<p>Surgical site infection increases the risk of morbidity and mortality in patients; among them, aortic graft infections present a poor prognosis. Previous clinical studies have demonstrated the efficacy of omentum flaps, a type of adipose tissue containing mesenchymal stem cells, in inhibiting SSI development in cardiothoracic surgery. However, how omental tissues prevent bacterial infection is still under investigation. Although mesenchymal stem cell is a type of cells that are reported to possess the ability to control infection, most studies have used mesenchymal stem cells derived from bone marrow or subcutaneous adipose tissues and the antibacterial properties of those derived from omentum (oAT-MSC) are still obscured. In the present study, we found that conditioned media (CM) derived from oAT-MSC possessed the ability to impair the growth of <i>S. aureus</i> and MRSA strains, similar to those derived from mesenchymal stem cells of subcutaneous adipose tissue. In addition, concentrated CM from oAT-MSC protected endothelial cells, preserving their morphology and functionality and reducing intracellular ROS following bacterial exposure. Furthermore, in a mouse infection model with <i>S. aureus</i>, concentrated CM from oAT-MSC supported mouse survival and facilitated post-infection wound healing by promoting re-epithelialization and vascularization. A transcriptomic profile analysis of oAT-MSC revealed the high expression of <i>serpine</i>1, encoding for PAI-1 as a secreted agent involved in protecting endothelial functions under <i>S. aureus</i> infection. Our findings suggest a role for oAT-MSC in the efficacy of omentum grafts in cardiothoracic surgery to prevent <i>S. aureus</i>. Additionally, with the ability to prevent infections and preserve the endothelial function under pathological conditions, oAT-MSC-derived secretome could potentially be an effective cell-free tool for <i>S. aureus</i> infection control and improvement of clinical outcomes in surgeries.</p>

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Omentum-Derived Mesenchymal Stem Cells Promote Antibacterial Effects and Protect Endothelial Functions via PAI-1

  • Adeline Castro Ramos,
  • Cat-Khanh Vuong,
  • Mizuho Fukushige,
  • Yuri Ushijima,
  • Kazuya Morikawa,
  • Motoo Osaka,
  • Chiho Tokunaga,
  • Yuji Hiramatsu,
  • Osamu Ohneda

摘要

Surgical site infection increases the risk of morbidity and mortality in patients; among them, aortic graft infections present a poor prognosis. Previous clinical studies have demonstrated the efficacy of omentum flaps, a type of adipose tissue containing mesenchymal stem cells, in inhibiting SSI development in cardiothoracic surgery. However, how omental tissues prevent bacterial infection is still under investigation. Although mesenchymal stem cell is a type of cells that are reported to possess the ability to control infection, most studies have used mesenchymal stem cells derived from bone marrow or subcutaneous adipose tissues and the antibacterial properties of those derived from omentum (oAT-MSC) are still obscured. In the present study, we found that conditioned media (CM) derived from oAT-MSC possessed the ability to impair the growth of S. aureus and MRSA strains, similar to those derived from mesenchymal stem cells of subcutaneous adipose tissue. In addition, concentrated CM from oAT-MSC protected endothelial cells, preserving their morphology and functionality and reducing intracellular ROS following bacterial exposure. Furthermore, in a mouse infection model with S. aureus, concentrated CM from oAT-MSC supported mouse survival and facilitated post-infection wound healing by promoting re-epithelialization and vascularization. A transcriptomic profile analysis of oAT-MSC revealed the high expression of serpine1, encoding for PAI-1 as a secreted agent involved in protecting endothelial functions under S. aureus infection. Our findings suggest a role for oAT-MSC in the efficacy of omentum grafts in cardiothoracic surgery to prevent S. aureus. Additionally, with the ability to prevent infections and preserve the endothelial function under pathological conditions, oAT-MSC-derived secretome could potentially be an effective cell-free tool for S. aureus infection control and improvement of clinical outcomes in surgeries.