Ethical considerations for advancing research using organoid models derived from the placenta DOI Creative Commons
Olivier J. M. Schäffers, Joost Gribnau, Bas B. van Rijn

и другие.

Human Reproduction Update, Год журнала: 2025, Номер unknown

Опубликована: Март 3, 2025

Abstract BACKGROUND The advent of organoid culture systems has revolutionized our ability to model and study complex tissues in vitro. placenta is one the last human organs have a functional developed: trophoblast organoids. These 3-dimensional structures, derived from placental tissue, offer researchers valuable tool for studying previously inaccessible processes that occur within womb play significant role determining health offspring. While primarily used research, organoids hold promise clinical applications, including prenatal diagnostics therapeutic interventions, both which may commercial interest. However, ensure research with models conducted responsibly, relevant ethics these need be addressed. OBJECTIVE AND RATIONALE Ethical considerations related placenta, such as are important but remain unexplored literature. Therefore, goal this review explore ethical SEARCH METHODS Since there no specifically addressing date, we based findings on discussions other involving fetal or umbilical cord blood. We employed scoping method search PubMed, Embase, Medline (all), Bioethics Research Library, Google Scholar articles, books, correspondence issues regarding indicated topics, date limits. OUTCOMES can divided into three distinct categories. First, assess moral value organoids, their potential relational symbolic dimensions. Second, it understand associated ownership commercialization Last, appropriate informed consent procedures. It worth noting categories interconnected, second third being largely dependent attributed Future should perspectives various stakeholders, parents who donate tissue research. WIDER IMPLICATIONS This offers insights landscape surrounding derivation products pregnancies, further application, highlighting areas require attention discussion scientific community broader society. REGISTRATION NUMBER N/A.

Язык: Английский

Innate immune signaling in trophoblast and decidua organoids defines differential antiviral defenses at the maternal-fetal interface DOI Creative Commons
Liheng Yang, Eleanor C. Semmes, Cristian Ovies

и другие.

eLife, Год журнала: 2022, Номер 11

Опубликована: Авг. 17, 2022

Infections at the maternal-fetal interface can directly harm fetus and induce complications that adversely impact pregnancy outcomes. Innate immune signaling by both fetal-derived placental trophoblasts maternal decidua must provide antimicrobial defenses this critical without compromising its integrity. Here, we developed matched trophoblast (TO) organoids (DO) from human placentas to define relative contributions of these cells antiviral interface. We demonstrate TO DO basally secrete distinct immunomodulatory factors, including constitutive release type III interferon IFN-λ2 TOs, differentially respond viral infections through induction organoid-specific factors. Finally, differential susceptibility innate cytomegalovirus (HCMV) develop a co-culture model which showed trophoblast-derived factors protect decidual HCMV infection. Our findings establish as ex vivo models study vertically transmitted highlight differences in decidua.

Язык: Английский

Процитировано

73
Landscape of human organoids: Ideal model in clinics and research DOI Creative Commons
Xinxin Han, Chunhui Cai, Wei Deng

и другие.

The Innovation, Год журнала: 2024, Номер 5(3), С. 100620 - 100620

Опубликована: Апрель 1, 2024

In the last decade, organoid research has entered a golden era, signifying pivotal shift in biomedical landscape. The year 2023 marked milestone with publication of thousands papers this arena, reflecting exponential growth. However, amid burgeoning expansion, comprehensive and accurate overview field been conspicuously absent. Our review is intended to bridge gap, providing panoramic view rapidly evolving We meticulously analyze from eight distinctive vantage points, harnessing our rich experience academic research, industrial application, clinical practice. present deep exploration advances technology, underpinned by long-standing involvement arena. narrative traverses historical genesis organoids their transformative impact across various sectors, including oncology, toxicology, drug development. delve into synergy between avant-garde technologies such as synthetic biology single-cell omics discuss role tailoring personalized medicine, enhancing high-throughput screening, constructing physiologically pertinent disease models. analysis reflective discourse provide dive existing landscape emerging trends technology. spotlight technological innovations, methodological evolution, broadening spectrum applications, emphasizing revolutionary influence discovery, other fields. Looking ahead, we cautiously anticipate future developments especially its potential implications for patient care, new avenues research. trust that will be an asset researchers, clinicians, patients keen interest medical strategies. offer broad prospective capabilities encompassing wide range current applications. summary, attempt field. reflections, summaries, projections might useful researchers hope contribute shaping trajectory dynamic advancing

Язык: Английский

Процитировано

34
Zika virus NS1 drives tunneling nanotube formation for mitochondrial transfer and stealth transmission in trophoblasts DOI Creative Commons
Rafael Tomoya Michita, Long Tran, Steven J. Bark

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 20, 2025

Zika virus (ZIKV) is unique among orthoflaviviruses in its vertical transmission capacity humans, yet the underlying mechanisms remain incompletely understood. Here, we show that ZIKV induces tunneling nanotubes (TNTs) placental trophoblasts which facilitate transfer of viral particles, proteins, mitochondria, and RNA to neighboring uninfected cells. TNT formation driven exclusively via non-structural protein 1 (NS1). Specifically, N-terminal 1-50 amino acids membrane-bound NS1 are necessary for triggering host Trophoblasts infected with TNT-deficient ZIKVΔTNT mutant elicited a robust antiviral IFN-λ 1/2/3 response relative WT ZIKV, suggesting TNT-mediated trafficking allows cell-to-cell camouflaged from defenses. Using affinity purification-mass spectrometry cells expressing wild-type or non-TNT forming NS1, found mitochondrial proteins dominant NS1-interacting partners. We demonstrate infection expression elevated mitochondria levels siphoned TNTs healthy ZIKV-infected Together our findings identify stealth mechanism employs intercellular spread trophoblasts, evasion interferon response, hijacking augment propagation survival offers basis novel therapeutic developments targeting these interactions limit dissemination.

Язык: Английский

Процитировано

3
A comprehensive review of human trophoblast fusion models: recent developments and challenges DOI Creative Commons
Xia Li, Zhuo‐Hang Li, Ying-Xiong Wang

и другие.

Cell Death Discovery, Год журнала: 2023, Номер 9(1)

Опубликована: Окт. 10, 2023

As an essential component of the maternal-fetal interface, placental syncytiotrophoblast layer contributes to a successful pregnancy by secreting hormones necessary for pregnancy, transporting nutrients, mediating gas exchange, balancing immune tolerance, and resisting pathogen infection. Notably, deficiency in mononuclear trophoblast cells fusing into multinucleated has been linked adverse outcomes, such as preeclampsia, fetal growth restriction, preterm birth, stillbirth. Despite availability many models study fusion, there exists notable disparity from ideal model, limiting deeper exploration development. Here, we reviewed existing employed investigation human fusion several aspects, including development history, latest progress, advantages, disadvantages, scope application, challenges. The literature searched covers monolayer cell lines, primary trophoblast, explants, stem cells, pluripotent three-dimensional spheres, organoids, placenta-on-a-chip 1938 2023. These diverse have significantly enhanced our comprehension regulation underlying mechanisms placental-related disorders. Through this review, objective is provide readers with thorough understanding models, making it easier select most suitable address specific experimental requirements or scientific inquiries. Establishment application models.

Язык: Английский

Процитировано

37
Trophoblast organoids with physiological polarity model placental structure and function DOI Creative Commons
Liheng Yang, Pengfei Liang, Huanghe Yang

и другие.

Journal of Cell Science, Год журнала: 2023, Номер 137(5)

Опубликована: Сен. 7, 2023

Human trophoblast organoids (TOs) are a three-dimensional ex vivo culture model that can be used to study various aspects of placental development, physiology and pathology. However, standard culturing TOs does not recapitulate the cellular orientation chorionic villi in given multi-nucleated syncytiotrophoblast (STB) develops largely within inner facing surfaces these (STBin). Here, we developed method under conditions vivo. We show STBin suspension with gentle agitation leads development containing STB on outer surface (STBout). Using membrane capacitance measurements, determined outermost STBout contain large syncytia comprising >50 nuclei, whereas small (<10 nuclei) mononuclear cells. The growth mimic thus allows for variety biology physiological conditions.

Язык: Английский

Процитировано

32
Immune surveillance of cytomegalovirus in tissues DOI Creative Commons
Andrea Mihalić, Jelena Železnjak, Berislav Lisnić

и другие.

Cellular and Molecular Immunology, Год журнала: 2024, Номер 21(9), С. 959 - 981

Опубликована: Авг. 12, 2024

Abstract Cytomegalovirus (CMV), a representative member of the Betaherpesvirinae subfamily herpesviruses, is common in human population, but immunocompetent individuals are generally asymptomatic when infected with this virus. However, immunocompromised and immunologically immature fetuses newborns, CMV can cause wide range often long-lasting morbidities even death. not only widespread throughout population it also its hosts, infecting establishing latency nearly all tissues organs. Thus, understanding pathogenesis immune responses to virus prerequisite for developing effective prevention treatment strategies. Multiple arms system engaged contain infection, general concepts control now reasonably well understood. Nonetheless, recent years, tissue-specific have emerged as an essential factor resolving infection. As differ biology function, so do pathological processes during This review discusses state-of-the-art knowledge response infection tissues, particular emphasis on several well-studied most commonly affected

Язык: Английский

Процитировано

10
Spatial single-cell analysis identifies placental villi structural and immune remodeling across gestation DOI Creative Commons
Suganthinie Velagala,

Long Phan,

Chino Eke

и другие.

Mucosal Immunology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Pregnancies rely upon the balance between fetal and maternal immune systems. Employing imaging mass cytometry, this study creates a spatial map landscape to unravel cellular dynamics within placental villi (PV). Consistent with previous data we report structural remodeling in PV, highlighted by increased syncytial trophoblasts, vascular smooth muscle cells, endothelial cells term PV. Additionally, identified that rare populations including dendritic innate lymphoid myeloid-derived suppressor mid-gestation were more abundant activated than placentas, suggesting potentially tolerogenic state. Conversely, various macrophage subtypes combination T-cells exhibited heightened activation markers, possibly indicating signaling preparation for parturition. In mid-gestation, fibroblasts had interactions while samples close adjacencies macrophages. This offers insights into PV composition changes mid full-term samples, providing foundation future studies understand mechanisms of preterm birth other pregnancy complications.

Язык: Английский

Процитировано

1
Malaria in Pregnancy: From Placental Infection to Its Abnormal Development and Damage DOI Creative Commons

Caroline Lin Lin Chua,

Sebastian Kah Ming Khoo,

Jun Long Ernest Ong

и другие.

Frontiers in Microbiology, Год журнала: 2021, Номер 12

Опубликована: Ноя. 11, 2021

Malaria remains a global health burden with Plasmodium falciparum accounting for the highest mortality and morbidity. in pregnancy can lead to development of placental malaria, where P. -infected erythrocytes adhere receptors, triggering inflammation subsequent damage, causing harm both mother her infant. Histopathological studies placentas revealed various abnormalities such as excessive perivillous fibrinoid deposits, breakdown syncytiotrophoblast integrity, trophoblast basal lamina thickening, increased syncytial knotting, accumulation mononuclear immune cells within intervillous spaces. These events turn, are likely impair function, ultimately insufficiency, intrauterine growth restriction, preterm delivery low birth weight. Hence, better understanding mechanisms behind alterations damage during malaria is needed design effective interventions. In this review, using evidence from human murine models, an integrated view on potential underlying pathologies provided. The molecular, immunological metabolic changes infected that reflect their responses parasitic infection injury discussed. Finally, models be used by researchers improve our pathogenesis presented.

Язык: Английский

Процитировано

55
Functional coupling between TRPV4 channel and TMEM16F modulates human trophoblast fusion DOI Creative Commons
Yang Zhang, Pengfei Liang, Liheng Yang

и другие.

eLife, Год журнала: 2022, Номер 11

Опубликована: Июнь 7, 2022

TMEM16F, a Ca 2+ -activated phospholipid scramblase (CaPLSase), is critical for placental trophoblast syncytialization, HIV infection, and SARS-CoV2-mediated however, how TMEM16F activated during cell fusion unclear. Here, using trophoblasts as model fusion, we demonstrate that influx through the permeable transient receptor potential vanilloid channel TRPV4 activation plays role in subsequent human fusion. GSK1016790A, specific agonist, robustly activates trophoblasts. We also show are functionally coupled within microdomains line patch-clamp electrophysiology. Pharmacological inhibition or gene silencing of hinders syncytialization. Our study uncovers functional expression one physiological mechanisms trophoblasts, thus providing us with novel strategies to regulate CaPLSase activity checkpoint physiologically disease-relevant events.

Язык: Английский

Процитировано

31
Acute response to pathogens in the early human placenta at single-cell resolution DOI Creative Commons
Regina Hoo, Elias R. Ruiz-Morales, Iva Kelava

и другие.

Cell Systems, Год журнала: 2024, Номер 15(5), С. 425 - 444.e9

Опубликована: Май 1, 2024

The placenta is a selective maternal-fetal barrier that provides nourishment and protection from infections. However, certain pathogens can attach to even cross the placenta, causing pregnancy complications with potential lifelong impacts on child's health. Here, we profiled at single-cell level placental responses three associated intrauterine complications—Plasmodium falciparum, Listeria monocytogenes, Toxoplasma gondii. We found upon exposure pathogens, all lineages trigger inflammatory may compromise function. Additionally, characterized of fetal macrophages known as Hofbauer cells (HBCs) each pathogen propose they are probable niche for T. Finally, revealed how P. falciparum adapts microenvironment by modulating protein export into host erythrocyte nutrient uptake pathways. Altogether, have defined cellular networks signaling pathways mediating acute could contribute complications.

Язык: Английский

Процитировано

9