Modulating Lineage Specification in Stem Cell Differentiation via Bioelectrical Stimulation Intensity Matching

Abstract Development and regeneration in biological tissues are fundamentally affected by stem‐cell‐fate commitment. Bioelectricity is heterogeneous between different tissues and crucially regulates cell behaviors, including cell differentiation. However, the effects of heterogeneous bioelectricity on stem‐cell differentiation remain poorly understood. Herein, it is shown that providing stem cells with electrical stimulation matching the endogenous membrane potentials of cells derived from different tissues (osteogenic‐related: −55.05 ± 4.22 mV, neurogenic‐related: −84.8 ± 7.48 mV) can induce their osteogenic or neurogenic lineage commitment. Molecular dynamics simulations indicated that the osteogenic‐related surface potential favors the adsorption of fibronectin, while the neurogenic‐related surface potential enhances the adsorption of FGF‐2. These different protein adsorptions trigger either downstream Wnt or Erk signaling, which direct stem‐cell differentiation. Surface‐potential‐mediated lineage‐specification of stem cells using bioelectrical intensity has enormous potential application value in tissue regenerative therapy.