Adipose-derived mesenchymal stromal cell transplantation at the graft site improves the structure and function of autografted mice ovaries: a stereological and biochemical analysis

Cytotherapy. 2018 Nov;20(11):1324-1336. doi: 10.1016/j.jcyt.2018.09.006. Epub 2018 Oct 22.

Abstract

Background: Ovarian tissue autografting is a fertility restoration technique that is frequently used in young women with cancer who undergo radio/chemotherapy. A limiting factor in this technique is ischemia-reperfusion (I/R) damage. Because adipose-derived mesenchymal stromal cells (ADMSCs) protect different ischemic tissues against I/R damage, we examined the effect of ADMSC transplantation at the graft site in mice ovary autografting.

Method: Mice were divided into three groups: control, autograft and autograft + ADMSCs. Seven days after ovary autografting and ADMSC transplantation, serum superoxide dismutase (SOD) activity, total antioxidant capacity, serum concentrations of malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), interleukin (IL)-6 and IL-10 were measured. After 28 days, ovary histology, serum concentrations of progesterone and estradiol and apoptosis rate were also estimated. At 1-3 and 28 days post-ovary autografting and ADMSC transplantation, angiogenesis was detected. The results were analyzed using one-way analysis of variance (ANOVA) and Tukey test, and the means were significantly different at P ≤ 0.05.

Result: In the autograft + ADMSCs group, the total volume of the ovary, cortex and medulla (P ≤ 0.001), the number of follicles, SOD activity, IL-10 (P ≤ 0.001) and progesterone and estradiol (P ≤ 0.01) concentrations significantly increased compared with the autograft group. Apoptosis rate, IL-6, TNFα and MDA concentrations in the autograft + ADMSCs group were lower than the autograft group (P ≤ 0.001). The angiogenesis was accelerated and the localization of CD31-positive cells in the cortex was similar to the control group following ADMSC transplantation.

Discussion: ADMSC transplantation enhances the structure and function of grafted ovary.

Keywords: adipose-derived mesenchymal stromal cells; apoptosis; inflammation; mouse; ovarian transplantation; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Apoptosis
  • Estradiol / blood
  • Female
  • Ischemia
  • Malondialdehyde / blood
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / physiology
  • Mice
  • Neovascularization, Physiologic
  • Ovary / blood supply
  • Ovary / physiology*
  • Ovary / transplantation*
  • Oxidative Stress
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Transplantation, Autologous
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Pecam1 protein, mouse
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Tumor Necrosis Factor-alpha
  • Estradiol
  • Malondialdehyde