CD34+KLF4+ Stromal Stem Cells Contribute to Endometrial Regeneration and Repair

Yin, Mingzhu; Zhou, Huanjiao Jenny; Lin, Caixia; Long, Lingli; Yang, Xiaolei; Zhang, Haifeng; Taylor, Hugh S.; Wang, Min

doi:10.1016/j.celrep.2019.04.088

Cited by 64 publications

(67 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, CD34 + KLF + endometrial stromal stem/progenitor cells were identified in the perivascular region in the endometrium of a menstruating mouse model ( Yin et al, 2019 ). They expressed the smooth muscle marker, SM22α, and vimentin and upon estrogen stimulation trans-differentiated into gland-like structures lined with E-cadherin-expressing epithelial cells.…”

Section: Human Endometrial Mscmentioning

confidence: 99%

Endometrial and Menstrual Blood Mesenchymal Stem/Stromal Cells: Biological Properties and Clinical Application

Bozorgmehr

Gurung

Darzi

et al. 2020

Front. Cell Dev. Biol.

147

116

View full text Add to dashboard Cite

show abstract

Section: Human Endometrial Mscmentioning

confidence: 99%

Endometrial and Menstrual Blood Mesenchymal Stem/Stromal Cells: Biological Properties and Clinical Application

Bozorgmehr

Gurung

Darzi

et al. 2020

Front. Cell Dev. Biol.

147

116

View full text Add to dashboard Cite

show abstract

“…Moreover, CD34 is a transmembrane phosphoglycoprotein and well-studied marker for hematopoietic stem and progenitor cells. Recently, it has been suggested that CD34 is expressed by vascular endothelial progenitors and endometrial stromal stem cells particularly displaying neovascular formation [26,52]. Immuno uorescence staining of CD31 ( Fig.…”

Section: Intra-uterine Cxcl12 Treatment Promotes Uterine Angiogenesismentioning

confidence: 95%

“…Various substances including granulocyte colony-stimulating factor (G-CSF), mesenchymal stem cells (MSC), and platelet-rich plasma (PRP) have been suggested to enhance endometrial angiogenesis and receptivity for patients who are suffering from implantation failure with poor endometrial receptivity [22][23][24]. However, the e cacy of those substances still has not been fully evidenced yet [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Embryo-Derived Chemokine CXCL12 Enhances Pregnancy Outcome via Improvement of Endometrial Receptivity

Koo

Yoon

Hong

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Successful pregnancy inevitably depends on the implantation of a competent embryo into a receptive endometrium. Although a remarkable improvement of assisted reproductive technology (ART) has been achieved over the last few decades, there are still a number of infertile women experiencing frequent ART failure after repeated attempts due to many unsolved problems including repeated failure of implantation. Many substances have been suggested to improve the rates of embryo implantation by enhancing the endometrial receptivity for the patients who are suffering from repeated failure of implantation. However, despite these numerous extensive research work, there are currently no effective evidence-based treatments to prevent or cure this condition. Therefore, here we aim to suggest non-invasive intra-uterine administration of embryo-secreted chemokine CXCL12 as an effective therapeutic intervention to solve this problem.Results: We demonstrated that chemokine CXCL12 is derived from pre- and peri-implanting embryos and its interaction with endometrial CXCR4 and CXCR7 enhances endometrial receptivity and significantly promoted endothelial vessel formation and sprouting in vitro. Consistently, intra-uterine CXCL12 administration in vivo, which is a completely non-invasive treatment strategy, improved endometrial receptivity showing increased integrin b3 and its ligand osteopontin, and induced endometrial angiogenesis displaying increased numbers of vessel formation near the lining of endometrial epithelial layer with higher CD31 and CD34 expression. Furthermore, intra-uterine CXCL12 application dramatically promoted the rates of embryo implantation with no morphologically retarded embryos. Conclusions: Our present study provides a novel evidence that improved uterine endometrial receptivity and enhanced angiogenesis induced by embryo-derived chemokine CXCL12 may aid to develop a non-invasive therapeutic strategy for clinical treatment or supplement for the patients with repeated implantation failure with less risk.

show abstract

“…Although the physiological and pathological changes in the endometrium during remodeling are well characterized, the cellular mechanisms that drive the programmed events of the endometrial tissue remodeling are still not completely understood. Recent studies provide evidence for endometrial stem cell (ESC) populations that contribute to endometrial regeneration and repair [14,15]. However, these studies have either used rodent models that does not experience menstrual shedding or artificial mouse models with administration and withdrawal of exogenous progesterone rather than the naturally menstruating women with declining hormone levels caused by the demise of corpus luteum.…”

Section: Introductionmentioning

confidence: 99%

Development of A 3D Tissue Slice Culture Model for the Study of Human Endometrial Repair and Regeneration

et al. 2020

View full text Add to dashboard Cite

The human endometrium undergoes sequential phases of shedding of the upper functionalis zone during menstruation, followed by regeneration of the functionalis zone from the remaining basalis zone cells, and secretory differentiation under the influence of the ovarian steroid hormones estradiol (E2) and progesterone (P4). This massive tissue regeneration after menstruation is believed to arise from endometrial stromal and epithelial stem cells residing in the basal layer of the endometrium. Although many endometrial pathologies are thought to be associated with defects in these stem cells, studies on their identification and regulation are limited, primarily due to lack of easily accessible animal models, as these processes are unique to primates. Here we describe a robust new method to study endometrial regeneration and differentiation processes using human endometrial tissue slice cultures incorporating an air-liquid interface into a 3D matrix scaffold of type I collagen gel, allowing sustained tissue viability over three weeks. The 3D collagen gel-embedded endometrial tissue slices in a double-dish culture system responded to ovarian steroid hormones, mimicking the endometrial changes that occur in vivo during the menstrual cycle. These changes included the E2-induced upregulation of Ki-67, estrogen receptor (ER), and progesterone receptor (PR) in all endometrial compartments and were markedly suppressed by both P4 and E2 plus P4 treatments. There were also distinct changes in endometrial morphology after E2 and P4 treatments, including subnuclear vacuolation and luminal secretions in glands as well as decidualization of stromal cells, typical characteristics of a progestational endometrium in vivo. This long-term slice culture method provides a unique in vivo-like microenvironment for the study of human endometrial functions and remodeling during early pregnancy and experiments on stem cell populations involved in endometrial regeneration and remodeling. Furthermore, this model has the potential to enable studies on several endometrial diseases, including endometrial cancers and pregnancy complications associated with defects in endometrial remodeling.

show abstract

CD34+KLF4+ Stromal Stem Cells Contribute to Endometrial Regeneration and Repair

Cited by 64 publications

References 84 publications

Endometrial and Menstrual Blood Mesenchymal Stem/Stromal Cells: Biological Properties and Clinical Application

Endometrial and Menstrual Blood Mesenchymal Stem/Stromal Cells: Biological Properties and Clinical Application

Embryo-Derived Chemokine CXCL12 Enhances Pregnancy Outcome via Improvement of Endometrial Receptivity

Development of A 3D Tissue Slice Culture Model for the Study of Human Endometrial Repair and Regeneration

Contact Info

Product

Resources

About