Adipose-derived stem cells transplantation improves endometrial injury repair

Shao, Xiaowen; Ai, Guihai; Wang, Lian; Qin, Jinlong; Li, Yue; Jiang, Huici; Zhang, Tingting; Zhou, Linlin; Gao, Zhengliang; Cheng, Jiajing; Cheng, Zhongping

doi:10.1017/s096719941900042x

Cited by 46 publications

(33 citation statements)

References 38 publications

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“…ADSCs have significant effects on the repair of premature ovarian failure (Xie et al, 2017), repair of myocardial injury (Lee et al, 2020), repair of nerve injury (Sadie-Van Gijsen, 2019), regeneration of bone and cartilage (Tiscornia et al, 2006), liver (Liu and Chen, 2018), and kidney (Zuk et al, 2002) after injury. Our previous studies also found that ADSCs transplantation can improve the repair of endometrial injury (Shao et al, 2019). Exosomes are nanoscale vesicles, approximately 30-100 nm in diameter, released into the extracellular environment in the form of exocytosis after fusion of intracellular Multivesicular Bodies (MVBs) with the cell membrane (Xie and Zeng, 2020).…”

Section: Discussionmentioning

confidence: 99%

ADSC Exosomes Mediate lncRNA-MIAT Alleviation of Endometrial Fibrosis by Regulating miR-150-5p

Shao

Qin

Wan³

et al. 2021

Front. Genet.

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BackgroundSecondary infertility remains a major complication of endometrial fibrosis in women. The use of exosomes from adipose-derived mesenchymal stem cells (ADSCs) has shown promising results for the treatment of endometrial fibrosis. However, the mechanisms of action of ADSC-exosome (ADSC-Exo) therapy remain unclear.Materials and MethodsAn endometrial fibrosis model was established in mice treated with alcohol and endometrial epithelial cells (ESCs) treated with TGF-β1. ADSCs were isolated from Sprague Dawley (SD) rats, and exosomes were isolated from ADSCs using ExoQuick reagent. Exosomes were identified by transmission electron microscopy (TEM), NanoSight, and Western blot analysis. The expression level of lncRNA-MIAT was detected by qPCR analysis. Western blot analysis was carried out to determine the protein levels of fibrosis markers (TGFβR1, α-SMA, and CK19). A dual-luciferase reporter gene assay was used to verify the relationship between target genes. The endometrial tissues of the endometrial fibrosis model were stained with HE and Masson’s trichrome.ResultsADSCs and ADSC-Exos were successfully isolated, and the expression level of lncRNA-MIAT was significantly down-regulated in endometrial tissue and the TGF-β1-induced ESC injury model, whereas ADSC-Exos increased the expression of lncRNA-MIAT in the TGF-β1-induced ESC model. Functionally, ADSC-Exo treatment repressed endometrial fibrosis in vivo and in vitro by decreasing the expression of hepatic fibrosis markers (α-SMA and TGFβR1) and increasing the expression of CK19. Moreover, miR-150-5p expression was repressed by lncRNA-MIAT in the TGF-β1-induced ESC injury model. The miR-150-5p mimic promoted TGF-β1-induced ESC fibrosis.ConclusionADSC-Exos mediate lncRNA-MIAT alleviation of endometrial fibrosis by regulating miR-150-5p, which suggests that lncRNA-MIAT from ADSC-Exos may be a viable treatment for endometrial fibrosis.

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Section: Discussionmentioning

confidence: 99%

ADSC Exosomes Mediate lncRNA-MIAT Alleviation of Endometrial Fibrosis by Regulating miR-150-5p

Shao

Qin

Wan³

et al. 2021

Front. Genet.

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“…The regeneration and repair of endometrium depend on the proliferation and differentiation of the basal layer stem cells [28] , and the development of IUA is related to stem cell exhaust or loss function. Recently, much attention has been paid to stem cell therapy in endometrial repair [29][30][31] . The possible mechanisms of stem cells repairing damaged intima include homing, induction, paracrine and immunoregulation [20,32,33] .…”

Section: Discussionmentioning

confidence: 99%

A Combination of Bone Marrow Mesenchymal Stem Cells with Estrogen Improves Rabbit Endometrial Injury Repair by a Mechanism Involved in an Activation of Wnt/β-catenin Signaling

Lei

Cao

et al. 2021

Preprint

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Background: Although the effect of bone marrow mesenchymal stem cells (BMSCs) combined with estrogen therapy in the repair of endometrial injury has been confirmed, its underlying molecular mechanism in intrauterine adhesion (IUA) remains unclear. In this study, we aim to investigate the effect and involvement of a combination of BMSCs with estrogen in restoration of injured endometrium by applying a rabbit endometrial injury model. Method: BMSCs were isolated and labeled with PKH26 fluorescent dye. The IUA animal model was generated by a dual damage method of mechanical curettage and lipopolysaccharide infection. Rabbits were randomly assigned to the following 5 groups: sham operation group, IUA model group, E2 treatment group, BMSCs treatment group, and BMSCs combined with E2 treatment group. Bilateral uterus were obtained at different time points for the further study. HE and Masson staining were used to evaluate the number of endometrial glands and the degree of fibrosis. The expression of fibrosis and EMT related markers were observed by Immunohistochemical, immunofluorescence staining and Western blot. The expression of core molecules in the Wnt/β-catenin signaling pathway was examined by Western blot.Results: In the present study, it is found that PKH26 fluorescent dye can successfully label BMSCs and track the distribution and differentiation of transplanted BMSCs. BMSCs differentiated into endometrial epithelial cells and mainly located around the endometrial glands and extracellular matrix at 3 or 5 days post-transplantation, while BMSCs primarily differentiated into endometrial stromal cells at 7 days after orthotopic transplantation. Furthermore, after combined treatment of BMSCs and estrogen, the number of glands increased significantly, and the area of fibrosis reduced evidently, accompanied by a downregulation of mesenchymal markers and upregulation of epithelial markers when compared with each single treatment group. The expression levels of core molecules in the Wnt/β-catenin signaling pathway were higher in the BMSCs+E2 group than in the other treatment groups. Conclusions: Our study demonstrates that BMSCs combined with estrogen can improve the repair after endometrial injury by promoting the proliferation of endometrial epithelial cells and inhibiting EMT and endometrial fibrosis. This combined effect is achieved in part through activation of the Wnt/β-catenin signaling pathway.

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“…There are relatively few studies on AD‐MSCs in endometrial repair. AD‐MSCs and their exosomes promote regeneration of the endometrium in rats with intrauterine adhesion, improve endometrial receptivity, and reshape endometrium fertility (Shao et al, 2019 ; Zhao et al, 2020 ), which indicates the local application of AD‐MSC exosomes in the uterus may be a promising treatment for patients with intrauterine adhesion. Other studies have shown that conditioned medium from endometrial cancer cell‐pretreated adipose‐derived stem cells (ADSCs) promotes endometrial cancer cell proliferation and migration by activating the STAT3 signaling pathway (Chu et al, 2018 ), which suggests that ADSCs are context‐dependent by the tumor milieu.…”

Section: Progress and Challenges Of Endometrial Repair By Adult Stem Cellsmentioning

confidence: 99%

Adult stem cells in endometrial regeneration: Molecular insights and clinical applications

Wang

Luo

et al. 2021

Molecular Reproduction Devel

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Endometrial damage is an important cause of female reproductive problems, manifested as menstrual abnormalities, infertility, recurrent pregnancy loss, and other complications. These conditions are collectively termed “Asherman syndrome” (AS) and are typically associated with recurrent induced pregnancy terminations, repeated diagnostic curettage and intrauterine infections. Cancer treatment also has unexpected detrimental side effects on endometrial function in survivors independently of ovarian effects. Endometrial stem cells act in the regeneration of the endometrium and in repair through direct differentiation or paracrine effects. Nonendometrial adult stem cells, such as bone marrow‐derived mesenchymal stem cells and umbilical cord‐derived mesenchymal stem cells, with autologous and allogenic applications, can also repair injured endometrial tissue in animal models of AS and in human studies. However, there remains a lack of research on the repair of the damaged endometrium after the reversal of tumors, especially endometrial cancers. Here, we review the biological mechanisms of endometrial regeneration, and research progress and challenges for adult stem cell therapy for damaged endometrium, and discuss the potential applications of their use for endometrial repair after cancer remission, especially in endometrial cancers. Successful application of such cells will improve reproductive parameters in patients with AS or cancer. Significance: The endometrium is the fertile ground for embryos, but damage to the endometrium will greatly impair female fertility. Adult stem cells combined with tissue engineering scaffold materials or not have made great progress in repairing the injured endometrium due to benign lesions. However, due to the lack of research on the repair of the damaged endometrium caused by malignant tumors or tumor therapies, the safety and effectiveness of such stem cell‐based therapies need to be further explored. This review focuses on the molecular insights and clinical application potential of adult stem cells in endometrial regeneration and discusses the possible challenges or difficulties that need to be overcome in stem cell‐based therapies for tumor survivors. The development of adult stem cell‐related new programs will help repair damaged endometrium safely and effectively and meet fertility needs in tumor survivors.

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Adipose-derived stem cells transplantation improves endometrial injury repair

Cited by 46 publications

References 38 publications

ADSC Exosomes Mediate lncRNA-MIAT Alleviation of Endometrial Fibrosis by Regulating miR-150-5p

ADSC Exosomes Mediate lncRNA-MIAT Alleviation of Endometrial Fibrosis by Regulating miR-150-5p

A Combination of Bone Marrow Mesenchymal Stem Cells with Estrogen Improves Rabbit Endometrial Injury Repair by a Mechanism Involved in an Activation of Wnt/β-catenin Signaling

Adult stem cells in endometrial regeneration: Molecular insights and clinical applications

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