TJI. 2021; 9(1): 36-49 | DOI: 10.5222/TJI.2021.29292
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)
, Noor Pramono Noerpramana1
, Yuda Heru Febrianto2
, Widjiati Widjiati3
, Purwati Purwati4
, Suhartono Suhartono5
, Tono Djuwantono6
, Indra Wijaya71
Diponegoro University, Reproductive, Endocrinology, and Fertility Division, Department of Obstetrics and Gynecology, Semarang, Central Java, Indonesia2
Gadjah Mada University, Department of Physiology, Faculty of Veterinary Medicine, Yogyakarta, Indonesia3
Airlangga University, Department of Veterinary Embryology, Faculty of Veterinary Medicine, Surabaya, Indonesia4
Airlangga University, Stem Cell Research and Development Center, Surabaya, Indonesia5
Diponegoro University, Department of Environmental Health, Faculty of Public Health, Semarang, Indonesia6
Padjadjaran University - Dr. Hasan Sadikin Hospital, Department of Obstetrics and Gynecology, Faculty of Medicine, Bandung, Indonesia7
Diponegoro University, Department of Anatomical Pathology, Faculty of Medicine, Semarang, Indonesia
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-α, and endometrial implants in endometriosis mice.Keywords:
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-α 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-α (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-α (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-α (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.
Endometriosis, mesenchymal stem cells, metformin, apoptosis, cell proliferation, endometriosis implants
Inu Mulyantoro, Noor Pramono Noerpramana, Yuda Heru Febrianto, Widjiati Widjiati, Purwati Purwati, Suhartono Suhartono, Tono Djuwantono, Indra Wijaya. 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). TJI. 2021; 9(1): 36-49
Corresponding Author: Inu Mulyantoro, Indonesia