ArticleScience advances2025
Extracellular fluid viscosity regulates human mesenchymal stem cell lineage and function.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed.
- Mechanically preconditioned stem cells therapy using bioinspired liver-mimetic microspheres for functional liver repair.Bioactive materials · 2026Article
- In situ processing of fibrous hydrogels by photochemistry for adaptive cellular microenvironments.Science advances · 2026Article
- Review
- Hydrogels: current biomedical applications and future directions.Molecular biomedicine · 2026Review
- Beyond Potency: Emerging Determinants and Optimization Strategies Enhancing Therapeutic Efficacy of Adult Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Advancing mechanobiology from single molecules to complex cellular systems.Nature nanotechnology · 2026Review
- Open micro-valley chip reveals long-term viscosity-induced glioblastoma cellular invasion states.Microsystems & nanoengineering · 2026Article
- Macrophage-derived legumain ameliorates excessive mechanical stress-induced ferroptosis of nucleus pulposus cells and intervertebral disc degeneration via integrin αvβ3-Hippo signaling.Cellular & molecular biology letters · 2026Article
- Article
- Fungal commensal promotes intestinal repair via its secreted peptide in mice.Nature microbiology · 2026Article
- Mechanical regulation of metabolism, epigenetics, and their interplay.npj biomedical innovations · 2026Review
- Acute priming using elevated fluid viscosity recovers 'bioRxiv : the preprint server for biology · 2026Article
- Extracellular matrix stiffness conditions glioblastoma cells for long-term migration: Mechanical memory as a driver of invasion and recurrence in glioblastoma.Neuro-oncology · 2026Review
- Fibrinogen in extracellular matrix remodeling: functional switching, source heterogeneity, and biomaterial translation.Frontiers in cell and developmental biology · 2026Review
- NHE1 in macrophages promotes octanal/Olfr2-induced atherosclerosis via calcium-dependent ROS and NLRP3 inflammasome activation.Scientific reports · 2025Article
- Mechanosensitive ion channels and inflammation: key links in cellular signal transduction.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Navigating confinement: Mechanotransduction and metabolic adaptation.Current opinion in cell biology · 2025Review
- Crosslinking stabilization strategy: A novel approach to cartilage-like repair of annulus fibrosus (AF) defects.Materials today. Bio · 2025Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Human mesenchymal stem cells (hMSCs) respond to mechanical stimuli, including stiffness and viscoelasticity. To date, it is unknown how extracellular fluid viscosity affects hMSC function on substrates of different stiffness and viscoelasticity. While hMSCs assume an adipogenic phenotype on gels of low stiffness and prescribed stress relaxation times, elevated fluid viscosity is sufficient to bias hMSCs toward an osteogenic phenotype. Elevated viscosity induces Arp2/3-dependent actin remodeling, enhances NHE1 activity, and promotes hMSC spreading via up-regulation of integrin-linked kinase. The resulting increase in membrane tension triggers the activation of transient receptor potential cation vanilloid 4 to facilitate calcium influx, thereby stimulating RhoA/ROCK and driving YAP-dependent RUNX2 translocation to the nucleus, leading to osteogenic differentiation. hMSCs on soft gels at elevated relative to basal viscosity favor an M2 macrophage phenotype. This study establishes fluid viscosity as a key physical cue that imprints osteogenic memory in hMSCs and promotes an immunosuppressive phenotype.
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Registered trials
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