Tracking of human embryonic stem cell-derived mesenchymal stem cells in premature ovarian failure model mice

Biochem Biophys Res Commun. 2021 Nov 5;577:6-11. doi: 10.1016/j.bbrc.2021.08.063. Epub 2021 Aug 26.

Abstract

Premature ovarian failure (POF) is defined by amenorrhea, hypoestrogenism, elevated gonadotropin levels, and infertility. Chemotherapeutic agents are the most gonadotoxic agents that lead to POF. Although some previous studies have presented that mesenchymal stem cells (MSCs) transplantation could rescue the ovary function of POF animal models through the paracrine pathway, these mechanisms require further investigation. However, mechanisms of embryonic stem cell-derived MSCs (ES-MSCs) therapeutic effects on POF animal models have not been fully investigated yet. This study aimed to evaluate the migration and distribution of ES-MSCs in a model of chemotherapy-induced POF. Female mice received intraperitoneal injections of cyclophosphamide (Cy) to induce POF. Then, MSCs were labeled with green fluorescent protein (GFP) in vitro and injected intravenously into POF mice, and the distribution of MSCs was dynamically monitored at 1 week after transplantation. We harvested the lungs, liver, spleen, ovaries, heart, and kidneys 1 week after transplantation. The sections of these tissues were observed under the fluorescent microscope. More than 70% MSCs were successfully labeled with GFP at 72 h after labeling. MSCs were uniformly distributed in multiple organs and tissues including lungs, liver, spleen, ovaries, heart, and kidneys of POF mice. In mice, at 1week after intravenous transplantation, GFP labeled ES-MSCs were observed in the lungs, liver, spleen, ovaries, heart, and kidneys of POF mice, and the number of GFP labeled ES-MSCs in lungs, ovaries, and heart were higher than that in the spleen, kidneys, and liver. Our results revealed intravenously implanted ES-MSCs could migrate into the various tissues in chemotherapy-induced damaged POF mice.

Keywords: Cyclophosphamide; Green fluorescent protein; Mesenchymal stem cell; Premature ovarian failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Movement
  • Cell Tracking / methods
  • Cells, Cultured
  • Cyclophosphamide
  • Disease Models, Animal*
  • Female
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Human Embryonic Stem Cells / cytology
  • Human Embryonic Stem Cells / metabolism*
  • Humans
  • Lung / cytology
  • Lung / metabolism
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence / methods
  • Myocardium / cytology
  • Myocardium / metabolism
  • Ovary / cytology
  • Ovary / metabolism
  • Primary Ovarian Insufficiency / chemically induced
  • Primary Ovarian Insufficiency / metabolism
  • Primary Ovarian Insufficiency / therapy*

Substances

  • Green Fluorescent Proteins
  • Cyclophosphamide