Therapeutic options and drug delivery strategies for the prevention of intrauterine adhesions

Kou, Longfa; Jiang, Xue; Xiao, Shuyi; Zhao, Ying‐Zheng; Yao, Qing; Chen, Ruijie

doi:10.1016/j.jconrel.2019.12.007

Cited by 109 publications

(74 citation statements)

References 105 publications

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“…Second is the angiogenesis disorder. The formation of IUAs, to a great extent, is related to intrauterine operation [30]. Once the intrauterine operation is damaged to the basal layer, or even to the muscular layer, the state of ischemia and hypoxia hinders the proliferation of epithelial and interstitial cells, resulting in the obstruction of new angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Quantification of the CM-Dil-labeled human umbilical cord mesenchymal stem cells migrated to the dual injured uterus in SD rat

et al. 2020

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Background: Human umbilical cord mesenchymal stem cell (hUC-MSC) therapy is considered as a promising approach in the treatment of intrauterine adhesions (IUAs). Considerable researches have already detected hUC-MSCs by diverse methods. This paper aims at exploring the quantitative distribution of CM-Dil-labeled hUC-MSCs in different regions of the uterus tissue of the dual injury-induced IUAs in rats and the underlying mechanism of restoration of fertility after implantation of hUC-MSCs in the IUA model. Methods: In this study, we investigated the quantification of the CM-Dil-labeled hUC-MSCs migrated to the dual injured uterus in Sprague Dawley rats. Additionally, we investigated the differentiation of CM-Dil-labeled hUC-MSCs. The differentiation potential of epithelial cells, vascular endothelial cells, and estrogen receptor (ER) cells were assessed by an immunofluorescence method using CK7, CD31, and ERα. The therapeutic impact of hUC-MSCs in the IUA model was assessed by hematoxylin and eosin, Masson, immunohistochemistry staining, and reproductive function test. Finally, the expression of TGF-β1/Smad3 pathway in uterine tissues was determined by qRT-PCR and Western blotting. Results: The CM-Dil-labeled cells in the stroma region were significantly higher than those in the superficial myometrium (SM) (71.67 ± 7.98 vs. 60.92 ± 3.96, p = 0.005), in the seroma (71.67 ± 7.98 vs. 23.67 ± 8.08, p = 0.000) and in the epithelium (71.67 ± 7.98 vs. 4.17 ± 1.19, p = 0.000). From the 2nd week of treatment, hUC-MSCs began to differentiate into epithelial cells, vascular endothelial cells, and ER cells. The therapeutic group treated with hUC-MSCs exhibited a significant decrease in fibrosis (TGF-β1/Smad3) as well as a significant increase in vascularization (CD31) compared with the untreated rats.

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Section: Discussionmentioning

confidence: 99%

Quantification of the CM-Dil-labeled human umbilical cord mesenchymal stem cells migrated to the dual injured uterus in SD rat

et al. 2020

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“…Stem cell and brosis were highly concentrated in the 2010s. In recent years, researchers have paid more and more attention to the effectiveness of adjuvant therapy after hysteroscopic adhesiolysis in suppressing reformation of adhesion and promoting endometrial regeneration (57). Previous researches focused on placement of uterine stents, foley catheters, hyaluronic acid or hormone replacement therapy (58).…”

Section: Discussionmentioning

confidence: 99%

The Top 100 Most Cited Articles on Intrauterine Adhesion: A Bibliometric Analysis

2021

Preprint

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Background: Bibliometric analysis is a statistical method which attempts to assess articles by their citations, analyzing their frequency and pattern of citing phenomenon. Through the analysis, some guidance can be extracted for future research directions. Over the past few years, there have been articles published in mounting numbers focused on intrauterine adhesions. Nevertheless, little is known about the properties and qualities of these researches. No existed analysis commits to reflecting the progress of researches in intrauterine adhesion.Methods: Web of Science Core Collection, BIOSIS Citation Index and MEDLINE were searched for the identifying articles released from 1950 to October 2020. Articles concerning about Intrauterine adhesion were determined. Subsequently, the 100 most cited articles were chosen for analysis of citation count, citation density (citations/article age), authorship, theme, geographic distribution, time-related flux, level of evidence, and network analysis.Results: An overwhelming majority of the certain 100 articles were put out in the 2010s (35%). Citations per article ranged from 30 to 253. China possesses the most papers among the top 100 papers, followed by the USA, France, Israel and Italy. The study theme that most highlighted were operative hysteroscopy and adjunctive treatments for improving reproductive outcome. Level II is the most common level of evidence, and there is no statistical difference in the number of citations between the levels. The network analysis connoted that hysteroscopy, hysteroscopic adhesiolysis, infertility, and reproductive outcome had a great degree of centrality in the 2000s and 2010s, while placental implantation had a great degree of centrality in the 2000s and stem cell and fibrosis had a great degree of centrality in the 2010s. Conclusions: We conducted a bibliometric analysis of the top 100 most cited articles in the literature on intrauterine adhesions. It is worth noting that hysteroscopy and hysteroscopic adhesiolysis were long-term concern in the field of intrauterine adhesion researches. As the elapse of time, postoperative adjuvant treatment has gradually become the hot spot of researches. However, there are only 9 experimental articles among these 100 articles, showing the lack of breakthrough progress in the field of intrauterine adhesions at the mechanism level.

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“…These disorders are characterized by low pregnancy rates, frequent miscarriages, and even infertility [1][2][3]. Currently, intrauterine implant positioning and high-dose hormone therapy are used in tandem to avoid postoperative recurrence of IUAs and facilitate endometrial repair and regeneration [4,5]. However, the conventional hormone replacement therapy for endometrium injury generally causes adverse side effects.…”

Section: Introductionmentioning

confidence: 99%

Exosomes Derived from Umbilical Cord Mesenchymal Stem Cells Activate PTEN/AKT Pathway and Promote Repair of Damaged Endometrium

Wang

Liu

et al. 2021

Preprint

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BackgroundEndometrial injury contributes to impaired endometrial receptivity, and is well recognized as a critical factor in implantation failure. Increasing evidence suggests that the therapeutic effects of mesenchymal stem cells (MSCs) mainly depend on their capacity to secrete paracrine factors and are mediated by MSC-derived exosomes (MSC-Exos). In this study, we aimed to explore the effects of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) on injured endometrium in the mouse endometrial damage model and the potential mechanisms for these effects.MethodsAll female mice were randomly divided into control group, saline group, and exosome group. To observe the distribution of exosomes in vivo, DiR-labeled hUCMSC-Exos were injected into the tail vein of endometrium-injured mice. HE staining was used to detect changes in endometrial thickness and number of glands. TUNEL staining was used to detect cells apoptosis. The expression of Ki67 and CD31 was examined by immunohistochemistry. Then, western blotting was used to measure the expression of Bcl-2, Bax, Cleaved Caspase-3, PTEN, AKT and p-AKT. The expression of VEGF and IGF-1 was detected by RT-PCR.ResultshUCMSC-Exos was able to migrate to the damaged endometrium. After hUCMSC-Exos injection, the endometrial thickness and the number of glands were significantly increased (P< 0.05). Compared with the saline group, apoptosis was significantly reduced in the exosome group, and the expression of Ki67 and CD31 was significantly increased (P< 0.05). Besides, the expression of Bax, Cleaved Caspase-3 and PTEN was reduced as hUCMSC-Exos addition, and the Bcl-2 and p-Akt expression was increased. The expression of VEGF and IGF-1 was significantly upregulated in the exosome group compared to the saline group (P< 0.05).ConclusionshUCMSC-Exos ameliorated the damaged uterus, increased endometrial thickness, suppressed apoptosis and improved the cell proliferation in the mouse injured endometrium model. Furthermore, we discovered that hUCMSC-Exos could activate the PTEN/AKT signaling pathways and induce the overexpression of VEGF and IGF-1 in vivo.

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Therapeutic options and drug delivery strategies for the prevention of intrauterine adhesions

Cited by 109 publications

References 105 publications

Quantification of the CM-Dil-labeled human umbilical cord mesenchymal stem cells migrated to the dual injured uterus in SD rat

Quantification of the CM-Dil-labeled human umbilical cord mesenchymal stem cells migrated to the dual injured uterus in SD rat

The Top 100 Most Cited Articles on Intrauterine Adhesion: A Bibliometric Analysis

Exosomes Derived from Umbilical Cord Mesenchymal Stem Cells Activate PTEN/AKT Pathway and Promote Repair of Damaged Endometrium

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