Placental extracellular vesicles induce ovarian tumour cell death in an ex vivo explant model: Possible therapeutic potential.

Introduction: Placental extracellular vesicles (EVs), lipid-enclosed particles released from the placenta, can facilitate intercellular communication and are classified as micro- or nano-EVs depending on size. Placental EVs contain molecules associated with cell proliferation and death. In this study, we investigated whether treating human ovarian tumour explants with placental EVs could induce ovarian tumour cell death.

Organoid generation from trophoblast stem cells highlights distinct roles for cytotrophoblasts and stem cells in organoid formation and expansion.

Background: Organoids are stem-cell derived, self-organised, three-dimensional cultures that improve in vitro recapitulation of tissue structure. The generation of trophoblast organoids using primary placental villous digests (containing cytotrophoblasts and trophoblast stem cells (TSC)) improved high-throughput assessment of early trophoblast differentiation. However, the relative contributions of cytotrophoblasts and TSCs to trophoblast organoid growth and differentiation remain unclear, with implications for model interpretation.

Characterizing Extracellular Vesicles Generated from the Integra CELLine Culture System and Their Endocytic Pathways for Intracellular Drug Delivery.

Extracellular vesicles (EVs) have attracted great attention as promising intracellular drug delivery carriers. While the endocytic pathways of small EVs (sEVs, <200 nm) have been reported, there is limited understanding of large EVs (lEVs, >200 nm), despite their potential applications for drug delivery. Additionally, the low yield of EVs during isolation remains a major challenge in their application.

Deep autoencoder as an interpretable tool for Raman spectroscopy investigation of chemical and extracellular vesicle mixtures.

Surface-enhanced Raman spectroscopy (SERS) is a powerful tool that provides valuable insight into the molecular contents of chemical and biological samples. However, interpreting Raman spectra from complex or dynamic datasets remains challenging, particularly for highly heterogeneous biological samples like extracellular vesicles (EVs). To overcome this, we developed a tunable and interpretable deep autoencoder for the analysis of several challenging Raman spectroscopy applications, including synthetic datasets, chemical mixtures, a chemical milling reaction, and mixtures of EVs.

Antiphospholipid-exposed trophoblast-derived extracellular vesicles express elevated levels of TLR7/8-activating microRNAs and induce endometrial endothelial activation, in part, through TLR7.

Women with antiphospholipid syndrome (APS) are at high risk for miscarriage and preeclampsia. Unlike pro-thrombotic systemic APS, obstetric APS is associated with insufficient placentation, as well as inflammation and vascular dysfunction at the maternal-fetal interface. Antiphospholipid antibodies (aPL) can target the placental trophoblast and induce inflammation.

Extracellular vesicles and their effect on vascular haemodynamics: a systematic review.

Extracellular vesicles (EVs) are released from all cell types studied to date and act as intercellular communicators containing proteins, nucleic acids and lipid cargos. They have been shown to be involved in maintaining homoeostasis as well as playing a role in the development of pathology including hypertension and cardiovascular disease. It is estimated that there is 10-10 circulating EVs/mL in the plasma of healthy individuals derived from various sources.

Normotensive placental extracellular vesicles provide long-term protection against hypertension and cardiovascular disease.

Background: Women with normotensive pregnancy are at a reduced risk of developing cardiovascular disease postpartum compared with those who experience hypertensive conditions during pregnancy. However, the underlying mechanisms remain poorly understood. During normotensive pregnancy, vast numbers of placental extracellular vesicles are released into the maternal circulation, which protect endothelial cells from activation and alter maternal vascular tone.

Human placental vascular and perivascular cell heterogeneity differs between first trimester and term, and in pregnancies affected by foetal growth restriction.

Growth-restricted placentae have a reduced vascular network, impairing exchange of nutrients and oxygen. However, little is known about the differentiation events and cell types that underpin normal/abnormal placental vascular formation and function. Here, we used 23-colour flow cytometry to characterize placental vascular/perivascular populations between first trimester and term, and in foetal growth restriction (FGR).

Isolation and Maintenance in Culture of Primary Human Trophoblast from Term Placentae.

Trophoblasts are placenta-specific epithelial cells that play an essential role in conducting nutrient, gas, and waste exchange between the fetus and the mother. Primary culture of human trophoblasts from donated term placentae is an important tool to study placental functions. Currently, there is a lack of general consensus of the optimal culture conditions for maintaining term trophoblast cells in vitro.

The interaction of placental micro-EVs with immune cells in vivo and in vitro.

Problem: Considerable evidence suggests that placental extracellular vesicles (EVs) interact with most types of leukocytes in vitro but in vivo biodistribution studies question whether these interactions are reflective of the situation in vivo.

Method Of Study: CellTracker Red CMTPX stained human placental micro-EVs were isolated from first trimester placental explant cultures. Equivalent amounts of micro-EVs were cultured with murine leukocytes in vitro or injected into pregnant or non-pregnant mice.

Studying exogenous extracellular vesicle biodistribution by in vivo fluorescence microscopy.

Extracellular vesicles (EVs) are lipid-bound vesicles released from cells that play a crucial role in many physiological processes and pathological mechanisms. As such, there is great interest in their biodistribution. One currently accessible technology to study their fate in vivo involves fluorescent labelling of exogenous EVs followed by whole-animal imaging.

A pilot in vivo study: potential ovarian cancer therapeutic by placental extracellular vesicles.

The biological links between cancer and pregnancy are of interest due to parallel proliferative, immunosuppressive, and invasive mechanisms between tumour and placental cells. However, the proliferation and invasion of placental cells are strictly regulated. The understanding of this regulation is largely unknown.

Functionalisation of extracellular vesicles with cyclic-RGDyC potentially for glioblastoma targeted intracellular drug delivery.

With the intrinsic ability to cross the blood-brain barrier, small extracellular vesicles (sEVs) hold promise as endogenous brain-targeted drug delivery nano-platforms for glioblastoma (GBM) treatment. To increase GBM targetability, this study aimed to functionalise sEVs with cyclic arginine-glycine-aspartic acid-tyrosine-cysteine (cRGDyC), a ligand for integrin (αβ) that is overexpressed in GBM cells. Firstly, the intrinsic cellular uptake of sEVs derived from GBM U87 and pancreatic cancer MIA PaCa-2 cells was investigated on the donor cells.

Manifold Learning Enables Interpretable Analysis of Raman Spectra from Extracellular Vesicle and Other Mixtures.

Extracellular vesicles (EVs) have emerged as promising diagnostic and therapeutic candidates in many biomedical applications. However, EV research continues to rely heavily on in vitro cell cultures for EV production, where the exogenous EVs present in fetal bovine (FBS) or other required serum supplementation can be difficult to remove entirely. Despite this and other potential applications involving EV mixtures, there are currently no rapid, robust, inexpensive, and label-free methods for determining the relative concentrations of different EV subpopulations within a sample.

The biodistribution of placental and fetal extracellular vesicles during pregnancy following placentation.

Human pregnancy is a highly orchestrated process requiring extensive cross-talk between the mother and the fetus. Extracellular vesicles released by the fetal tissue, particularly the placenta, are recognized as important mediators of this process. More recently, the importance of placental extracellular vesicle biodistribution studies in animal models has received increasing attention as identifying the organs to which extracellular vesicles are targeted to helps us understand more about this communication system.

Placental Extracellular Vesicles Can Be Loaded with Plasmid DNA.

Recently, extracellular vesicles (EVs) have garnered considerable interest as potential vehicles for drug delivery, including gene therapy. Although EVs from diverse sources have been investigated, current techniques used in the field for EV generation limit large-scale EV production. The placenta is essentially a tissue transplant and has unique properties that allow it to avoid the maternal immune system making it likely that placental EVs will not generate inflammatory responses and will avoid clearance by the immune system.

The Blocking of Integrin-Mediated Interactions with Maternal Endothelial Cells Reversed the Endothelial Cell Dysfunction Induced by EVs, Derived from Preeclamptic Placentae.

Placental extracellular vesicles (EVs) have increasingly been recognized as a major mediator of feto-maternal communication. However, the cellular and molecular mechanisms of the uptake of placental EVs by recipient cells are still not well-understood. We previously reported that placental EVs target a limited number of organs in vivo.

Extracellular Vesicles as Biomarkers and Therapeutics for Inflammatory Eye Diseases.

Extracellular vesicles (EVs) are a group of cell-derived membrane vesicles of varying sizes that can be secreted by most cells. Depending on the type of cell they are derived from, EVs may contain a variety of cargo including proteins, lipids, miRNA, and DNA. Functionally, EVs play important roles in physiological and pathological processes through intercellular communication.

Investigating the consistency of extracellular vesicle production from breast cancer subtypes using CELLine adherent bioreactors.

Extracellular vesicle (EV) research has grown rapidly in recent years, largely due to the potential use of EVs as liquid biopsy biomarkers or therapeutics. However, in-depth characterisation and validation of EVs produced using conventional cultures can be challenging due to the large area of cell monolayers and volumes of culture media required. To overcome this obstacle, multiple bioreactor designs have been tested for EV production with varying success, but the consistency of EVs produced over time in these systems has not been reported previously.

Understanding How Pregnancy Protects Against Ovarian and Endometrial Cancer Development: Fetal Antigens May Be Involved.

It is well known that many factors, including infertility, obesity, type 2 diabetes, and family history of cancer, increase the risk of developing endometrial and ovarian cancer. However, multiparous women are known to have a lower risk of developing either ovarian or endometrial cancer than nonparous women. The lack of ovulation and shifting of sex hormonal balance, with decreased estrogen levels and increased progesterone levels during pregnancy, has traditionally been thought to be the major contributor to this decreased risk.

Production of extracellular vesicles from equine embryo-derived mesenchymal stromal cells.

In Brief: Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) have shown promise as off-the-shelf therapeutics; however, producing them in sufficient quantities can be challenging. In this study, MSCs were isolated from preimplantation equine embryos and used to produce EVs in two commercially available bioreactor designs.

Abstract: Mesenchymal stromal cells (MSC) have recently been explored for their potential use as therapeutics in human and veterinary medicine applications, such as the treatment of endometrial inflammation and infertility.

Conducting Polymer-Coated Carbon Cloth Captures and Releases Extracellular Vesicles by a Rapid and Controlled Redox Process.

Electrochemical techniques offer great opportunities for the capture of chemical and biological entities from complex mixtures and their subsequent release into clean buffers for analysis. Such methods are clean, robust, rapid, and compatible with a wide range of biological fluids. Here, we designed an electrochemically addressable system, based on a conducting terpolymer [P(EDOTEDOTSAcEDOTEG)] coated onto a carbon cloth substrate, to selectively capture and release biological entities using a simple electrochemical redox process.