Encapsulated VEGF121-PLA microparticles promote angiogenesis in human endometrium stromal cells

Abraham, Sunil; Sanjay, Geetha; Majiyd, Noushin Abdul; Amutha, C.

doi:10.1186/s43141-021-00118-1

Cited by 4 publications

(3 citation statements)

References 34 publications

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“…Specifically, hUC-PRP reduced endometrial fibrosis, increased endometrial area and gland density, and restored the functionality of the tissue by enhancing neovascularization, cell proliferation and activating regenerative molecular pathways (i.e. PI3K/Akt), which are involved in cell survival and decidualization ( Fabi et al , 2017 ) or re-epithelialization (by increasing VEGF gene expression) ( Abraham et al. , 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Human umbilical cord platelet-rich plasma to treat endometrial pathologies: methodology, composition and pre-clinical models

Rodríguez-Eguren¹,

Miguel-Gómez²,

Francés-Herrero

et al. 2022

Human Reproduction Open

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STUDY QUESTION Can human umbilical cord platelet-rich plasma (hUC-PRP) efficiently treat endometrial damage and restore fertility in a preclinical murine model? SUMMARY ANSWER Local application of hUC-PRP promotes tissue regeneration and fertility restoration in a murine model of Asherman syndrome and endometrial atrophy (AS/EA). WHAT IS KNOWN ALREADY AS/EA are well-described endometrial pathologies that cause infertility, however, there are currently no gold standard treatments available. Recent reports have described the successful use of human platelet-rich plasma (hPRP) in reproductive medicine, and its regenerative potential is further enhanced using hUC-PRP, due to the ample growth factors and reduced pro-inflammatory cytokines in the latter. STUDY DESIGN, SIZE, DURATION hUC-PRP (n = 3) was processed, characterized, and delivered locally to endometrial damage in a murine model (n = 50). The hUC-PRP was either used alone or loaded into a decellularized porcine endometrium-derived extracellular matrix (EndoECM) hydrogel; endometrial regeneration, fertility outcomes and immunocompatibility were evaluated two weeks following treatment administration. PARTICIPANTS/MATERIALS, SETTING, METHODS Umbilical cord blood was obtained from women in childbirth. Endometrial damage (mimicking AS/EA) was induced using ethanol in eight-week-old C57BL/6 mice, and treated with the most concentrated hUC-PRP sample four days later. Characterization of hUC-PRP and immunotolerance was carried out with multiplex technology, while uterine samples were analyzed by immunohistochemistry and quantitative PCR. The number of embryos and their morphology was determined visually. LARGE SCALE DATA N/A. MAIN RESULTS AND THE ROLE OF CHANCE Platelet density was enhanced three-fold in hUC-PRP compared to that in hUC blood (P < 0.05). hUC-PRP was enriched with growth factors related to tissue regeneration (i.e., hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF-BB), and epidermal growth factor (EGF)), which were released constantly (in vitro) when hUC-PRP was loaded into EndoECM. Both treatments (hUC-PRP alone and hUC-PRP with EndoECM) were immunotolerated and caused significantly regeneration of the damaged endometrium, evidenced by increased endometrial area, neoangiogenesis, cell proliferation and gland density and lower collagen deposition with respect to non-treated uterine horns (P < 0.05). Additionally, we detected augmented gene expression of Akt1, VEGF, and Ang, which are involved in regenerative and proliferation pathways. Finally, hUC-PRP treatment restored pregnancy rates in the mouse model. LIMITATIONS, REASONS FOR CAUTION This proof-of-concept pilot study was based on a murine model of endometrial damage and the use of EndoECM requires further validation prior to clinical implementation for women affected by AS/EA. WIDER IMPLICATIONS OF THE FINDINGS The local administration of hUC-PRP has high impact and is immunotolerated in a murine model of AS/EA, as has been reported in other tissues, making it a promising candidate for heterologous treatment of these endometrial pathologies. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Ministerio de Ciencia, Innovación y Universidades; Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital, Generalitat Valenciana; and Instituto de Salud Carlos III. The authors do not have any conflicts of interest to declare.

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Section: Discussionmentioning

confidence: 99%

Human umbilical cord platelet-rich plasma to treat endometrial pathologies: methodology, composition and pre-clinical models

Rodríguez-Eguren¹,

Miguel-Gómez²,

Francés-Herrero

et al. 2022

Human Reproduction Open

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“…In recent years, scientists have shown that VEGF acts via the PI3K/AKT signaling pathway to promote EPC mobilization[ 43 ]. Differential gene expression analysis showed that high levels of PI3K and AKT increased VEGF expression and induced angiogenesis in EPCs[ 44 , 45 ]. The P38-MAPK pathway was also associated with the differentiation and mobilization EPCs from the bone marrow, which is the main source[ 46 , 47 ].…”

Section: Epcs and Coronary Artery Diseasementioning

confidence: 99%

Endothelial progenitor cells and coronary artery disease: Current concepts and future research directions

Xiao¹,

Kuang²

2021

WJCC

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Vascular injury is a frequent pathology in coronary artery disease. To repair the vasculature, scientists have found that endothelial progenitor cells (EPCs) have excellent properties associated with angiogenesis. Over time, research on EPCs has made encouraging progress regardless of pathology or clinical technology. This review focuses on the origins and cell markers of EPCs, and the connection between EPCs and coronary artery disease. In addition, we summarized various studies of EPC-capturing stents and EPC infusion therapy, and aim to learn from past technology to predict the future.

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“…Морфологический субстрат нарушения васкуляризации -склероз сосудов эндометрия и снижение экспрессии васкулоэндотелиального фактора роста (VEGF), максимум которого должен регистрироваться в средней секреторной фазе менструального цикла [7]. Важнейшую роль в развитии ХЭ играет трансформирующий фактор роста (TGF-β), который служит гистологическим маркером фиброза в тканях и показывает тяжесть заболевания [8,9].…”

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Morphological features of the endometrium in patients with atrophic chronic endometritis and impaired hemodynamics

Gazizova

Yashchuk

Васильевич

et al. 2022

V.F.Snegirev Archives of Obstetrics and Gynecology

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BACKGROUND: Chronic endometritis is a clinical and morphological syndrome in which, due to persistent endometrial damage to the endometrium by an infectious agent, multiple secondary morphofunctional changes occur that impair cyclic transformation and receptivity of the uterine mucosa. AIM: This study aimed to reveal morphological features of the endometrium in patients with atrophic chronic endometritis and impaired hemodynamics in the endometrium. MATERIALS AND METHODS: The study involved 86 female patients divided into two groups. Group 1 comprised 44 patients with chronic endometritis and impaired endometrial hemodynamics. Group 2 included 42 patients with chronic endometritis without impaired microcirculation in the endometrium. The patients underwent endometrial pipelle biopsy for histological and immunohistochemical examination to determine the expression of VEGF, TGF- and CD138 during the proliferative phase of the menstrual cycle. RESULTS: Histological examination revealed vascular sclerosis, plasma cells, inflammatory infiltrates, stromal fibrosis, granulomas, and hemorrhagic foci in patients with atrophic chronic endometritis and impaired hemodynamics. CONCLUSIONS: While examining the morphological picture of atrophic chronic endometritis with impaired hemodynamics, the formation of scar tissue was noted resulting in impaired blood circulation, which leads to focal hemorrhages in the uterine mucosa. According to immunohistochemical analysis, patients with impaired endometrial hemodynamics showed a statistically significant decrease in VEGF and an increase in TGF- expression, which indicates the severity of fibrosis.

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Encapsulated VEGF121-PLA microparticles promote angiogenesis in human endometrium stromal cells

Cited by 4 publications

References 34 publications

Human umbilical cord platelet-rich plasma to treat endometrial pathologies: methodology, composition and pre-clinical models

Human umbilical cord platelet-rich plasma to treat endometrial pathologies: methodology, composition and pre-clinical models

Endothelial progenitor cells and coronary artery disease: Current concepts and future research directions

Morphological features of the endometrium in patients with atrophic chronic endometritis and impaired hemodynamics

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