Preperitoneal Fat Grafting Inhibits the Formation of Intra-abdominal Adhesions in Mice

Abstract

Background Adhesion formation contributes to postoperative complications in abdominal and gynaecological surgery. Thus far, the prevention and treatment strategies have focused on mechanical barriers in solid and liquid form, but these methods are not in routine use. As autologous fat grafting has become popular in treatment of hypertrophic scars because of its immunomodulatory effects, we postulated that fat grafting could also prevent peritoneal adhesion through similar mechanisms. Methods This was a control versus intervention study to evaluate the effect of fat grafting in the prevention on peritoneal adhesion formation. An experimental mouse model for moderate and extensive peritoneal adhesions was used (n = 4-6 mice/group). Adhesions were induced mechanically, and a free epididymal fat graft from wild type or CAG-DsRed mice was injected preperitoneally immediately after adhesion induction. PET/CT imaging and scaling of the adhesions were performed, and samples were taken for further analysis at 7 and 30 days postoperation. Macrophage phenotyping was further performed from peritoneal lavage samples, and the expression of inflammatory cytokines and mesothelial layer recovery were analysed from peritoneal tissue samples. Results Fat grafting significantly inhibited the formation of adhesions. PET/CT results did not show prolonged inflammation in any of the groups. While the expression of anti-inflammatory and anti-fibrotic IL-10 was significantly increased in the peritoneum of the fat graft-treated group at 7 days, tissue-resident and repairing M2 macrophages could no longer be detected in the fat graft at this time point. The percentage of the continuous, healed peritoneum as shown by Keratin 8 staining was greater in the fat graft-treated group after 7 days. Conclusions Fat grafting can inhibit the formation of peritoneal adhesions in mice. Our results suggest that fat grafting promotes the peritoneal healing process in a paracrine manner thereby enabling rapid regeneration of the peritoneal mesothelial cell layer.

Small Bowel Obstruction Induced by Concurrent Postoperative Intra-Abdominal Adhesions and Small Bowel Fecal Materials in a Young Dog

“…Owing to this high prevalence of recurrence, extensive research for preventing re-adhesion has been conducted, but no clinical standard has been established for any preventive modalities, either surgical or pharmacological [ 13 , 34 ]. As one of these preventive modalities, barriers, which are a kind of a membrane or gel developed to separate the damaged serosal surfaces from the adjacent organs [ 3 , 20 ], have been demonstrated to be effective in animal models and clinical trials [ 3 , 20 , 34 ]. Most recently, APG was demonstrated to have a preventive effect on peritoneal adhesion by transplanting mesothelial cells and rapid reperitonealization [ 34 ].…”

“…They reported that the mesothelial cells were detected 14 days after APGs were transplanted with the mesothelial cell side exposed to the abdominal cavity, but were not detected when the submesothelial layer was exposed to the abdominal cavity [ 34 ]. Although the preventive effect of APGs on serosal re-adhesion has been proven in human patients and in rat and mouse models [ 3 , 20 , 34 ], an additional randomized, prospective study is necessary in order to establish the evidence of the prophylactical application of APGs in canine patients.…”

“…Postoperative intra-abdominal adhesions (PIAs) are inevitable complications of major abdominal surgery in both humans and animals, with various extents of adhesion formation depending on the patient [ 1 , 2 , 3 ]. Among human patients, up to 93% develop intra-abdominal adhesions postoperatively, and up to 10% who underwent laparotomy presented with adhesions related to complications such as small-bowel obstruction (SBO) [ 4 ].…”

Mechanisms of Peritoneal Mesothelial Cells in Peritoneal Adhesion

“…Finding the initiating factors of the inflammatory response and fibrin deposition is crucial, as this may be beneficial in controlling the formation of PAs at the source. To sum up, the formation of PAs may be a result of the overall effects of the inflammatory response, coagulation, fibrin deposition and extracellular matrix (ECM) generation [ 41 ]. Although immune cells such as neutrophils [ 42 , 43 ], macrophages [ 40 , 44 , 45 ], mast cells [ 46 ], and T lymphocytes [ 47 , 48 ] are also involved, damage to PMCs and the exposure of the basement membrane are necessary for these cells to promote PA formation [ 49 ].…”

“…In addition, rat bone marrow mesenchymal stem cells were found to reduce inflammation and fibrosis by repairing PMCs [ 114 ]. Autologous fat transplantation has an immunomodulatory effect and can be used to treat hypertrophic scars and prevent PA formation [ 41 ]. There is strong evidence that fat transplantation prevents the occurrence of PAs by promoting the rapid regeneration of damaged PMCs.…”