Although several in vitro studies have investigated how motor neurons and endothelial cells interact with skeletal myocytes independently, there is limited knowledge about the combined effect of neural and vascular cells on muscle maturation and development.
methodsHere, we report a triculture system comprising human-induced pluripotent stem cell (iPSC)-derived skeletal myocytes, human iPSC-derived motor neurons, and primary human endothelial cells maintained under controlled media conditions. Briefly, iPSCs were differentiated to generate skeletal muscle progenitor cells (SMPCs). These SMPCs were seeded at a density of 5 × 10
resultsWe observed that motor neurons independently promoted myofiber fusion, upregulated neuromuscular junction genes, and maintained a molecular niche supportive of muscle maturation. Endothelial cells independently did not support myofiber fusion and downregulated expression of LRP4 but did promote expression of type II specific myosin isoforms. However, neurovascular cells in combination exhibited additive increases in myofiber fusion and length, enhanced production of Agrin, along with upregulation of several key genes like MUSK, RAPSYN, DOK-7, and SLC2A4. Interestingly, more divergent effects were observed in expression of genes like MYH8, MYH1, MYH2, MYH4, and LRP4 and secretion of key molecular factors like amphiregulin and IGFBP-4.
conclusionsNeurovascular cells when cultured in combination with skeletal myocytes promoted myocyte fusion with concomitant increase in expression of various neuromuscular genes. This triculture system may be used to gain a deeper understanding of the effects of the neurovascular niche on skeletal muscle biology and pathophysiology.
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