Minimally invasive delivery of human umbilical cord-derived mesenchymal stem cells by an injectable hydrogel via Diels–Alder click reaction for the treatment of intrauterine adhesions

Acta Biomaterialia, Journal Year: 2024, Volume and Issue: 177, P. 77 - 90

Published: Feb. 6, 2024

Language: Английский

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The pathophysiological role of estrogens in the initial stages of pregnancy: molecular mechanisms and clinical implications for pregnancy outcome from the periconceptional period to end of the first trimester

Human Reproduction Update, Journal Year: 2023, Volume and Issue: 29(6), P. 699 - 720

Published: June 23, 2023

Abstract BACKGROUND Estrogens regulate disparate female physiological processes, thus ensuring reproduction. Altered estrogen levels and signaling have been associated with increased risks of pregnancy failure complications, including hypertensive disorders low birthweight babies. However, the role estrogens in periconceptional period early is still understudied. OBJECTIVE AND RATIONALE This review aims to summarize current evidence on maternal during first trimester pregnancies conceived naturally following ART. Detailed molecular mechanisms related clinical impacts are extensively described. SEARCH METHODS Data for this narrative were independently identified by seven researchers Pubmed Embase databases. The keywords selected: ‘estrogens’ OR ‘estrogen level(s)’ ‘serum estradiol’ ‘estradiol/estrogen concentration’, ‘early pregnancy’ ‘first ‘preconceptional period’ ‘ART’ ‘In Vitro Fertilization (IVF)’ ‘Embryo Transfer’ ‘Frozen Embryo ‘oocyte donation’ ‘egg ‘miscarriage’ ‘pregnancy outcome’ ‘endometrium’. OUTCOMES During (defined here as critical time window starting 1 month before conception), play a crucial endometrial receptivity, through activation paracrine/autocrine signaling. A derailed estrogenic milieu within seems be detrimental both natural ART-conceived pregnancies. Low non-conception cycles On other hand, excessive supraphysiologic concentrations at LH peak correlate lower live birth rates higher complications. In pregnancy, plays massive placentation mainly modulating angiogenic factor expression—and development an immune-tolerant uterine micro-environment remodeling function killer T-helper cells. Lower thought trigger abnormal pregnancies, whereas excess worsen outcomes. WIDER IMPLICATIONS Most available endorses relation between outcomes, further depicting optimal concentration range optimize success. how co-operate factors order maintain fine balance local tolerance towards developing fetus immune responses pathogens remains elusive. Further studies highly warranted, also aiming identify determinants response biomarkers personalized administration regimens

Language: Английский

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Global Literature Analysis of Organoid and Organ‐on‐Chip Research

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 13(21)

Published: July 22, 2023

Organoids and cells in organ-on-chip platforms replicate higher-level anatomical, physiological, or pathological states of tissues organs. These technologies are widely regarded by academia, the pharmacological industry regulators as key biomedical developments. To map advances this emerging field, a literature analysis 16,000 article metadata based on quality-controlled text-mining algorithm is performed. The covers titles, keywords, abstracts categorized academic publications preprint databases published after 2010. identifies tracks 149 107 organs organ substructures modeled organoids organ-on-chip, respectively, stem cell sources, well 130 diseases, 16 groups organisms other than human mouse which organoid/organ-on-chip technology applied. illustrates changing diversity focus research captures its geographical distribution. downloadable dataset provided robust framework for researchers to interrogate with their own questions.

Language: Английский

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Challenges in Clinical Diagnosis and Management of Chronic Endometritis

Diagnostics, Journal Year: 2022, Volume and Issue: 12(11), P. 2711 - 2711

Published: Nov. 5, 2022

Chronic endometritis (CE) is a local mucosal infectious and inflammatory disorder characterized by unusual filtration of CD138(+) endometrial stromal plasmacytes. CE attracting attention due to its potential association with infertility unknown etiology, repeated implantation failure, recurrent pregnancy loss, several maternal/neonatal complications. Due the variance in study design among researchers, universal diagnostic criteria remain be established for clinical diagnosis management CE. This review article aims summarize current knowledge provide insights into unsolved questions on establish guidelines disease from viewpoint human reproduction.

Language: Английский

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Development of polarity-reversed endometrial epithelial organoids

Reproduction, Journal Year: 2024, Volume and Issue: 167(3)

Published: Jan. 12, 2024

The uterine epithelium is composed of a single layer hormone responsive polarized epithelial cells that line the lumen and form tubular glands. Endometrial organoids (EEO) can be generated from epithelia recapitulate cell composition responses in vitro. As such, development EEO represents major advance for facilitating mechanistic studies However, limitation use cultured basement membrane extract other hydrogels inner location apical membrane, thereby hindering direct access to surface study interactions with embryo or infectious agents such as viruses bacteria. Here, straightforward strategy was developed successfully reverses polarity EEO. result an apical-out organoid preserves distinct apical-basolateral orientation remains ovarian steroid hormones. Our investigations highlight utility polarity-reversed E. coli blastocysts. This method generating lays foundation developing new vitro functional assays, particularly regarding embryos during pregnancy luminal constituents pathological diseased state.

Language: Английский

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Amorphous curcumin-based hydrogels to reduce the incidence of post-surgical intrauterine adhesions

Regenerative Biomaterials, Journal Year: 2024, Volume and Issue: 11

Published: Jan. 1, 2024

Abstract The incidence of intrauterine adhesions (IUA) has increased with the rising utilization surgery. postoperative physical barrier methods commonly used, such as balloons and other fillers, have limited effectiveness may even cause further damage to remaining endometrial tissue. Herein, we developed an injectable thermosensitive hydrogel using Pluronic F127/F68 pharmaceutical excipients curcumin a natural active molecule. effectively addresses solubility low bioavailability issues associated curcumin. In vitro, drug release assays revealed that amorphous promotes dissolution sustained vitro experiments reveal high biocompatibility its ability enhance vascular formation while inhibiting expression fibrotic factor TGF-β1. To assess preventing IUAs, in vivo were conducted IUA rats compared class III medical device, new-crosslinked hyaluronic acid (NCHA) gel. According study, is more effective than NCHA group improving regeneration endometrium, increasing blood supply endometrium reducing abnormal deposition fibrin, thus effectively. This study provides promising strategy for treating IUA.

Language: Английский

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New Potential Pharmacological Options for Endometriosis Associated Pain

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7068 - 7068

Published: June 27, 2024

Endometriosis is a chronic inflammatory disorder characterized by the abnormal growth of endometrial-like tissue outside uterine cavity, affecting 10-15% women reproductive age. Pain most common symptom. Treatment options include surgery, which has limited effectiveness and high recurrence rates, pharmacotherapy. Hormonal therapies, commonly used for symptom management, can have side effects contraceptive outcomes, contributing to infertility associated with endometriosis, pain lesions often reappearing after treatment cessation. Among its etiological factors, immunological dysregulation plays significant role, representing an interesting target developing new therapeutic strategies. This review critically analyzes recent studies provide updated synthesis ongoing research into potential pharmacotherapies focusing on lesion progression, relief, improving quality life. Immunotherapy, natural anti-inflammatory antioxidant compounds drug repurposing show promise in addressing limitations current treatments targeting potentially offering non-invasive solutions managing endometriosis. Promising results been obtained from vitro animal model studies, but clinical trials are still limited. More effort needed translate these findings practice effectively reduce disease alleviate symptoms preserve capacity, patients' overall wellbeing.

Language: Английский

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Intrauterine adhesion

Taiwanese Journal of Obstetrics and Gynecology, Journal Year: 2024, Volume and Issue: 63(3), P. 312 - 319

Published: May 1, 2024

Intrauterine adhesions (IUA) occurred in the reproductive-age women are a big economic and health problem, resulting severe impairment of social, psychological physical function female genital organs. IUA-related symptoms or signs varied greatly from free ambiguous (an incidental finding during intervention) to ceased menstruation loss fecundability. The underlying pathophysiology is not completely understood, but intrauterine damage with broken basal layers endometrium formatting scar tissues fibrosis subsequently causing partial complete occlusion uterine cavity may be well-accepted hypothesis. Previously, infection most common cause develop IUA, now, surgery critical contributing majority cases IUA. In current review, update information about etiology, epidemiology, pathophysiology, sequelae prevention IUA will renewed. We emphasize importance awareness primary should considered routine clinical practice if has been applied, based on uncertainty ideal treatment for established unpredictable outcomes after treatment. So far, evidence supports that hyaluronic acid with/without other strategy valuable effective method reduce formation re-formation as well achieve best fertility outcome.

Language: Английский

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Lactobacillus-Loaded Easily Injectable Hydrogel Promotes Endometrial Repair via Long-Term Retention and Microenvironment Modulation

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Regeneration of the injured endometrium, particularly functional layer, is crucial for prevention uterine infertility. At present, clinical treatment using sodium hyaluronate hydrogel injection limited by its relatively low fluidity, short-term retention, and insufficient bioactive ingredients, so it necessary to develop an advanced healing-promoting hydrogel. The modulation microenvironment Lactobacillus presents a component that can facilitate regeneration layer. Our study introduces multifunctional Lactobacillus-loaded poly(N-isopropylacrylamide)-grafted bacterial cellulose (BC-g-PN@L) designed with superior injectability in situ stability. 25 °C (room temperature), uniform distribution achieved pressure only 7.90 kPa. 37 (body BC-g-PN@L forms robust three-dimensional nanonetwork, providing space substance exchange channels maintain viability bioactivity. Enhanced hydrophobic isopropyl groups poly(N-isopropylacrylamide) side chains rigid substrates, exhibits prolonged retention properties cavity, persisting over 21 days. These attributes endow versatile pro-healing capacity rat model endometrial injury. promotes development injectable hydrogels both histological repair endometrium.

Language: Английский

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Enhanced myofibroblast differentiation of eMSCs in intrauterine adhesions

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 4, 2025

Intrauterine adhesions (IUA) is one of the most common gynecological diseases and main causes uterine infertility. Among proposed hypotheses on IUA development, reduced endometrial regeneration resulting from loss functional stem cells has been as key factor affecting prognosis. However, underlying mechanisms mostly remain unclear. Because eMSCs (endometrial mesenchymal stem/stromal cells) play a critical role in both supporting gland development also preparing environment for embryo implantation through decidualization, characteristics functions were compared between derived non-IUA patients, to uncover important roles mechanisms. Endometrium biopsies collected patients controls. The fibrosis features eMSC distributions investigated with IHC (immunohistochemistry). Then isolated their analyzed vitro. Our results indicate that scar tissues are characterized hyper-activation pro-fibrotic fibroblast myo-differentiation, along number eMSCs. controls show similar perspectives cell morphology, proliferation, colony formation, exosome secretion, positive ratio markers conventional MSC markers, tri-differentiation efficiency, ability suppressing lymphocyte aging, promoting vascular tube formation. have levels decidualization higher migration, invasion, myofibroblast differentiation. Further investigations TGF-β pathway, which major inducer differentiation, up-regulated responsible enhanced differentiation potential IUA. In conclusion, we demonstrated here biopsy myofibroblast. tissues, capability increased.

Language: Английский

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