Human umbilical cord blood-mesenchymal stem cells transplantation renovates the ovarian surface epithelium in a rat model of premature ovarian failure: Possible direct and indirect effects

Tissue Cell. 2016 Aug;48(4):370-82. doi: 10.1016/j.tice.2016.05.001. Epub 2016 May 10.

Abstract

This study aimed to isolate mesenchymal stem cells (MSC) from human umbilical cord blood (HCB) and to explore their influence on the ovarian epithelium after paclitaxel-induced ovarian failure. Ninety-five rats were divided into 6 groups: control, paclitaxel, paclitaxel and saline, HCB-MSC-treated for 2 weeks, HCB-MSC-treated for 4 weeks, and HCB-MSC-treated for 6 weeks. HCB cells were studied for CD34, CD44, and Oct ¾ using flow cytometry. Serum levels of FSH and E2 were measured using ELISA, RT-PCR analysis for human gene; beta-actin (ACTB), immunohistochemical analysis for CK 8/18, TGF-ß, PCNA and CASP-3 were performed. We found that ACTB gene was expressed in all rats' ovaries received HCB-MSC. After 4 weeks of transplantation, there was significant reduction in FSH, elevation in E2 levels, stabilization of the surface epithelium morphostasis, an increase in the antral follicle count and increase in integrated densities (ID) of CK 8/18, TGF-ß, and PCNA expressions and decrease in ID of CASP-3 expression. We concluded that HCB-MSC can restore the ovarian function after paclitaxel injection through a direct triggering effect on the ovarian epithelium and/or indirect enrichment of ovarian niche through regulating tissue expression of CK 8/18, TGF-ß and PCNA. These molecules are crucial in regulating folliculogenesis and suppressing CASP-3-induced apoptosis.

MeSH terms

  • 12E7 Antigen / blood
  • Actins / biosynthesis
  • Actins / genetics
  • Animals
  • Apoptosis / genetics
  • Caspase 3 / genetics
  • Cord Blood Stem Cell Transplantation*
  • Female
  • Follicle Stimulating Hormone / blood
  • Gene Expression Regulation
  • Humans
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Ovary / drug effects
  • Ovary / growth & development*
  • Ovary / pathology
  • Paclitaxel / toxicity
  • Primary Ovarian Insufficiency / blood
  • Primary Ovarian Insufficiency / chemically induced
  • Primary Ovarian Insufficiency / pathology
  • Primary Ovarian Insufficiency / therapy*
  • Rats
  • Transforming Growth Factor beta / biosynthesis*
  • Transforming Growth Factor beta / genetics

Substances

  • 12E7 Antigen
  • Actins
  • Transforming Growth Factor beta
  • Follicle Stimulating Hormone
  • Caspase 3
  • Paclitaxel