Cell Type-Specific Anti-Adhesion Properties of Peritoneal Cell Treatment with Plasma-Activated Media (PAM)

Abstract

Postoperative abdominal adhesions are responsible for serious clinical disorders. Administration of plasma-activated media (PAM) to cell type-specific modulated proliferation and protein biosynthesis is a promising therapeutic strategy to prevent pathological cell responses in the context of wound healing disorders. We analyzed PAM as a therapeutic option based on cell type-specific anti-adhesive responses. Primary human peritoneal fibroblasts and mesothelial cells were isolated, characterized and exposed to different PAM dosages. Cell type-specific PAM effects on different cell components were identified by contact- and marker-independent Raman imaging, followed by thorough validation by specific molecular biological methods. The investigation revealed cell type-specific molecular responses after PAM treatment, including significant cell growth retardation in peritoneal fibroblasts due to transient DNA damage, cell cycle arrest and apoptosis. We identified a therapeutic dose window wherein specifically pro-adhesive peritoneal fibroblasts were targeted, whereas peritoneal mesothelial cells retained their anti-adhesive potential of epithelial wound closure. Finally, we demonstrate that PAM treatment of peritoneal fibroblasts reduced the expression and secretion of pro-adhesive cytokines and extracellular matrix proteins. Altogether, we provide insights into biochemical PAM mechanisms which lead to cell type-specific pro-therapeutic cell responses. This may open the door for the prevention of pro-adhesive clinical disorders.

Conductive Gas Plasma Treatment Augments Tumor Toxicity of Ringer’s Lactate Solutions in a Model of Peritoneal Carcinomatosis

“…In addition to immune cell suppression, desmoplastic reactions of tumor resident stromal fibroblasts can occur, e.g., pancreatic stellate cells (PSC) in the context of pancreatic ductal carcinoma, which are a major cause of therapy resistance and poor patient outcome. Direct and indirect plasma treatment regimens have recently been shown to counteract PSC activation and extracellular matrix remodeling [ 46 , 59 , 60 , 61 ], as well as exuberant proliferation and activity of stromal fibroblasts after peritoneal surgery and prolonged inflammation [ 62 ], which translates to conditions in the TME that might be additionally beneficial after cytoreductive surgery in PC.…”

Plasma Device Functions and Tissue Effects in the Female Pelvis—A Systematic Review

“…CAP (kINPen) devices aim to trigger biological redox reactions that cause cancer-specific apoptosis or inhibit spread of disease. Furthermore, PAM is under evaluation to reduce post-operative peritoneal adhesions [ 24 ]. It appears that oxygen species are less capable of penetrating tissue than nitrogen species [ 25 ].…”

Human tissue-resident peritoneal macrophages reveal resistance towards oxidative cell stress induced by non-invasive physical plasma

“…Multivariate analysis of spectral data allowed for the biomolecular characterization of cellular structures, including nuclei, proteins and lipids, of PAL-treated macrophages. The potential of Raman imaging to determine PAL-derived changes has already been analyzed in cervical tissue, peritoneal fibroblasts and mesothelial cells ( 6 , 68 ). Proteins and lipids were previously identified as cellular structures most reactive to demonstrate macrophage activation in Raman imaging ( 69 ).…”