Fetal microchimeric cells influence maternal lung health following term and preterm births DOI Creative Commons
Ananth Kumar Kammala, Ryan C. V. Lintao,

Richa Hoy

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 18, 2024

Fetal microchimerism, the presence of fetal cells in maternal tissues, has garnered interest for its potential role physiology. In this study, we aimed to explore impact microchimeric on lung health following term and preterm delivery, particularly context infection-induced birth subsequent allergic challenges. We characterized immune lungs using a transgenic mouse model (mT+ Ve, Td Tomato) high dimensional mass cytometry (CyTOF) techniques. evaluated their influence function inflammation. Our findings revealed distinct differences cell composition between deliveries. Mice delivered significantly increased fetal-specific cells, such as activated macrophages Tbet + Ve memory B-cells, compared term-delivered mice. Conversely, deliveries showed elevated levels CD4 cells. Furthermore, preterm-delivered dams demonstrated heightened airway hyperresponsiveness, pro-inflammatory cytokine expression, cellular infiltration, mucous production dams. Co-culture experiments that from births stimulated inflammatory cytokines IL-6 TNF-α epithelial These shed light complex dynamics postpartum complications after birth. Understanding these mechanisms could provide insights targeted interventions improve at-risk populations.

Language: Английский

A multi-organ, feto-maternal interface organ-on-chip, models pregnancy pathology and is a useful preclinical extracellular vesicle drug trial platform DOI Creative Commons

Melody Safarzadeh,

Lauren Richardson, Ananth Kumar Kammala

et al.

Extracellular Vesicle, Journal Year: 2024, Volume and Issue: 3, P. 100035 - 100035

Published: Feb. 22, 2024

Pregnant women and their fetuses are often excluded from clinical trials due to missing drug-related pre-clinical trial information at the human feto-maternal interface (FMi). The two interfaces-placenta/decidua fetal membranes/decidua gatekeepers of drug transport; however, testing functions is impractical during pregnancy. Limitations current in-vivo/in-vitro models have hampered development Hence, major complications like preterm births maternal neonatal mortalities remain high. Advancements in organ-on-chip (OOC) platforms test kinetics efficacy novel extracellular vesicle-based delivery expected accelerate preclinical related pregnancy complications. Here we report a humanized multi-organ membrane/placenta (fetal)-decidua (maternal) OOC (FMi-PLA-OOC) that contains seven cell types interconnected through microchannels maintain intercellular interactions as seen in-utero. Cytotoxicity, propagation, mechanism action, engineered vesicles containing anti-inflammatory interleukin (IL)-10 (eIL-10) were evaluated reduce FMi inflammation associated with birth. A healthy disease model (lipopolysaccharide-infectious inflammation) FMi-PLA-OOC was created co-treated eIL-10. eIL-10 propagated side within 72-h, localized all types, showed no cytotoxicity, activated IL-10 signaling pathways, reduced lipopolysaccharide-induced (minimized NF-kB activation proinflammatory cytokine production). These data recapitulated eIL-10s' ability delay infection-associated birth mouse models, suggesting an alternative approach using animal models. Additionally, utility can traverse FMis inflammation-associated

Language: Английский

Citations

10
Ascending vaginal infection in mice induces preterm birth and neonatal morbidity DOI Creative Commons
Ashley K. Boyle,

Konstantina Tetorou,

Natalie Suff

et al.

American Journal Of Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
Lactobacillus crispatus CCFM1339 Inhibits Vaginal Epithelial Barrier Injury Induced by Gardnerella vaginalis in Mice DOI Creative Commons
Xiaoyan Huang,

Rumeng Lin,

Bingyong Mao

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(2), P. 240 - 240

Published: Feb. 18, 2024

The vaginal epithelial barrier, which integrates mechanical, immune, chemical, and microbial defenses, is pivotal in safeguarding against external pathogens upholding the microecological equilibrium. Although widely used metronidazole effectively curtails Gardnerella vaginalis, a key pathogen bacterial vaginosis, it falls short restoring barrier or reducing recurrence rates. Our prior research highlighted Lactobacillus crispatus CCFM1339, vaginally derived strain, for its capacity to modulate barrier. In cellular models, L. CCFM1339 fortified integrity of monolayer, augmented migration, facilitated repair. Remarkably, animal substantially abated secretion disruption biomarker E-cadherin (from 101.45 82.90 pg/mL) increased anti-inflammatory cytokine IL-10 (35.18% vs. model), consequently mitigating inflammation mice. Immunological assays tissues elucidated secretory IgA levels 405.56 740.62 ng/mL) curtailed IL-17 gene expression. Moreover, enhanced Lactobacilli abundance attenuated Enterobacterium Enterococcus within microbiome, underscoring potential probiotic applications regulation.

Language: Английский

Citations

6
Collateral Damage in the Placenta during Viral Infection in Pregnancy: A Possible Mechanism for Vertical Transmission and an Adverse Pregnancy Outcome DOI Creative Commons

Víctor Javier Cruz-Holguín,

Luis Didier González-García,

Manuel Adrían Velazquez-Cervantes

et al.

Diseases, Journal Year: 2024, Volume and Issue: 12(3), P. 59 - 59

Published: March 20, 2024

In mammals, the placenta is a connection between mother and new developing organism. This tissue has protective function against some microorganisms, transports nutrients, exchanges gases excretory substances fetus. Placental mainly composed of chorionic villi functional units called trophoblasts (cytotrophoblasts, syncytiotrophoblast, extravillous trophoblasts). However, viruses have developed mechanisms that help them invade placenta, causing various conditions such as necrosis, poor perfusion, membrane rupture which, in turn, can impact development fetus put mother’s health at risk. this study, we collected most relevant information about viral infection during pregnancy which affect both fetus, leading to an increase probability vertical transmission. Knowing these could be for research maternal–fetal context may provide options therapeutic targets biomarkers fetal prognosis.

Language: Английский

Citations

5
How can we advance drug delivery options using extracellular vesicles for pregnant women to reduce preterm birth? DOI Creative Commons
Ramkumar Menon, Lauren Richardson, Ananth Kumar Kammala

et al.

Expert Opinion on Drug Delivery, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 3

Published: Jan. 4, 2025

Language: Английский

Citations

0
Exosomal delivery of IL-10: Biodistribution, pharmacokinetics, and preterm birth prevention strategies DOI

Brinley Harrington,

Tilu Jain Thomas,

Madhuri Tatiparthy

et al.

Extracellular Vesicle, Journal Year: 2025, Volume and Issue: 5, P. 100066 - 100066

Published: Jan. 24, 2025

Language: Английский

Citations

0
Regulatory roles of extracellular vesicles in pregnancy complications DOI Creative Commons
Qian Sun, Hua Chang, Huan Wang

et al.

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Extracellular vesicles (EVs) are heterogeneous membranous structures released by various cell types, including large vesicles, microvesicles (MVs), and exosomes. These play crucial roles in intercellular communication within interstitial fluids involved numerous physiological pathological processes. This review aims to examine the regulatory of EVs pregnancy complications, focusing on their involvement gestational diabetes mellitus (GDM), preeclampsia (PE), preterm birth (PTB). Placenta- embryo-derived have gained significant attention for biological due effects inflammation, immune response immunomodulation. Recent research highlights importance embryonic development gestation. During pregnancy, several functioned complex endocrine regulation complications that can affect both mother fetus, with long-term cardiovascular metabolic risks. discusses current evidence how modulate outcomes explores pathology GDM, PE, PTB. In spite difficulties relating these findings pathogenesis insufficient clinical practice, potential impact specific proteins miRNAs transported is noteworthy emergence complications. Future should continue explore interactions mediated develop novel diagnostic therapeutic strategies pregnancy-related disorders.

Language: Английский

Citations

0
Extracellular vesicle as therapeutic agents in anti-aging: Mechanistic insights and future potential DOI
Hwi Yoon, JiHun Jo, Hyesun Hyun

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown, P. 113796 - 113796

Published: May 1, 2025

Language: Английский

Citations

0
Exosomal Delivery of Interleukin‐10 Reduces Infection‐Associated Inflammation in a 3D‐Printed Model of a Humanized Feto–Maternal Interface DOI

Leah Saylor,

Rahul Cherukuri, Ananth Kumar Kammala

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(10)

Published: May 13, 2025

ABSTRACT Spontaneous preterm birth (PTB) is associated with fetal inflammatory responses that are due to infections. Effective interventions minimize these limited as drugs do not usually cross the feto–maternal interface (FMi) barrier, and reliable models test drug efficacy other pharmacologic parameters have been available. We leveraged New Approach Methods (NAMs), including employing extracellular vesicles (exosomes of 30–200 nm) deliver anti‐inflammatory cytokine interleukin (IL)‐10 using a high‐throughput 3D‐printed FMi model this delivery. IL‐10 encapsulated exosomes were prepared by encapsulating recombinant (rIL‐10) electroporation (eIL‐10) or transfecting RAW264.7 cells an IL‐10‐expression plasmid (tIL‐10) enabled expression in during exosome biogenesis, which was then collected. Using biocompatible polymer resin, we 3D printed two‐chambered scaffold mimic amnion–decidual (feto–maternal) interface. Microchannels integrated into lower portions facilitate intercellular communication. The device composed mix gelatin methacrylate hydrogel material (lower part) cell‐specific culture medium (upper part). showed empty IL‐10‐loaded delivered maternal side able our device. Furthermore, effectiveness eIL‐10 tIL‐100 (500 ng) reducing LPS‐induced inflammation on both sides demonstrated measuring pro‐inflammatory IL‐6 IL‐8 concentrations via multiplex assays at 6 h 24 timepoints. determined two‐chamber propagation between interconnected chambers. LPS treatment decidua induced ( p < 0.001) amnion compared healthy (control) conditions. Co‐treatment along exosomes, regardless its formulation, significantly reduced levels cytokines after A used show can reduce infection‐induced inflammation. describe two NAMs potential improve perinatal medicine: (1) exosomal delivery method protects barriers (2) be for screening.

Language: Английский

Citations

0
IL-1 and TNF mediates IL-6 signaling at the maternal-fetal interface during intrauterine inflammation DOI Creative Commons
Pietro Presicce,

Cynthia Roland,

Paranthaman Senthamaraikannan

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 4, 2024

Introduction IL6 signaling plays an important role in triggering labor and is established biomarker of intrauterine infection/inflammation (IUI) driven preterm (PTL). The biology during IUI at the maternal-fetal interface was investigated samples from human subjects non-human primates (NHP). Methods Pregnant women with histologic chorioamnionitis diagnosed by placenta histology were recruited (n=28 term, n=43 for pregnancies 26-36 completed weeks gestation). induced Rhesus macaque intraamniotic injection lipopolysachharide (LPS, n=23). IL1 blocked using Anakinra (human IL-1 receptor antagonist, n=13), Tumor necrosis factor (TNF) anti TNF-antibody (Adalimumab n=14). blockers given before LPS. All animals including controls (intraamniotic saline n=27), delivered 16h after LPS/saline exposure about 80% gestation. Results a robust expression mRNAs fetal membranes (chorion-amnion-decidua tissue) both humans (term preterm) NHP. major sources mRNA amnion mesenchymal cells (AMC) decidua stroma cells. Additionally, NHP, ADAM17 (a protease that cleaves membrane bound (IL6R) to release soluble form) IL6R increased membranes, ratio forms IL6R, gp130 amniotic fluid signifying upregulation trans-signaling. Both TNF blockade suppressed LPS-induced AMC variably decreased elements Discussion These data suggest may be useful anti-inflammatory agents via suppression interface.

Language: Английский

Citations

2