Low-dose lipopolysaccharide pretreatment enhanced the proliferation and antibacterial activity of human adipose-derived mesenchymal stem cells.

INTRODUCTION: Adipose-derived mesenchymal stem cells (ADSCs) have been widely investigated for their pro-angiogenic and immunomodulatory roles in the repair of infected wounds. However, the direct antimicrobial effects of ADSCs and the underlying regulatory mechanisms remain poorly characterized. In particular, the functional modulation of ADSCs by low-dose lipopolysaccharide (LPS) preconditioning has not been systematically investigated. METHODS: We evaluated the effects of LPS preconditioning on the proliferation and apoptosis of human ADSCs (hADSCs), as well as the antimicrobial activity and wound-healing potential of hADSC-conditioned medium (hADSC-CM). RESULTS: Analysis demonstrated that at concentrations ranging from 10 to 500 ng/mL, LPS significantly enhanced the proliferation of hADSCs, with the highest viability observed at 500 ng/mL and no evidence of increased apoptosis. Moreover, LPS preconditioning markedly upregulated the expression of antimicrobial peptides (LL-37 and HBD-2) in hADSC-CM, leading to improved inhibition ofandgrowth. In vivo experiments further confirmed that 500 ng/mL of LPS-hADSC-CM significantly accelerated the healing of infected wounds, increased collagen deposition, and downregulated the expression of iNOS, thus suggesting enhanced inflammation resolution and tissue regeneration. CONCLUSION: These findings highlight the capacity of LPS preconditioning to potentiate the biological functions of hADSCs, enhancing the antimicrobial and regenerative efficacy of hADSC-CM, and providing a promising strategy for the treatment of chronically infected wounds.