Effects of Hypoxia and Lipopolysaccharide on the Migration Capacity and Paracrine Factor Expression of Human Umbilical Cord Mesenchymal Stem Cells

Abstract

Background: Mesenchymal stem cells (MSCs) have emerged as a promising strategy for tissue regeneration. Although hypoxia or lipopolysaccharide (LPS) has been shown to affect the regenerative capacity of MSCs, their combined effects on MSCs are still unknown. We examined the effects of hypoxia and LPS on MSC migration rates and paracrine expression. Materials and Methods: Umbilical cord-derived MSCs (UC-MSCs) were isolated and characterized. Wound scratch assays assessed migration and proliferation under hypoxic conditions, LPS supplementation, or both. The expression of paracrine factors was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Results: Twenty-four hours post-scratching, the gap closure in UC-MSCs after both hypoxia exposure and LPS treatment was significantly enhanced than those in the control group (p=0.008) or those subjected to individual treatments (p=0.028 vs. hypoxia and p=0.0021 vs. LPS). Serum-supplemented media further maximized these synergistic effects. Combined hypoxia and LPS did not affect vascular endothelial growth factor (VEGF) mRNA levels. In contrast, both hypoxia exposure and LPS treatment decreased the transcript levels of hepatocyte growth factor (HGF), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β). Conclusion: These findings indicate that the combination of hypoxia and LPS treatment affects the proliferative capacity of UC-MSCs, thus enhancing the MSC migration rate. However, hypoxia and LPS together reduce the expression of paracrine factors in UC-MSCs, potentially attenuating the immunomodulatory efficacy of UC-MSCs in tissue injury microenvironments.