title: A 3D co-culture microtissue model of the human placenta for nanotoxicity assessment.
abstract: There is increasing evidence that certain nanoparticles (NPs) can overcome the placental barrier, raising concerns on potential adverse effects on the growing fetus. But even in the absence of placental transfer, NPs may pose a risk to proper fetal development if they interfere with the viability and functionality of the placental tissue. The effects of NPs on the human placenta are not well studied or understood, and predictive in vitro placenta models to achieve mechanistic insights on NP-placenta interactions are essentially lacking. Using the scaffold-free hanging drop technology, we developed a well-organized and highly reproducible 3D co-culture microtissue (MT) model consisting of a core of placental fibroblasts surrounded by a trophoblast cell layer, which resembles the structure of the in vivo placental tissue. We could show that secretion levels of human chorionic gonadotropin (hCG) were significantly higher in 3D than in 2D cell cultures, which indicates an enhanced differentiation of trophoblasts grown on 3D MTs. NP toxicity assessment revealed that cadmium telluride (CdTe) and copper oxide (CuO) NPs but not titanium dioxide (TiO2) NPs decreased MT viability and reduced the release of hCG. NP acute toxicity was significantly reduced in 3D co-culture MTs compared to 2D monocultures. Taken together, 3D placental MTs provide a new and promising model for the fast generation of tissue-relevant acute NP toxicity data, which are indispensable for the safe development of NPs for industrial, commercial and medical applications.
authors.affiliation: Particles-Biology Interactions, Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland. tina.buerki@empa.ch.
authors.forename: Carina
authors.initials: C
authors.lastname: Muoth
authors.affiliation: Particles-Biology Interactions, Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland. tina.buerki@empa.ch.
authors.forename: Adrian
authors.initials: A
authors.lastname: Wichser
authors.affiliation: Centre for BioNano Interactions, School of Chemistry and Chemical Biology, University College Dublin, Dublin 4, Ireland.
authors.forename: Marco
authors.initials: M
authors.lastname: Monopoli
authors.affiliation: Research Group for Nano-Bio Science, Division for Food Technology, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark.
authors.forename: Manuel
authors.initials: M
authors.lastname: Correia
authors.affiliation: Research Group for Nano-Bio Science, Division for Food Technology, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark.
authors.forename: Nicky
authors.initials: N
authors.lastname: Ehrlich
authors.affiliation: Research Group for Nano-Bio Science, Division for Food Technology, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark.
authors.forename: Katrin
authors.initials: K
authors.lastname: Loeschner
authors.affiliation: Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, 171 77 Stockholm, Sweden.
authors.forename: Audrey
authors.initials: A
authors.lastname: Gallud
authors.affiliation: Particles-Biology Interactions, Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland. tina.buerki@empa.ch.
authors.forename: Melanie
authors.initials: M
authors.lastname: Kucki
authors.affiliation: Particles-Biology Interactions, Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland. tina.buerki@empa.ch.
authors.forename: Liliane
authors.initials: L
authors.lastname: Diener
authors.affiliation: Particles-Biology Interactions, Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland. tina.buerki@empa.ch.
authors.forename: Pius
authors.initials: P
authors.lastname: Manser
authors.affiliation: Institute of Pathology, Cantonal Hospital St. Gallen, Rorschacherstrasse 95, 9007 St. Gallen, Switzerland.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Jochum
authors.affiliation: Particles-Biology Interactions, Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland. tina.buerki@empa.ch.
authors.forename: Peter
authors.initials: P
authors.lastname: Wick
authors.affiliation: Particles-Biology Interactions, Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland. tina.buerki@empa.ch.
authors.forename: Tina
authors.initials: T
authors.lastname: Buerki-Thurnherr
mesh_terms: D019187:Cadmium Compounds / Q000633:toxicity; D006063:Chorionic Gonadotropin / Q000378:metabolism; D018920:Coculture Techniques; D003300:Copper / Q000633:toxicity; D005260:Female; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D053768:Metal Nanoparticles / Q000633:toxicity*; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D013691:Tellurium / Q000633:toxicity; D014025:Titanium / Q000633:toxicity; D014327:Trophoblasts / Q000166:cytology*
chemical_list: D019187:Cadmium Compounds; D006063:Chorionic Gonadotropin; C009495:titanium dioxide; D003300:Copper; D014025:Titanium; D013691:Tellurium; C028337:cadmium telluride