Amniotic membrane-derived mesenchymal cells and their conditioned media: potential candidates for uterine regenerative therapy in the horse.
Abstract: Amniotic membrane-derived mesenchymal cells (AMCs) are considered suitable candidates for a variety of cell-based applications. In view of cell therapy application in uterine pathologies, we studied AMCs in comparison to cells isolated from the endometrium of mares at diestrus (EDCs) being the endometrium during diestrus and early pregnancy similar from a hormonal standpoint. In particular, we demonstrated that amnion tissue fragments (AM) shares the same transcriptional profile with endometrial tissue fragments (ED), expressing genes involved in early pregnancy (AbdB-like Hoxa genes), pre-implantation conceptus development (Erα, PR, PGRMC1 and mPR) and their regulators (Wnt7a, Wnt4a). Soon after the isolation, only AMCs express Wnt4a and Wnt7a. Interestingly, the expression levels of prostaglandin-endoperoxide synthase 2 (PTGS2) were found greater in AM and AMCs than their endometrial counterparts thus confirming the role of AMCs as mediators of inflammation. The expression of nuclear progesterone receptor (PR), membrane-bound intracellular progesterone receptor component 1 (PGRMC1) and membrane-bound intracellular progesterone receptor (mPR), known to lead to improved endometrial receptivity, was maintained in AMCs over 5 passages in vitro when the media was supplemented with progesterone. To further explore the potential of AMCs in endometrial regeneration, their capacity to support resident cell proliferation was assessed by co-culturing them with EDCs in a transwell system or culturing in the presence of AMC-conditioned medium (AMC-CM). A significant increase in EDC proliferation rate exhibited the crucial role of soluble factors as mediators of stem cells action. The present investigation revealed that AMCs, as well as their derived conditioned media, have the potential to improve endometrial cell replenishment when low proliferation is associated to pregnancy failure. These findings make AMCs suitable candidates for the treatment of endometrosis in mares.
Publication Date: 2014-10-31 PubMed ID: 25360561PubMed Central: PMC4216086DOI: 10.1371/journal.pone.0111324Google Scholar: Lookup
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Summary
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The research article explores the potential of amniotic membrane-derived mesenchymal cells (AMCs) and their conditioned media as effective candidates for uterine regenerative therapy, particularly in horses with uterine pathologies, by comparing them with cells isolated from the endometrium of mares.
Overview of the Research
- The research primarily focuses on the use of amniotic membrane-derived mesenchymal cells (AMCs) for cell-based applications, specifically for uterine regenerative therapy in mares. The study compares these cells with cells isolated from the endometrium of mares in diestrus termed endometrial diestrus cells (EDCs).
- The researchers focused on how similar the amnion fragments (AM) and endometrial fragments (ED) are on a transcriptional level, examining genes involved in early pregnancy, pre-implantation conceptus development, and their regulators.
- AMCs and AM displayed elevated expression levels of prostaglandin-endoperoxide synthase 2 (PTGS2), an inflammation mediator, when compared to their endometrial counterparts. Other receptors crucial to improved endometrial receptivity exhibited sustained expression in AMCs during multiple in vitro passages, so long as the media was supplemented with progesterone.
Key Findings
- The study’s results showed that soon after isolation, only AMCs expressed Wnt4a and Wnt7a, highlighting their unique transcriptional profile.
- AMCs and their derived conditioned media demonstrated the potential to enhance endometrial cell replenishment, which is crucial when low proliferation correlates to pregnancy failure. This was proven through co-culturing AMCs with EDCs in a transwell system or in the presence of AMC-conditioned medium (AMC-CM), both conditions resulting in a significant increase in EDC proliferation rate due to the action of soluble factors.
- These findings suggest that the AMCs could be effective in the treatment of endometrosis, a uterine pathology that hampers successful conception in mares.
Significance of the Research
- This research offers groundbreaking insight into the potential application of AMCs in the treatment of uterine pathologies in horses. The findings have significant implications, particularly in the veterinary sector, where current therapy options for uterine conditions are limited.
- The research also suggests that the use of AMC-conditioned media could offer an innovative approach to increase endometrial cell proliferation, thereby potentially enhancing pregnancy success rates in mares.
Cite This Article
APA
Corradetti B, Correani A, Romaldini A, Marini MG, Bizzaro D, Perrini C, Cremonesi F, Lange-Consiglio A.
(2014).
Amniotic membrane-derived mesenchymal cells and their conditioned media: potential candidates for uterine regenerative therapy in the horse.
PLoS One, 9(10), e111324.
https://doi.org/10.1371/journal.pone.0111324 Publication
Researcher Affiliations
- Department of Life and Environmental Sciences, Università Politecnica delle Marche, Ancona, Italy.
- Department of Life and Environmental Sciences, Università Politecnica delle Marche, Ancona, Italy.
- Department of Life and Environmental Sciences, Università Politecnica delle Marche, Ancona, Italy.
- Department of Life and Environmental Sciences, Università Politecnica delle Marche, Ancona, Italy.
- Department of Life and Environmental Sciences, Università Politecnica delle Marche, Ancona, Italy.
- Large Animal Hospital, Reproduction Unit, Università degli Studi di Milano, Lodi, Italy.
- Large Animal Hospital, Reproduction Unit, Università degli Studi di Milano, Lodi, Italy; Department of Veterinary Science for Animal Health, Production and Food Safety, Università degli Studi di Milano, Milan, Italy.
- Large Animal Hospital, Reproduction Unit, Università degli Studi di Milano, Lodi, Italy.
MeSH Terms
- Amnion / cytology
- Animals
- Cell Proliferation
- Culture Media, Conditioned
- Endometrium / cytology
- Female
- Horses
- Mesenchymal Stem Cells / cytology
- Pregnancy
- Regeneration
- Uterus / cytology
- Uterus / physiology
Conflict of Interest Statement
The authors have declared that no competing interests exist.
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