17β-estradiol protects human eyelid-derived adipose stem cells against cytotoxicity and increases transplanted cell survival in spinal cord injury

J Cell Mol Med. 2014 Feb;18(2):326-43. doi: 10.1111/jcmm.12191. Epub 2013 Dec 22.

Abstract

Stem cell transplantation represents a promising strategy for the repair of spinal cord injury (SCI). However, the low survival rate of the grafted cells is a major obstacle hindering clinical success because of ongoing secondary injury processes, which includes excitotoxicity, inflammation and oxidative stress. Previous studies have shown that 17b-estradiol (E2) protects several cell types against cytotoxicity. Thus, we examined the effects of E2 on the viability of human eyelid adipose-derived stem cells (hEASCs) in vitro with hydrogen peroxide (H₂O₂)-induced cell model and in vivo within a rat SCI model. Our results showed that E2 protected hEASCs against H₂O₂-induced cell death in vitro, and enhanced the survival of grafted hEASCs in vivo by reducing apoptosis. Additionally, E2 also enhanced the secretion of growth factors by hEASCs, thereby making the local microenvironment more conducive for tissue regeneration. Overall, E2 administration enhanced the therapeutic efficacy of hEASCs transplantation and facilitated motor function recovery after SCI. Hence, E2 administration may be an intervention of choice for enhancing survival of transplanted hEASCs after SCI.

Keywords: 17-β-estradiol; cell transplantation; hEASCs; spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Adipose Tissue / immunology
  • Animals
  • Apoptosis / drug effects
  • Estradiol / pharmacology*
  • Eyelids / cytology
  • Eyelids / immunology
  • Graft Survival / drug effects*
  • Graft Survival / immunology
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Intercellular Signaling Peptides and Proteins / biosynthesis
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Spinal Cord Injuries / immunology
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / therapy*
  • Stem Cell Transplantation*
  • Stem Cells / cytology
  • Stem Cells / drug effects*
  • Stem Cells / immunology
  • Transplantation, Heterologous
  • Treatment Outcome

Substances

  • Intercellular Signaling Peptides and Proteins
  • Estradiol
  • Hydrogen Peroxide