Endometriotic Stem Cells Research Articles

Effects of Exosomes from Menstrual Blood-derived Stem Cells and Ginger on Endometriotic Stem Cells.

Menstrual blood-derived stem cells from endometriosis patients (E-MenSCs) have different gene expression patterns than those from healthy nonendometriotic females (NE-MenSCs). Exosomes extracted from mesenchymal stem cells and plants are considered for the treatment of various diseases. This study aimed to compare the effects of exosomes derived from NE-MenSCs (C-exos) and those from the roots of ginger (P-exos) on E-MenSCs. E-MenSCs at the third passage were used, and after evaluating the effective dosage with MTT, C-exos (200 µg/mL) or P-exos (100 µg/mL) were added to treat them. Following a 72-h incubation, the cells were analyzed with annexin V/PI test to evaluate the apoptosis rate. Also, genes related to inflammation (IL-6, IL-8, IL-1β, NF-κB, COX2), cell cycle (Cyclin D1), the steroid pathway (ESR1), migration and invasion (MMP-2, MMP-9, VEGF), and the apoptosis pathway (BAX, BCL2) were detected by real-time PCR. Apoptosis was increased in both the P- and C-exos groups. The expression levels of IL-6 and IL-1β were significantly lower in the P-exos group than in the E-MenSCs group. The expression levels of IL-8, NF-κB, COX-2, and MMP-9 were significantly decreased in both the P-exos group and the C-exos group. The expression level of VEGF was significantly lower in the P-exos group than in the E-MenSCs group. The BAX/BCL2 ratio was much lower in the P-exos group than in the E-MenSCs group. In this study, we established the feasibility of using a novel natural nontoxic material to target endometriotic mesenchymal stem cells to modify their gene expression and function toward healthy cells. Both C-exos and P-exos showed positive effects on the gene expression and function of endometriotic cells. Considering that plant exosomes are easier to access and less expensive, they can be considered for clinical use in improving the symptoms of endometriosis patients.

Promising effects of exosomes from menstrual blood-derived mesenchymal stem cells on endometriosis

Endometriosis as a non-malignant gynecological disease leads to dysregulation of numerous cellular functions including apoptosis, angiogenesis, migration, proliferation, and inflammation. Accumulating evidence has shed light on the importance of endometrial stem cells within the menstrual blood which are involved in the establishment and progression of endometriotic lesions in a retrograde manner. According to the fact that the therapeutic benefits of mesenchymal stem cells are provided through paracrine functions, we used exosomes from menstrual blood-derived stem cells (MenSCs) for treating endometriotic stem cells to inhibit their lesion formation tendency. Menstrual blood samples from healthy and endometriosis women were collected. Isolated MenSCs by the density-gradient centrifugation method were characterized by flow cytometry. Secreted exosomes were isolated from healthy MenSCs (NE-MenSCs) and used to treat endometriotic cells (E-MenSCs). 72 h after treatment, different mechanisms and pathways including inflammation, proliferation, apoptosis, migration, and angiogenesis were analyzed using Real-Time PCR, ELISA, immunocytochemistry, annexin V/PI, and scratching assay. Exosome treatment significantly reduce the expression level of markers related to inflammation, proliferation, migration, and angiogenesis in E-MenSCs which are aberrantly expressed in endometriosis. Moreover, apoptosis was induced in E-MenSCs after treatment which was evaluated in both gene and protein levels. In this study, we give preliminary evidence for the potential of MenSCs-Exo in ameliorating endometriosis. Regarding our results, we suggest that after relevant clinical trial, MenSCs-derived exosomes can be considered as a better treatment option to improve endometriosis compared to common and conventional treatments and show their potential as a cell-free product in endometriosis repair.

Deregulation of Stemness-Related Genes in Endometriotic Mesenchymal Stem Cells: Further Evidence for Self-Renewal/Differentiation Imbalance

Background:Any irregularities in self-renewal/differentiation balance in endometriotic MSCs can change their fate and function, resulting in endometriosis development. This study aimed to evaluate the expression of OCT4 transcripts (OCT4A, OCT4B, and OCT4B1), SOX2, and NANOG in endometriotic MSCs to show their aberrant expression and to support self-renewal/differentiation imbalance in these cells. Methods:MSCs were isolated from three endometriotic and three normal endometrium samples and characterized and analyzed for the expressions of OCT4A, OCT4B, OCT4B1, SOX2, and NANOG using the qRT-PCR. Results:The expressions of OCT4 transcripts and NANOG increased significantly in endometriotic MSCs, whereas SOX2 expression did not show any significant difference. Conclusion:Our findings provide further evidence for confirming the self-renewal/ differentiation imbalance in endometriotic MSCs, as the main underlying cause of endometriosis development. This study also paves the way for further research on endometriosis treatment by focusing on endometriotic stem cells.

Feasibility of serum-free culture in isolating endometriotic stem cells

Objective: To explore a novel approach for the isolation of human endometriotic stem cells for further study in the stem cell theory of endometriosis. Materials and Methods: A serum-free medium (SFM) was used to isolate the stem cells from ectopic endometrium, eutopic endometrium, and normal endometrium in vitro, and the biological properties including clonogenicity, multipotency, and invasive ability were examined and compared. Results: The ectopic endometrium-derived stem cells cultured in SFM showed higher cloneforming efficiency and sphere formation efficiency (SFE) than eutopic endometrium and normal endometrium, they all can differentiate to endothelial cell and fibroblast, and the ectopic endometrium-derived stem cells also have stronger invasive ability than eutopic endometrium-derived and normal endometrium-derived stem cells. Conclusion: According to the results of the present study, the authors can conclude that human endometriotic stem cells can be isolated in SFM effectively and ectopic endometrium-derived stem cells are probably associated with endometriosis.

The immunological impact of orthomolecular medicine using bioactive compounds as key factors in endometriosis

Background: Endometriosis, an inflammatory, non-lethal, non-malignant disease, still has unjustified etiology. Among many, the theory dealing with this review claims that a suppressed or incompetent immune system that is totally unable to eradicate the non-hemopoietic mesenchymal endometriotic stem cell (MESC) escapes immune surveillance. As a result, there is migration and invasion of the aforementioned cell to ectopic tissues causing the disease. Keywords: bioactive compounds, functional foods, endometriosis, orthomolecular medicine, mesenchymal endometriotic stem cell (MESC), immune system

Endometriotic Mesenchymal Stem Cells Epigenetic Pathogenesis: Deregulation of miR-200b, miR-145, and let7b in A Functional Imbalanced Epigenetic Disease.

Objective Stem cell issue is a strong theory in endometriosis pathogenesis. It seems that endometriotic mesenchymal stem cells (MSCs) show different characteristics compared to the normal MSCs. Determined high proliferation and low differentiation/ decidualization potential of endometriotic MSCs could be accompanied by their microRNAs deregulation influencing their fate and function. In this study for the first time, we evaluated the expression of miR-200b, miR-145, and let7b in endometriotic compared to non-endometriotic MSCs. These microRNAs are involved in biological pathways related to proliferation and differentiation of stem cells. Their aberrant expressions can disturb the proliferation/ differentiation balance in stem cells, altering their function and causing various diseases, like endometriosis. Materials and Methods In this experimental study, MSCs were isolated from three endometriotic and three non- endometriotic eutopic endometrium, followed by their characterization and culture. Expression of miR-200b, miR-145, and let-7b was ultimately analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results We found that the expression of miR-200b was up-regulated (P<0/0001) whereas the expression of miR- 145 and let-7b was down-regulated (P<0.0001) in endometriotic MSCs in comparison with non-endometriotic normal controls. ConclusionProliferation and differentiation are important dynamic balanced biological processes, while in equillibrium, they determine a healthy stem cell fate. It seems that they are deregulated in endometriotic MSCs and change their function. miR-200b, miR-145, and let7b are deregulated during endometriosis and they have pivotal roles in the modulating proliferation and differentiation of stem cells. We found up-regulation of miR-200b and down-regulation of miR-145 and let-7b in endometriotic MSCs. These changes can increase self-renewal and migration, while decreasing differentiation of endometriotic MSCs. Our achievements emphasize previous findings on the importance of proliferation/ differentiation balance in MSCs and clarify the role of microRNAs as main players in faulty endometriotic stem cells development.

Premature immunosenescence impairs immune surveillance allowing the endometriotic stemcell to migrate: The cytokine profile as a common denominator

While endometriosis, one of the most common reasons for infertility, remains a multifactorial condition and its exact cause highly speculative, there are data pointing to novel pathways of disease initiation which involve a stem cell and its ability to migrate and implant after it differentiates into an endometriotic stem cell. Thus, the mechanisms conferring immune surveillance, which would also normally expel the mesenchymal endometriotic cell, impairing its migration and implantation, appear to be negatively influenced by a state of endometriotic premature immunosenescence. This interplay between the two immunological mechanisms and endometriosis is influenced by a number of common factors having an active role in the host's protection process that inhibits harmful diseases and maintains cellular homeostasis. It appears more than coincidental that production/inhibition of IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-15, IL-18, TNF-α, VEGF, ICAM-1, and the number of Tolllike receptors is the same in ...

De materia medica versus codex alimentarius for the reinforcement of the gynecologic immune system: the case of endometriosis.

Since the first Pharmacopoeia under the title “De Materia Medica,” the importance of the utilization of plants and herbs has been an invaluable medicinal tool successfully employed for strengthening the immune system for combating a number of diseases in general, or assisting fertility and reproductive issues in particular. The beneficial use of herbal extracts, constituting the basis of modern medicines, is lately under the shadow of Codex Alimentarius that threatens, if not properly applied, serious immunity features rendering the host defenseless for intercepting harmful invaders, one of which is the mesenchymal endometriotic stem cell causing endometriosis.

Properties of the Mesenchymal Endometriotic Stem Cell in the Context of the Immune System and Analysis of its Role in Endometriosis

Recent studies of human mesenchymal stem cells (hMSCs) have revealed a number of properties that, if managed appropriately, may positively assist a large number of reparative or regenerative cellular processes. Their ability to produce factors and hormones coupled with their colony forming unit (CFU) potential renders these cells a valuable cellular bank for several therapies. The mesenchymal endometriotic stem cell (MESC) also exhibits part of these general properties but, in a paradoxical way, is implicated in the onset of endometriosis and thus infertility, a condition that torments millions of women worldwide. Although, there is no clear distinction about the regenerative or disease causing potential between a healthy and a non-physiological MESC, its postulated way of action leading to endometriosis involves its migration to and invasion of ectopic tissue. Such action may entail either the escapement of the MESC from the immunological function of surveillance or a regulatory-type masking, like a class-II negative state, that hides it from immunological interception. Since the acquired information on MESCs is sparse, this essay will briefly review papers and the small number of patents available in order to provide insight relevant to the understanding of this cell's contradictory behavior, whilst the immunological properties of MESCs will be used to formulate a potential theoretical basis on how to obstruct the initiation of endometriosis.

Properties of the Mesenchymal Endometriotic Stem Cell in the Context of the Immune System and Analysis of its Role in Endometriosis

Properties of the Mesenchymal Endometriotic Stem Cell in the Context of the Immune System and Analysis of its Role in Endometriosis

Can Incapacitation of the Mesenchymal Endometriotic Stem Cell via the Fortification of the Immune System Lead to the Eradication of Endometriosis?

This paper attempts to explain the immunologic nature of endometriosis from the stage of the endometriotic mesenchymal non-hematopoietic stem cell up to the inability of the immune system to intercept it for protecting the organism. Thus, the central dogma of this proposition is how to appropriately fortify the immune system using non-toxic and natural substances in order to render it fully functional and able to protect the organism. Therefore, the direct analogy of oncologic cases that share the same characteristics with endometriosis (metastasis and invasion, unrestrained growth, development of new blood vessels and decreased apoptosis) is given, including those which escape immune surveillance. The aim of this work is to gather, through an international collaboration, the inspirational ideas of most, if not all investigators interested in such a wide-scaled project to find ways to strengthen the immune system to fight against the migration and invasion of the endometriotic cell. It is obvious that, with the exception of the guidelines given herewith, all other suggestions to approach the specific problem are welcome in order to form powerful cohort centers that will work towards eradicating a disease which torments millions of women globally.

Premature Immunosenescence Impairs Immune Surveillance Allowing the Endometriotic Stem Cell to Migrate: The Cytokine Profile as a Common Denominator

While endometriosis, one of the most common reasons for infertility, remains a multifactorial condition and its exact cause highly speculative, there are data pointing to novel pathways of disease initiation which involve a stem cell and its ability to migrate and implant after it differentiates into an endometriotic stem cell. Thus, the mechanisms conferring immune surveillance, which would also normally expel the mesenchymal endometriotic cell, impairing its migration and implantation, appear to be negatively influenced by a state of endometriotic premature immunosenescence. This interplay between the two immunological mechanisms and endometriosis is influenced by a number of common factors having an active role in the host's protection process that inhibits harmful diseases and maintains cellular homeostasis. It appears more than coincidental that production/inhibition of IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-15, IL-18, TNF-α, VEGF, ICAM-1, and the number of Tolllike receptors is the same in immunosenescent states and in conditions with reduced immune surveillance, while the same variations are recorded in endometriotic patients. It is probable that these are common to all process signals, guide the endometriotic stem cell and dictate its fate according to the stochastic, transdifferentiation (plasticity) or deterministic model to become capable of migration and tissue invasion. It is currently unknown whether the pathway taken by the hemopoietic stem cell to become endometriotic represents a normal or aberrant route of development. This prompts research into its isolation and in vitro study of its behavior in order to reveal its potential function and role in endometriosis. (Journal of Endometriosis 2010; 2: 7–18)

Premature immunosenescence impairs the immune surveillance mechanism(s) allowing the endometriotic stem cell to migrate

Premature immunosenescence impairs the immune surveillance mechanism(s) allowing the endometriotic stem cell to migrate