Development of a human iPSC-derived placental barrier-on-chip model

نویسندگان

چکیده

•A 3D perfused placental barrier with high integrity differentiated from hiPSC•On-chip differentiation improved the spatial organization and directionality•Detection of endocrine, fusogenic markers transporters•3D microfluidic format boosted mechanosensing cell surface receptor signaling Although recently developed placenta-on-chip systems opened promising perspectives for modeling, they still lack physiologically relevant trophoblasts are poorly amenable to high-throughput studies. We aimed implement human-induced pluripotent stem cells (hiPSC)-derived into a multi-well device develop scalable model. When cultured in micro-channel against collagen-based matrix, hiPSC-derived self-arranged structure showing invasive behavior, endocrine activities, structural integrity, expressing transporters. RNA-seq analysis revealed that environment expression genes related early development, mainly involved signaling. These results demonstrated feasibility generating primitive syncytium hiPSC platform. Besides expanding trophoblast scope applications, this study constitutes an important resource improve models boost research therapeutics evaluation pregnancy. The placenta is composed multi-layer specialized fetal origin working together support developing fetus. Shortly after implantation, layer actively proliferating cytotrophoblasts (CTB) can either differentiate syncytiotrophoblasts (STBs) or extravillous (EVTs). STB form multinucleated outer layer, called syncytium, directly bathing maternal blood constituting area exchanges between circulations.1Knöfler M. Haider S. Saleh L. Pollheimer J. Gamage T.K.J.B. James Human development: key molecular mechanisms model systems.Cell. Mol. Life Sci. 2019; 76: 3479-3496https://doi.org/10.1007/s00018-019-03104-6Crossref PubMed Scopus (285) Google Scholar In particular, provides essential selective regulating fetomaternal transfer physiologic compounds xenobiotics, protecting growing fetus pathogen entry secreting hormones necessary successful pregnancy outcome. EVT highly migratory remodeling spiral arteries.1Knöfler Developing more human vitro step our ability conduct as well provide new methods assess potential drug toxicity. Several severe complications including preeclampsia intra-uterine growth restriction associated dysfunction formation release syncytial products such anti-angiogenic factors.2Knerr I. Beinder E. Rascher W. Syncytin, novel endogenous retroviral gene placenta: Evidence its dysregulation HELLP syndrome.Am. Obstet. Gynecol. 2002; 186: 210-213https://doi.org/10.1067/mob.2002.119636Abstract Full Text PDF (120) Scholar,3Guller Ma Y.Y. Fu H.H. Krikun G. Abrahams V.M. 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ژورنال

عنوان ژورنال: iScience

سال: 2023

ISSN: ['2589-0042']

DOI: https://doi.org/10.1016/j.isci.2023.107240