Induced pluripotent stem cell-derived vascular networks to screen nano–bio interactions

Nanoscale Horizons, vol. 6, pp. 245–259

Abstract

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.

Authors 13

1. Luı́s M.B.B. Estronca

   University of Coimbra

   Affiliation as printed

   Coimbra

   Faculty of Medicine

   Portugal

   University of Coimbra

   Faculty of Medicine, University of Coimbra, Coimbra, Portugal

2. Vítor Francisco

   University of Coimbra · Centro de Neurociências e Biologia Celular

   Affiliation as printed

   Center for Neuroscience and Cell Biology

   Coimbra

   Portugal

   University of Coimbra

   Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

3. Patrícia R. Pitrez

   University of Coimbra · Centro de Neurociências e Biologia Celular

   Affiliation as printed

   Center for Neuroscience and Cell Biology

   Coimbra

   Portugal

   University of Coimbra

   Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

4. Inês Agapito Honório

   University of Coimbra · Centro de Neurociências e Biologia Celular

   Affiliation as printed

   Center for Neuroscience and Cell Biology

   Coimbra

   Portugal

   University of Coimbra

   Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

5. Lara Carvalho

   University of Lisbon · Instituto de Medicina Molecular João Lobo Antunes · Instituto de Histologia e Biologia do Desenvolvimento

   Affiliation as printed

   Faculdade de Medicina da Universidade de Lisboa

   Instituto de Medicina Molecular e Instituto de Histologia e Biologia do Desenvolvimento

   Lisboa

   Portugal

   Instituto de Medicina Molecular e Instituto de Histologia e Biologia do Desenvolvimento, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal

6. Helena Vazão

   University of Coimbra · Centro de Neurociências e Biologia Celular

   Affiliation as printed

   Center for Neuroscience and Cell Biology

   Coimbra

   Portugal

   University of Coimbra

   Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

7. Josephine Blersch

   University of Coimbra · Centro de Neurociências e Biologia Celular

   Affiliation as printed

   Center for Neuroscience and Cell Biology

   Coimbra

   Portugal

   University of Coimbra

   Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

8. Akhilesh Rai

   University of Coimbra

   Affiliation as printed

   Coimbra

   Faculty of Medicine

   Portugal

   University of Coimbra

   Faculty of Medicine, University of Coimbra, Coimbra, Portugal

9. Xavier Nissan

   Association Francaise contre les Myopathies · Evry (Norway) · Institut des Cellules Souches pour le Traitement et l'Étude des Maladies Monogéniques

   Affiliation as printed

   AFM

   CECS

   Evry cedex

   I-STEM

   Institute for Stem Cell Therapy and Exploration of Monogenic diseases

   CECS, I-STEM, AFM, Institute for Stem Cell Therapy and Exploration of Monogenic diseases, Evry cedex, France

10. Ulrich Simon Aachen Institute of Inorganic Chemistry

    RWTH Aachen University

    Affiliation as printed

    Germany

    Institute of Inorganic Chemistry

    RWTH Aachen University

    Institute of Inorganic Chemistry, RWTH Aachen University, Germany

11. Mário Grãos

    University of Coimbra · Centro de Neurociências e Biologia Celular

    Affiliation as printed

    Center for Neuroscience and Cell Biology

    Coimbra

    Portugal

    University of Coimbra

    Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

12. Leonor Saúde

    University of Lisbon · Instituto de Medicina Molecular João Lobo Antunes · Instituto de Histologia e Biologia do Desenvolvimento

    Affiliation as printed

    Faculdade de Medicina da Universidade de Lisboa

    Instituto de Medicina Molecular e Instituto de Histologia e Biologia do Desenvolvimento

    Lisboa

    Portugal

    Instituto de Medicina Molecular e Instituto de Histologia e Biologia do Desenvolvimento, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal

13. Lino Ferreira corresponding

    University of Coimbra

    Affiliation as printed

    Coimbra

    Faculty of Medicine

    Portugal

    University of Coimbra

    Faculty of Medicine, University of Coimbra, Coimbra, Portugal