Biology subjects

Yankello, H.

Publications and source records attributed to Yankello, H..

3 recordsLinked to original sources

bioRxiv2024

Scoping Review of Maternal Monocytes and the Syncytiotrophoblast: Bi-Directional Communication in the Intervillous Space

The relationship between maternal monocytes and the placenta is crucial for successful pregnancy. As existing reviews focus on the research on decidual macrophages or Hofbauer cells (fetal macrophages), we conducted a scoping review of literature studies examining the relationship between circulating maternal monocytes and the villous trophoblast. The goal of this review was to outline existing research within the field, disseminate further information, and to identify current knowledge gaps within the field. We searched the PubMed (MEDLINE) database for relevant articles published since 1995 that studied human tissue or cell lines. Our results showed clear trends in the type of monocyte and placental primary tissues and cell lines used. Further classification of these articles revealed four primary categories of monocyte-trophoblast interaction research: monocyte presence or recruitment to the placenta, monocyte phenotype in the intervillous space, monocyte-placental adhesion, and monocyte interaction with syncytiotrophoblast-derived extracellular vesicles (STBEVs). Although limited in scope and number, these studies implicate the importance of monocyte-trophoblast interactions, and their significant roles in maternal disease.

immunology↗

bioRxiv2023

Bi-directional communication between monocytes and trophoblasts under hypoxia and hypoxia-reperfusion conditions

IntroductionPregnancy-related disorders such as preeclampsia are associated with syncytiotrophoblast (STB) stress and monocyte dysregulation. It remains unclear whether this stress derives from prolonged placental hypoxia or a hypoxia-reperfusion-type injury. Thus, this study investigated how these two models of STB stress impact trophoblast-monocyte interactions. MethodCobalt chloride chemically induced hypoxia in BeWo b30 cells. A transwell coculture system was used to examine trophoblast-monocyte signaling. qPCR quantified gene expression changes following coculture. Monocyte phagocytosis of E. Coli or adhesion to placental cells was determined via flow cytometry. Monocyte migration to placental signals was quantified using a cell counter. ResultsCobalt chloride induced a hypoxic state in BeWo b30s. Reperfusion restored the expression of indirect hypoxia genes and ER stress genes. Coculturing THP-1 monocytes with normoxic, hypoxic, and hypoxic-reperfused BeWo b30s promoted b30 survival but not wound-healing capacity. Compared to hypoxic-reperfused BeWos, hypoxic cells increased monocyte adhesion and inflammatory gene expression, decreased monocyte phagocytosis, and did not change monocyte migration. Finally, placental signaling in early-onset PE decreased monocyte chemotaxis, but monocyte precondition more strongly influenced migration compared to placental state. DiscussionOverall, hypoxic placental signals most effectively recapitulate monocyte functional behavior observed in preeclampsia. Further research is needed to understand spatial and temporal changes in monocyte-trophoblast interactions and pregnancy outcomes. Monocyte chemotaxis to primary placental signals varied by gestational age, maternal diagnosis, and monocyte condition, implying monocytes could be used as functional biomarkers to predict their behavior at the maternal-fetal interface as well as the onset of disease. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/558721v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@15dae34org.highwire.dtl.DTLVardef@157dec7org.highwire.dtl.DTLVardef@1e2db81org.highwire.dtl.DTLVardef@b90ab6_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2021

Extracellular Vesicles Deliver Mitochondria and HSP27 Protein to Protect the Blood-Brain Barrier

Ischemic stroke causes brain endothelial cell (BEC) death and damages tight junction integrity of the blood-brain barrier (BBB). We harnessed the innate mitochondrial load of endothelial cell-derived extracellular vesicles (EVs) and utilized mixtures of EV/exogenous heat shock protein 27 (HSP27) as a one-two punch strategy to increase BEC survival (via EV mitochondria) and preserve their tight junction integrity (via HSP27 effects). We demonstrated that the medium-to-large (m/lEV) but not small EVs (sEV) transferred their mitochondrial load, which subsequently colocalized with the mitochondrial network of the recipient primary human BECs. BECs treated with m/lEVs increased relative ATP levels and displayed superior mitochondrial function. Importantly, m/lEVs isolated from oligomycin (mitochondrial complex V inhibitor) or rotenone (mitochondrial complex I inhibitor)-exposed BECs (RTN-m/lEVs or OGM-m/lEVs) did not increase BECs ATP levels compared to naive m/lEVs. In contrast, RTN-sEV and OGM-sEV functionality in increasing cellular ATP levels was minimally impacted in comparison to naive sEVs. Intravenously administered m/lEVs showed a reduction in brain infarct sizes compared to vehicle-injected mice in a mouse middle cerebral artery occlusion model of ischemic stroke. We formulated binary mixtures of human recombinant HSP27 protein with EVs: EV/HSP27 and ternary mixtures of HSP27 and EV with cationic polymer poly (ethylene glycol)-b-poly (diethyltriamine): (PEG-DET/HSP27)/EV. (PEG-DET/HSP27)/EV and EV/HSP27 mixtures decreased the paracellular permeability of small and large molecular mass fluorescent tracers in oxygen glucose-deprived primary human BECs. This one-two-punch approach to increase BEC metabolic function and tight junction integrity is a promising strategy for BBB protection and prevention of long-term neurological dysfunction post-ischemic stroke. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/466491v5_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@dc5493org.highwire.dtl.DTLVardef@134ad7forg.highwire.dtl.DTLVardef@16a8929org.highwire.dtl.DTLVardef@15315bc_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIMedium-to-large extracellular vesicles (m/lEVs), not small EVs contain mitochondria C_LIO_LIm/lEVs increased ATP and mitochondrial function in brain endothelial cells (BECs) C_LIO_LIm/lEVs from oligomycin-exposed BECs did not increase recipient BEC ATP levels C_LIO_LIIntravenously injected m/lEVs reduced brain infarct sizes in a mouse stroke model C_LIO_LIEV/HSP27 mixtures reduced small and large dextran molecule permeability across BECs C_LI

bioengineering↗