Effects of adipose tissue-derived mesenchymal stem cells and/or sildenafil citrate in experimental colon anastomosis model

Abstract

BACKGROUND: This study aimed to evaluate the healing effects of adipose tissue-derived mesenchymal stem cells (AT-MSC) and sildenafil citrate alone or in combination of colon anastomosis experimental model. METHODS: A total of 40 female Wistar rats were randomly distributed to four groups: Control (without any intervention post-anastomosis), stem cell (AT-MSC injection on the anastomosis site), SIL (oral gavage of 10 mg/kg sildenafil citrate), and stem cell + SIL (AT-MSC injection and oral administration of sildenafil citrate) groups. Rats were euthanized 5 days post-anastomosis. Intra-abdominal adhesion status and anastomotic burst pressure were measured to assess anastomotic healing. Hydroxyproline and TNF-α level, neutrophil leukocyte infiltration, epithelial regeneration, and necrosis in the anastomosis tissue were examined. RESULTS: Anastomosis leakage and anastomosis burst pressure were not different among the groups. Treatment with sildenafil, stem cell, and stem cell + SIL reduced the degree of perianastomotic adhesions compared to control (p<0.05). A significant increase was noted in hydroxyproline in the stem cell and stem cell + SIL groups (p=0.001). AT-MSC injection alone or in combination with sildenafil citrate reduced the TNF-α concentration at the anastomosis site (p=0.001). Histopathological examination revealed that all treatments enhanced the clearance of the necrotic debris, reduced leukocytes infiltration, and accelerated the retraction of anastomosed ends except control (p=0.001). Epithelial regeneration was more pronounced in the stem cell group than other groups (p=0.001). Macrophage density was lower in groups treated with the SIL or stem cell groups than the control and stem cell + SIL groups (p=0.001). CONCLUSION: Sildenafil citrate and/or AT-MSC in the anastomosed rats promoted the anastomosis healing that was more pronounced in groups receiving stem cell injections.