Mechanically preconditioned stem cells therapy using bioinspired liver-mimetic microspheres for functional liver repair.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Hepatocyte-like cells (HLCs) represent a promising therapeutic approach for acute liver failure (ALF), offering an alternative to primary hepatocytes, which are in short supply. Given the viscoelastic tissue properties of the liver and the growing recognition of the mechanical cues in physiology and disease, we investigated how ALF-induced changes in the liver's mechanical microenvironment might affect HLC-based cell therapy. Here, driven by specific disease-derived mechanical cues, we designed bioinspired hydrogel microspheres with tunable liver viscoelasticity to mimic the mechanical niche of healthy versus ALF liver tissue. We show that a fast-relaxation hydrogel niche mimicking the healthy liver guides the efficient differentiation of human adipose-derived mesenchymal stem cells (hADSCs) into functional HLCs by suppressing the formation of abnormal stress fibers and pathological YAP nuclear translocation through the ROCK axis. In both the carbon tetrachloride-induced and partial hepatectomy-induced ALF mouse models, these mechanically preconditioned HLCs exhibit significant therapeutic efficacy, promoting robust liver regeneration and acting as active mechanical regulators to suppress aberrant host mechanotransduction and remodel the diseased microenvironment. This disease mechanobiology-oriented strategy provides insights into the design of viscoelastic biomaterials for re

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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