CXCL12 Promotes Stem Cell Recruitment and Uterine Repair after Injury in Asherman’s Syndrome

Ersoy, Gülçı̇n Şahin; Zolbin, Masoumeh Majidi; Çoşar, Emine; Moridi, Irene; Mamillapalli, Ramanaiah; Taylor, Hugh S.

doi:10.1016/j.omtm.2017.01.001

Cited by 61 publications

(52 citation statements)

References 36 publications

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“…The disappearance of normal endometrium structure changes the functionality of this organ . Loss of native stem cells or injury of stem cells niche caused by iatrogenic curettage often leads to failed regeneration of the functional layer of endometrium and results in amenorrhea, infertility, or pregnancy complications …”

Section: Discussionmentioning

confidence: 97%

PGS Scaffolds Promote the In Vivo Survival and Directional Differentiation of Bone Marrow Mesenchymal Stem Cells Restoring the Morphology and Function of Wounded Rat Uterus

Xiao

Yang

Lei

et al. 2019

Adv Healthcare Materials

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Intrauterine adhesion (IUA) causing infertility and recurrent miscarriage of reproductive female mammals usually results from endometrium injury. Nevertheless, there is no efficient therapeutic method to avoid IUA. Bone marrow derived mesenchymal stem cells (BMSCs) are an important cell source for tissue regeneration. This study designs and explores the ability of BMSC‐loaded elastic poly(glycerol sebacate) (PGS) scaffold to prevent IUA and compares the effect of PGS with poly(lactic‐co‐glycolic acid) (PLGA) and collagen scaffolds in resumption of damaged rat uteruses. The 3D architecture provided by PGS scaffolds favors the attachment and growth of rat BMSCs. In vivo bioluminescence imaging shows that compared with direct BMSC intrauterine injection, PLGA, and collagen scaffolds, the PGS scaffold significantly prolongs the retention time of BMSCs in a wounded rat uterus model. More importantly, BMSCs can directly differentiate into endometrial stromal cells after transplantation of PGS/BMSCs constructs, but not PLGA/BMSCs and collagen/BMSCs. It is found that the level of transforming growth factor β1 (TGF‐β1), basic fibroblast growth factor (bFGF), vascular endothelial growth factor, and insulin‐like growth factors in the injured endometrium adjacent to PGS/BMSCs constructs is higher than those of rats receiving PLGA/BMSCs, collagen/BMSCs, or BMSCs intrauterine transplantation. Besides, transplantation of PGS/BMSCs leads to better morphology recovery of the damaged uterus than PLGA/BMSCs and collagen/BMSCs. The receptive fertility of PGS/BMSCs is 72.2 ± 6.4%, similar to the one of collagen/BMSCs, but significantly higher than 42.3 ± 3.9% in PLGA/BMSCs. Taken together, PGS/BMSCs may be a promising candidate for preventing IUA.

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Section: Discussionmentioning

confidence: 97%

PGS Scaffolds Promote the In Vivo Survival and Directional Differentiation of Bone Marrow Mesenchymal Stem Cells Restoring the Morphology and Function of Wounded Rat Uterus

Xiao

Yang

Lei

et al. 2019

Adv Healthcare Materials

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“…Asherman's syndrome is an acquired condition of uterine fibrosis and adhesions in response to injury. 54 Specifically, following uterine injury to create a model of AS, it was demonstrated that CXCL12 augmentation increased BMDSC engraftment and that the CXCL12 receptor (CXCR4) antagonist, ADM3100 (Plerixafor which is FDA approved), blocked stem cell recruitment. 41,49-51 While the generation and growth of the uterine endometrium are important physiologically for reproduction, it is defective in AS.…”

Section: Xcl12 S I G Naling In a S Herman ' S Syndromementioning

confidence: 99%

“…49,53 Aside from surgery, which is not fully effective, no therapies are currently available to treat this disease. 54 Unlike the case for endometriosis in which the CXCL12/ CXCR4/CXCR7 axis plays a key role in promoting disease, the interaction of CXCL12 with CXCR4 on murine models of AS has shown a decrease in fibrosis and improved fertility. Sites of injury are known to increase expression of CXCL12; however, CXCL12 is rapidly proteolyzed and does not mobilize cells for a prolonged duration.…”

Section: Xcl12 S I G Naling In a S Herman ' S Syndromementioning

confidence: 99%

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The CXL12/CXCR4/CXCR7 axis in female reproductive tract disease: Review

Krikun

2018

American J Rep Immunol

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Initial studies on the chemokine stromal derived factor 1 (now referred to as CXCL12) were proposed to be enhanced in several diseases including those which affect the female reproductive tract. These include endometriosis, Asherman's syndrome, endometrial cancers, and ovarian cancers. Additionally, recent studies from our laboratory suggest that CXCL12 signaling is involved in leiomyomas (fibroids). These diseases present an inflammatory/hypoxic environment which further promotes pathology. At first, studies focused on signaling by CXCL12 via its well-known receptor, CXCR4. However, the discovery of CXCR7 as another receptor for CXCL12 with rather high binding affinity and recent reports about its involvement in endometrial disease and cancer progression has questioned the potential of "selective blockade"' of CXCR4 to treat these ailments. This review will focus on the signaling and effects of the potent chemokine CXCL12, and its long-known G protein-coupled receptor CXCR4, as well as the alternate receptor CXCR7 on the female reproductive tract and related diseases such as endometriosis, Asherman's syndrome, leiomyomas, endometrial cancer, and ovarian cancer. Although several other mechanisms are inherent to these diseases such as gene mutations, differential expression of miRNAs and epigenetics, for this review, we will focus on the CXCL12/CXCR4/CXCR7 axis as a novel target.

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“…The most common early symptoms of IUA patients are menstrual abnormalities, recurrent abdominal pain, and amenorrhea [4]. IUA often leads to infertility, recurrent miscarriage, and various complications of pregnancy, such as placenta implantation, placental abruption, preterm premature rupture of membranes, and developmental abnormalities in the fetus as a result of the loss of normal endometrium and insu cient the blood supply to the uterus [5][6][7]. In recent years, IUA has become one of the common causes of female infertility in China, and its incidence has been on the rise with uterine cavity surgery increasing [4,8].…”

Section: Introductionmentioning

confidence: 99%

Decreased CXCL5 expression associated with intrauterine adhesions in a rat model and human endometrial tissues

Sun

Fang

Gao

et al. 2020

Preprint

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Background Intrauterine adhesion (IUA) is a consequence of endometrium damage, leading to infertility, recurrent miscarriage, and various complications of pregnancy. IUA usually occurs after an infection or injury-related inflammation of the endometrium. CXCL5, a member of chemokines, is associated with the remodeling of connective tissues, but its roles in the formation of IUA remain uncertain. This study aims to investigate the expression and effect of CXCL5 in the development of IUA. Results CXCL5 protein level in the endometrium of IUA rat is significantly decreased compared with that in normal and sham-operated endometria of rats (P < 0.001). Furthermore, real-time PCR and western blotting assays also show that the CXCL5 expression in endometrial tissues from IUA patients is much lower than that in normal endometrium (P < 0.01), which is consistent with the results based on the rat model. CXCL5 significantly up-regulates MMP9 expression and slightly up-regulates p65 expression in human endometrial cells after CXCL5 overexpression. Conclusions These results show that CXCL5 plays an important role in the inhibition of IUA formation after injury by modulating MMP9 expression and therefore has a protective effect of CXCL5 in the adhesion formation of IUA. These findings provide valuable information for evaluating prognosis and guiding therapy of intrauterine adhesions.

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CXCL12 Promotes Stem Cell Recruitment and Uterine Repair after Injury in Asherman’s Syndrome

Cited by 61 publications

References 36 publications

PGS Scaffolds Promote the In Vivo Survival and Directional Differentiation of Bone Marrow Mesenchymal Stem Cells Restoring the Morphology and Function of Wounded Rat Uterus

PGS Scaffolds Promote the In Vivo Survival and Directional Differentiation of Bone Marrow Mesenchymal Stem Cells Restoring the Morphology and Function of Wounded Rat Uterus

The CXL12/CXCR4/CXCR7 axis in female reproductive tract disease: Review

Decreased CXCL5 expression associated with intrauterine adhesions in a rat model and human endometrial tissues

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