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

Richa Hoy

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Ноя. 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.

Язык: 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

и другие.

Extracellular Vesicle, Год журнала: 2024, Номер 3, С. 100035 - 100035

Опубликована: Фев. 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

Язык: Английский

Процитировано

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

Konstantina Tetorou,

Natalie Suff

и другие.

American Journal Of Pathology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1
Regulatory roles of extracellular vesicles in pregnancy complications DOI Creative Commons
Qian Sun, Hua Chang, Huan Wang

и другие.

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Фев. 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.

Язык: Английский

Процитировано

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

Rumeng Lin,

Bingyong Mao

и другие.

Biomolecules, Год журнала: 2024, Номер 14(2), С. 240 - 240

Опубликована: Фев. 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.

Язык: Английский

Процитировано

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

и другие.

Diseases, Год журнала: 2024, Номер 12(3), С. 59 - 59

Опубликована: Март 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.

Язык: Английский

Процитировано

5
Cargo exchange between human and bacterial extracellular vesicles in gestational tissues: a new paradigm in communication and immune development DOI Open Access
Emmanuel Amabebe,

Awanit Kumar,

Madhuri Tatiparthy

и другие.

Extracellular Vesicles and Circulating Nucleic Acids, Год журнала: 2024, Номер 5(2), С. 297 - 328

Опубликована: Июнь 18, 2024

Host-bacteria and bacteria-bacteria interactions can be facilitated by extracellular vesicles (EVs) secreted both human bacterial cells. Human EVs (BEVs) propagate transfer immunogenic cargos that may elicit immune responses in nearby or distant recipient cells/tissues. Hence, direct colonization of tissues cells is not required for stimulation. This phenomenon important the feto-maternal interface, where optimum tolerance between mother fetus a successful pregnancy. Though intrauterine cavity widely considered sterile, BEVs from diverse sources have been identified placenta amniotic cavity. These internalized cells, which help them evade host surveillance. it appears logical, whether internalize EV cargo yet to determined. However, presence placental believed trigger low-grade response primes fetal system ex-utero survival, but insufficient disrupt progression pregnancy cause intolerance adverse events. Nevertheless, exchange bioactive BEVs, mechanical underpinnings health implications such interactions, especially during pregnancy, are still understudied. Therefore, while focusing on we discussed how take up their cargo, cell (feto-maternal) inflammatory BEV stimulation, associations these with priming reproductive outcomes as preeclampsia preterm birth.

Язык: Английский

Процитировано

3
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

и другие.

Expert Opinion on Drug Delivery, Год журнала: 2025, Номер unknown, С. 1 - 3

Опубликована: Янв. 4, 2025

Язык: Английский

Процитировано

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

Brinley Harrington,

Tilu Jain Thomas,

Madhuri Tatiparthy

и другие.

Extracellular Vesicle, Год журнала: 2025, Номер 5, С. 100066 - 100066

Опубликована: Янв. 24, 2025

Язык: Английский

Процитировано

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

и другие.

Journal of Controlled Release, Год журнала: 2025, Номер unknown, С. 113796 - 113796

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

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

и другие.

The FASEB Journal, Год журнала: 2025, Номер 39(10)

Опубликована: Май 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.

Язык: Английский

Процитировано

0