Comparison of the effects of adipose tissue mesenchymal stem cell and sildenafil citrate application in an experimental colon anastomosis model

Introduction and Purpose: Colon anastomoses play an important role in gastrointestinal system surgery. Anastomotic leakage, which is a common complication, causes serious mortality and morbidity. Minimizing the rate of anastomotic leakage will reduce the mortality and morbidity rate and their burden on the health system. There are many studies in the literature investigating various methods that may contribute to wound healing in the intestinal tract. There are many studies about the effects of stem cells to wound healing while there are only a limited number of studies on the effects of colonic anastomosis. In addition to the few studies on the effect of sildenafil citrate on colon anastomosis healing, no studies have been performed in which stem cell and sildenafil citrate are applied together. For this reason, we investigated the effects of stem cell and sildenafil citrate applications on colon anastomosis healing. Materials and Methods:In this study, 44 Wistar-Albino rats were used. Four of these rats were used to obtain mesenchymal stem cells. The other 40 rats were randomly divided into 4 equal groups, each consisting of 10 rats: Group 1; Control, Group 2; Sildenafil Citrate, Group 3; Stem Cell, Group 4; Stem Cell + Sildenafil Citrate. All rats were operated by the same surgeon on the scheduled day with appropriate conditions. Descending colon was cut in all rats and single-layer anastomosis was performed between both ends. Oral sildenafil citrate treatment was applied once daily to 10 mg/kg/day for two days before the operation and five days after the operation.In the stem cell groups, 0,1 ml of subserosal and 0,2 ml of total stem cells were injected during operation. (4x105 stem cells per 0,1 ml). All rats were sacrificed on postoperative fifth day, intraabdominal adhesions of rats, anastomosis bursting pressures, anastomosis leakage, reepithelization, neutrophil leukocyte infiltration, necrosis density, macrophage density, distance between wound lips, granulation tissue thickness, hydroxyproline, myeloperoxidase, nitric oxide, tumor necrosis factor-α and vascular endothelial growth factor were evaluated. Results:There was no significant difference between the groups in terms of anastomosis burst pressures (p:0,52). Anastomotic leakage was not observed in the stem cell groups whereas anastomotic leakage was observed in the other groups. Significant difference was observed in terms of intraabdominal adhesion (p:0,043). In the control group, a better adhesion was observed in the two groups treated with stem cells (Group 3 and 4). When hydroxyproline and TNF-α levels were compared, hydroxyproline and TNF-α levels were found to be higher in two groups treated with stem cells (Group 3 and 4) than in the other two groups (Groups 1 and 2) and the difference was statistically significant (p:0,001). There was no significant effect of sildenafil citrate administration. Nitric oxide levels were found to be significantly different between the groups (p:0,01). The amount measured in Group 4 treated with both stem cell and sildenafil citrate was higher than that of the other three groups. VEGF levels were not studied in any group. Myeloperoxidase levels were significantly different between the groups (p:0,001), the highest in Group 4 and the lowest in Group 2. The best reepithelialization was observed in Group 3 (p:0,001). The amount of necrosis, PMNL infiltration and granulation tissue thickness were lowest in Group 3 and Group 4 (p:0,001 for each). Macrophage density was lowest in Group 2 and Group 3 (p:0,001). The distance between the wound ends was minimum in Group 3 and at maximum in Group 1 (p:0,001). Conclusion:As a result of this study, we think that mesenchymal stem cell application in colon anastomoses contributes to wound healing positively. Further studies are necessary to clarify the positive or negative effects of sildenafil citrate administration on wound healing in colon anastomosis. Keywords: Stem cell, Sildenafil citrate, Colonic anastomosis, Wound healing.