51. Alpha-1-antitrypsin improves anastomotic healing in intestinal epithelial cells model.
- Author
-
Schukfeh N, Sivaraman K, Schmidt A, Vieten G, Dingemann J, Weidner J, Olmer R, and Janciauskiene S
- Subjects
- Humans, Epithelial Cells drug effects, Intestinal Mucosa drug effects, Cells, Cultured, alpha 1-Antitrypsin genetics, alpha 1-Antitrypsin pharmacology, Cell Proliferation drug effects, Wound Healing drug effects, Anastomosis, Surgical
- Abstract
Purpose: Intestinal anastomosis is a routine procedure in pediatric surgery, with leakage being a significant complication. Human alpha1-antitrypsin (AAT), whose physiological serum concentrations range from 0.9-2.0 mg/ml, is known to accelerate wound healing and stimulate the expression of cell proliferation-related genes. We hypothesized that AAT might enhance anastomotic healing., Methods: In a monolayer of non-tumorigenic HIEC-6 epithelial cells derived from fetal intestine a scratch was created. Standard medium without (control) or with AAT (0.5 and 1 mg/ml) was added. Cells were observed using a Life-Cell Imaging System. Cell proliferation was assessed, and the expression of proliferation-related genes was measured by qRT-PCR., Results: In the presence of AAT, the scratch closed significantly faster. Cells treated with 1 mg/ml AAT showed 53% repopulation after 8 h and 97% after 18 h, while control cells showed 24% and 60% repopulation, respectively (p < 0.02). The treatment with AAT induced HIEC-6-cell proliferation and significantly increased the mRNA-expression of CDKN1A, CDKN2A, ANGPTL4, WNT3 and COL3A1 genes. AAT did not change the mRNA-expression of CXCL8 but decreased levels of IL-8 as compared to controls., Conclusion: At physiological concentrations AAT accelerates the confluence of intestinal cells and increases cell proliferation. The local administration of AAT may bear therapeutic potential to improve anastomotic healing., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2024
- Full Text
- View/download PDF