Work

Impact of IL-6 and TGF-β1 on equine mesenchymal stromal cell homing gene expression

Year: 2025

Type: article

Abstract: Mesenchymal stromal cells (MSCs) support wound healing through immunomodulation and by promoting tissue organization. Cell tracking studies demonstrate that MSCs must ‘home’ to injuries in order to participate in reparative processes. It has been reported that in vivo cell tracking labels, including superparamagnetic iron oxide particles (SPIOs), can alter MSC homing. Homing is thought to occur in coordinated steps including tethering, activation, arrest, diapedesis, and migration, guided by chemotactic stimuli. Equine distal limb injuries, which are commonly treated with MSCs, possess a distinct cytokine profile that could promote MSC homing. Acutely, distal limb injuries produce high levels of interleukin-6 (IL-6) followed by elevated transforming growth factor β1 (TGF-β1) in later healing stages. It remains unclear whether these cytokines modulate homing-associated gene expression in equine MSCs. This study used RT-qPCR to evaluate homing-related gene expression in unlabeled or SPIO-labeled equine bone-marrow derived MSCs (eBM-MSCs) exposed to IL-6 [300 ng/mL], TGF-β1 [6 ng/mL], or both, for 12- or 24-h. We created a panel of 18 genes representing each stage of the homing cascade. Data were analyzed using a linear mixed model. Results showed a significant interaction between SPIO labeling and gene expression for CD106, with SPIO-labeled cells expressing higher levels of CD106 than unlabeled cells. Additionally, cytokine exposure but not time significantly affected gene expression: TGF-β1 alone enhanced expression of genes involved in integrin-mediated tethering and arrest, while co-exposure with IL-6 downregulated these same genes. In conclusion, eBM-MSCs homing in vivo may be impaired by acute inflammation exhibiting high levels of IL-6 and TGF-β1. • Mesenchymal stem cells respond to inflammatory signals to ‘home’ to sites of injury. • Stimulating MSCs with both IL-6 and TGF-β1 downregulated tethering and arrest genes. • IL-6 stimulation supported IL6Rβ expression but downregulated MMP-9 expression. • TGF-β1 exposure promoted activation and integrin mediated arrest associated genes. • Administering MSCs during acute phases of inflammation may not support MSC homing.

Source: Research in Veterinary Science

DOI: 10.1016/j.rvsc.2025.105969