Adipose derived mesenchymal stem cell treatment in experimental asherman syndrome induced rats

Mol Biol Rep. 2020 Jun;47(6):4541-4552. doi: 10.1007/s11033-020-05505-4. Epub 2020 May 22.

Abstract

Asherman syndrome (AS) occurs due to fibrosis or uterine adhesions as a result of damage to the basal layer of the endometrium. The aim of this study is investigating the effects of adipose tissue-derived mesenchymal stem cell (ADMSC) application on the expression of vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF-1), miRNA-98, miRNA199a in endometrial tissue in rats with AS. Study groups were designed as, control (C), Asherman syndrome (AS), AS + oral estrogen (ASO), AS + ADMSC (ASSC), AS + oral estrogen + ADMSC (ASSCO) with 7 samples in each group. Characterization and differentiation experiments were performed in ADMSC obtained. Two weeks after the development of the AS, ADMSC therapy was applied. BrdU (5-bromo-2'-deoxyuridine) labeling was performed to show the presence of ADMSC in the tissues. Rats were sacrificed after 8 weeks and bilateral uterine horn resection was performed. Tissues were fixed in formaldehyde. After routine tissue follow-up, sections were taken and evaluated with hematoxylin eosin staining. VEGF1 and IGF1 expressions were evaluated by immunohistochemical staining and western blot analysis. Expression changes of miR-98 and miR-199a were detected by RT-PCR. Our results showed that stem cells and estrogen giving together reduced inflammation and fibrosis in the endometrium. Immunohistochemistry and western blot results suggested that this effect was achieved especially through IGF-1. In our study, decreased miR-98 and miR-199a expressions were determined in Asherman syndrome. Furthermore, no changes of miRNA expressions were observed in treatment groups.

Keywords: Asherman syndrome; IGF-1; Mesenchymal stem cells; VEGF; miR-199a; miR-98.

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • Endometrium / drug effects
  • Endometrium / metabolism*
  • Estrogens / pharmacology
  • Female
  • Fibrosis / metabolism
  • Gynatresia / metabolism
  • Gynatresia / therapy*
  • Insulin-Like Growth Factor I / metabolism
  • Mesenchymal Stem Cell Transplantation / methods
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Rats
  • Rats, Wistar
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Estrogens
  • MIRN199 microRNA, rat
  • MIRN98 microRNA-98, rat
  • MicroRNAs
  • Vascular Endothelial Growth Factor A
  • Insulin-Like Growth Factor I