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PloS one2014; 9(6); e97889; doi: 10.1371/journal.pone.0097889

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

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.
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Publication Date: 2014-06-05 PubMed ID: 24901368PubMed Central: PMC4046935DOI: 10.1371/journal.pone.0097889Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study evaluates the impact of using mesenchymal stem cell infusion to treat endometrosis in horses, which is a condition where certain changes in the expression of proteins in the uterus lead to infertility. The researchers found that the treatment had positive effects in modulating the expression of these proteins and encouraging cell growth.

Objective of the Study

  • The primary goal of this research was to assess the effects of using adipose tissue-derived multipotent mesenchymal stem cells (eAT-MSCs) from horses to treat equine endometrosis, a degenerative disease causing infertility. This condition is characterized by changes in the expression pattern of certain endometrial proteins, and as of now, there is no effective treatment available for it.
  • The researchers were also interested in determining whether these eAT-MSCs can induce endometrial tissue remodeling in mares with endometrosis. As such, they examined the expression patterns of these proteins after the eAT-MSC infusion.

Methodology

  • The team used a transplant approach where they infused eAT-MSC into the uterus of affected mares, while the control animals received a placebo treatment.
  • This study involved taking uterine biopsy samples before and after cells transplantation. The “after” samples were collected at days 7, 21, and 60 post-transplantation for analysis.

Analysis

  • The researchers performed both conventional histopathology and expression analysis of specific proteins, such as laminin, vimentin, Ki-67-antigen, α-smooth muscle actin (α-SMA), and cytokeratin 18 (CK18) present in the endometrium, before and after the transplant.
  • By analyzing these protein expressions, researchers were looking at early signs of endometrial tissue remodeling. These are changes believed to bring about a positive transformation in the cellular and glandular constructs of the tissue affected by endometrosis.

Findings

  • The study revealed that eAT-MSCs did initiate early remodeling of endometrial tissue microenvironment. This was marked by alterations observed in the intra cellular and intra glandular localizations of the proteins under study as early as day 7.
  • More importantly, the infused eAT-MSCs were found capable of positively modulating the expression pattern of the secretory proteins being examined. These cells also promoted the induction of glandular epithelial cells proliferation. These outcomes suggest local benefits to the affected endometrial tissue environment after eAT-MSCs transplantation.

Cite This Article

APA
Mambelli LI, Mattos RC, Winter GH, Madeiro DS, Morais BP, Malschitzky E, Miglino MA, Kerkis A, Kerkis I. (2014). Changes in expression pattern of selected endometrial proteins following mesenchymal stem cells infusion in mares with endometrosis. PLoS One, 9(6), e97889. https://doi.org/10.1371/journal.pone.0097889

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 9
Issue: 6
Pages: e97889
PII: e97889

Researcher Affiliations

Mambelli, Lisley I
  • Laboratório de Genética, Instituto Butantan, São Paulo, SP, Brasil; Programa de Pós-Graduação em Anatomia dos Animais Domésticos e Silvestres da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo, São Paulo, SP, Brasil.
Mattos, Rodrigo C
  • Reprolab, Faculdade de Medicina Veterinária, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.
Winter, Gustavo H Z
  • Reprolab, Faculdade de Medicina Veterinária, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.
Madeiro, Dener S
  • Laboratório de Genética, Instituto Butantan, São Paulo, SP, Brasil.
Morais, Bruna P
  • Laboratório de Genética, Instituto Butantan, São Paulo, SP, Brasil.
Malschitzky, Eduardo
  • Curso de Medicina Veterinária, ULBRA, Canoas, RS, Brasil.
Miglino, Maria Angélica
  • Programa de Pós-Graduação em Anatomia dos Animais Domésticos e Silvestres da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo, São Paulo, SP, Brasil.
Kerkis, Alexandre
  • Laboratório de Genética, Instituto Butantan, São Paulo, SP, Brasil.
Kerkis, Irina
  • Laboratório de Genética, Instituto Butantan, São Paulo, SP, Brasil.

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

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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Citations

This article has been cited 24 times.
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