Changes in expression pattern of selected endometrial proteins following mesenchymal stem cells infusion in mares with endometrosis

PLoS One. 2014 Jun 5;9(6):e97889. doi: 10.1371/journal.pone.0097889. eCollection 2014.

Abstract

Mesenchymal stem cells (MSCs) due to their self-renewal potential and differentiation capacity are useful for tissue regeneration. Immunomodulatory and trophic properties of MSCs were demonstrated suggesting their use as medicinal signaling cells able to positively change local environment in injured tissue. Equine endometrosis is a progressive degenerative disease responsible for glandular alterations and endometrial fibrosis which causes infertility in mares. More precisely, this disease is characterized by phenotypic changes in the expression pattern of selected endometrial proteins. Currently, no effective treatment is available for endometrosis. Herein, we aimed at the evaluation of expression pattern of these proteins after allogeneic equine adipose tissue-derived multipotent mesenchymal stem cells (eAT-MSCs) infusion as well as at testing the capacity of these cells to promote endometrial tissue remodeling in mares with endometrosis. eAT-MSC (2 × 10(7)/animal) were transplanted into mares' uterus and control animals received only placebo. Uterine biopsies were collected before (day 0) and after (days 7, 21 and 60) cells transplantation. Conventional histopathology as well as expression analysis of such proteins as laminin, vimentin, Ki-67-antigen, α-smooth muscle actin (α-SMA) and cytokeratin 18 (CK18) have been performed before and after eAT-MSCs transplantation. We demonstrated that eAT-MSCs induced early (at day 7) remodeling of endometrial tissue microenvironment through changes observed in intra cellular and intra glandular localization of aforementioned proteins. We demonstrated that eAT-MSCs were able to positively modulate the expression pattern of studied secretory proteins as well as, to promote the induction of glandular epithelial cells proliferation suggesting local benefits to committed endometrial tissue environment after eAT-MSCs transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Biopsy
  • Endometriosis / genetics*
  • Endometriosis / pathology*
  • Endometriosis / therapy
  • Endometrium / metabolism
  • Endometrium / pathology
  • Female
  • Gene Expression Profiling
  • Horses
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / metabolism*
  • Mucous Membrane / metabolism
  • Mucous Membrane / pathology
  • Transcriptome*

Substances

  • Biomarkers

Grants and funding

This work was supported by the Sao Paulo Research Foundations (Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP. Grant numbers: 2006/51839-7(PIPE); 2007/50212-3 (BP.IC); 2009/06764-7 (BP.MS)) and Coordination of Improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – CAPES) – fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.