Induced pluripotent stem cell-derived vascular networks to screen nano–bio interactions
| Autor: | Helena Vazão, Vitor Francisco, Lino Ferreira, Patrícia R. Pitrez, Lara Carvalho, Akhilesh Rai, Josephine Blersch, Leonor Saúde, Mário Grãos, Inês Honório, Luís M.B.B. Estronca, Xavier Nissan, Ulrich Simon |
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| Přispěvatelé: | Repositório da Universidade de Lisboa |
| Rok vydání: | 2021 |
| Předmět: |
Male
Adolescent Induced Pluripotent Stem Cells 02 engineering and technology Regenerative medicine Glycocalyx 03 medical and health sciences Vasculogenesis Lab-On-A-Chip Devices Toxicity Tests Animals Humans General Materials Science Cytotoxicity Induced pluripotent stem cell Zebrafish 030304 developmental biology 0303 health sciences Matrigel biology Chemistry Endothelial Cells 021001 nanoscience & nanotechnology biology.organism_classification In vitro 3. Good health Cell biology Blood Vessels Nanoparticles Female 0210 nano-technology |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| ISSN: | 2055-6764 2055-6756 |
| DOI: | 10.1039/d0nh00550a |
| Popis: | © The Royal Society of Chemistry, 2021. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported (CC BY-NC 3.0) The vascular bioactivity/safety of nanomaterials is typically evaluated by animal testing, which is of low throughput and does not account for biological differences between animals and humans such as ageing, metabolism and disease profiles. The development of personalized human in vitro platforms to evaluate the interaction of nanomaterials with the vascular system would be important for both therapeutic and regenerative medicine. A library of 30 nanoparticle (NP) formulations, in use in imaging, antimicrobial and pharmaceutical applications, was evaluated in a reporter zebrafish model of vasculogenesis and then tested in personalized humanized models composed of human-induced pluripotent stem cell (hiPSC)-derived endothelial cells (ECs) with ‘‘young’’ and ‘‘aged’’ phenotypes in 3 vascular network formats: 2D (in polystyrene dish), 3D (in Matrigel) and in a blood vessel on a chip. As a proof of concept, vascular toxicity was used as the main readout. The results show that the toxicity profile of NPs to hiPSC-ECs was dependent on the ‘‘age’’ of the endothelial cells and vascular network format. hiPSC-ECs were less susceptible to the cytotoxicity effect of NPs when cultured in flow than in static conditions, the protective effect being mediated, at least in part, by glycocalyx. Overall, the results presented here highlight the relevance of in vitro hiPSC-derived vascular systems to screen vascular nanomaterial interactions. This work was funded by FEDER through the Program COMPETE and by Portuguese fund through FCT in the context of the projects PTDC/SAU-TOX/121887/2010, POCI-01-0145-FEDER-029229, POCI-01-0145-FEDER-016390 and POCI-01-0145-FEDER-029414, as well as the European project ERAatUC (ref. 669088). PP wishes to thank FCT for a BD fellowship (SFRH/BD/71042/2010). The iMM Fish Facility was supported by CONGENTO LISBOA-01-0145-FEDER-022170, co-financed by FCT (Portugal) and Lisboa 2020, under the PORTUGAL 2020 agreement (European Regional Development Fund). The authors have no conflict of interest to disclose. |
| Databáze: | OpenAIRE |
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