Fig. 7

Mimicking placental function on the chip. (A) Schematic of the human placenta chip model. Human umbilical vein endothelial cells (HUVECs) and trophoblast cells were co-cultured to mimic the placental barrier interface between the mother and the fetus. Reproduced with permission [86]. Copyright 2020 Mosavati, Oleinikov and Du. (B) The placenta is implanted in the maternal decidua during the first trimester of pregnancy, with syncytiotrophoblasts (STBs) located on the outer surface of the placenta in direct contact with the maternal blood, and cytotrophoblasts (CTBs) located on the inner surface of the placenta. Fetal extravillous trophoblasts (EVTs) detach from the placenta and invade the maternal decidua to remodel the uterine spiral arteries. Maternal leukocytes present at the maternal-fetal interface, including decidual natural killer (dNK) cells, may regulate trophoblast invasion and spiral artery transformation through the secretion of cytokines (e.g., GM-CSF). Reproduced with permission [105]. Copyright 2017 Abbas, Oefner, Polacheck, Gardner, Farrell, Sharkey, Kamm, Moffett and Oyen. (C) Schematic of the placenta trophoblast-endothelial interface and placenta organ-on-a-chip (PLA-OOC). The PLA-OOC contains three rectangular cell culture chambers separated by arrays of microchannels. The cells are seeded as follows, from left to right: syncytiotrophoblasts (yellow), the center chamber contains cytotrophoblasts (pink), and the right chamber contains human umbilical vein endothelial cells (HUVECs) forming the endothelial layer (blue). Reproduced with permission [90]. Copyright 2022 Richardson, Kammala, Costantine, Fortunato, Radnaa, Kim, Taylor, Han and Menon. (D) Microfluidics as a model for trophoblast invasion. EVTs are isolated from first trimester placentas, embedded in growth factor-reduced Matrigel in the central hydrogel channel. A constant flow of medium is applied in the two side channels, one with (channel A) and without GM-CSF (channel B) to create a gradient of the cytokine across the hydrogel channel. Reproduced with permission [105]. Copyright 2017 Abbas, Oefner, Polacheck, Gardner, Farrell, Sharkey, Kamm, Moffett and Oyen. (E) A bioengineered placental barrier model was constructed in a perfused organ-on-a-chip system. The human trophectodermal stem cells were inoculated on the upper channel, where they could differentiate into cytotrophoblasts and syncytiotrophoblasts and self-assemble into a double-layered trophoblast epithelium with a placental microvillus-like structure under dynamic culture conditions. Human umbilical vein endothelial cells were cultured on the other side of the collagen-coated membrane to mimic the fetal endothelium. Reproduced with permission [108]. Copyright 2023 Cao, Wang, Liu, Rong and Qin