Effect of Adipose-Derived Mesenchymal Stem Cell on the Expressions of Bax/Bcl-2, Ki67, VEGF, TNF-α, and Endometrial Implants in Metformin-Administered Endometriosis Mice (A Mouse Model in Endometriosis Study)

Objective: Endometriosis is a gynecological syndrome that affects many women around the world. The effective management for this illness has not been determined. The aim of this study was to explore the effect of mesenchymal stem cells (MSCs) and metformin on Bax/Bcl-2, Ki67, VEGF, TNF-alpha, and endometrial implants in endometriosis mice. Materials and Methods: Thirty mice with endometriosis were equally divided into 5 experimental groups (S1: 0.1 ml MSCs + 4 mg metformin; S2: 0.1 ml MSCs; S3: 4 mg metformin; S4: 0.1 ml NaCl 9%; and S5: 4 mg metformin + subsequent 0.1 ml MSCs) for 14 days. On the 15th day, peritoneal tissues of mice and endometrial implants were removed to examine the expressions of Bax/Bcl-2, Ki67, VEGF, and TNF-alpha using immunohistochemical staining, and Allred index and endometrial implants using image tracing method with a computer. The obtained data were analyzed using the Kruskal-Wallis and ANOVA tests, followed by the Least Significant Difference (LSD) and Mann-Whitney Post-hoc tests. Results: There were significant differences in the expressions of Bax/Bcl-2 (p=0.002), Ki67 (p=0.004), TNF-alpha (p=0.017), and endometrial implants (p=0.001) in all groups, except for VEGF (p=0.079). The values of S2 didn't differ much compared to the control group (S4) in the Bax/Bcl-2 (p=0.487), TNF-alpha (p=0.191), and endometrial implants (p=0.2). S1 was found to have the highest Bax/Bcl-2 (1.67 +/- 0.845) and lowest TNF-alpha (4.67 +/- 2.15) and endometrial implant (0.86 +/- 2.11). Conclusion: MSCs alone had not any beneficial effect on the treatment of endometriosis, whereas metformin by itself exhibited favorable results. The combination of MSCs and metformin at the same time shows superior outcomes.