PMID- 32824247
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2079-4991 (Print)
IS  - 2079-4991 (Electronic)
IS  - 2079-4991 (Linking)
VI  - 10
IP  - 8
DP  - 2020 Aug 15
TI  - Developmental Neurotoxicity Screening for Nanoparticles Using Neuron-Like Cells 
      of Human Umbilical Cord Mesenchymal Stem Cells: Example with Magnetite 
      Nanoparticles.
LID - 10.3390/nano10081607 [doi]
LID - 1607
AB  - Metallic nanoparticles (NPs), as iron oxide NPs, accumulate in organs, cross the 
      blood-brain barrier and placenta, and have the potential to elicit developmental 
      neurotoxicity (DNT). Human stem cell-derived in vitro models may provide more 
      realistic platforms to study NPs effects on neural cells, and to obtain relevant 
      information on the potential for early or late DNT effects in humans. Primary 
      neuronal-like cells (hNLCs) were generated from mesenchymal stem cells derived 
      from human umbilical cord lining and the effects caused by magnetite 
      (Fe(3)O(4)NPs, 1-50 mug/mL) evaluated. Neuronal differentiation process was 
      divided into stages: undifferentiated, early, mid- and fully-differentiated (from 
      day-2 to 8 of induction) based on different neuronal markers and morphological 
      changes over time. Reduction in neuronal differentiation induction after NP 
      exposure was observed associated with NP uptake: beta-tubulin III (beta-Tub III), 
      microtubule-associated protein 2 (MAP-2), enolase (NSE) and nestin were 
      downregulated (10-40%), starting from 25 mug/mL at the early stage. Effects were 
      exacerbated at higher concentrations and persisted up to 8 days without cell 
      morphology alterations. Adenosine triphosphate (ATP) and caspase-3/7 activity 
      data indicated Fe(3)O(4)NPs-induced cell mortality in a concentration-dependent 
      manner and increases of apoptosis: effects appeared early (from day-3), started 
      at low concentrations (>/=5 mug/mL) and persisted. This new human cell-based model 
      allows different stages of hNLCs to be cultured, exposed to NPs/chemicals, and 
      analyzed for different endpoints at early or later developmental stage.
FAU - Coccini, Teresa
AU  - Coccini T
AD  - Toxicology Unit, Laboratory of Clinical and Experimental Toxicology, Istituti 
      Clinici Scientifici Maugeri IRCCS, Via Maugeri 10, 27100 Pavia, Italy.
FAU - Pignatti, Patrizia
AU  - Pignatti P
AD  - Allergy and Immunology Unit, Istituti Clinici Scientifici Maugeri IRCCS, Via 
      Maugeri 10, 27100 Pavia, Italy.
FAU - Spinillo, Arsenio
AU  - Spinillo A
AD  - Department of Obstetrics and Gynecology, Fondazione IRCCS Policlinico San Matteo 
      and University of Pavia, 27100 Pavia, Italy.
FAU - De Simone, Uliana
AU  - De Simone U
AUID- ORCID: 0000-0002-8423-2954
AD  - Toxicology Unit, Laboratory of Clinical and Experimental Toxicology, Istituti 
      Clinici Scientifici Maugeri IRCCS, Via Maugeri 10, 27100 Pavia, Italy.
LA  - eng
PT  - Journal Article
DEP - 20200815
PL  - Switzerland
TA  - Nanomaterials (Basel)
JT  - Nanomaterials (Basel, Switzerland)
JID - 101610216
PMC - PMC7466682
OTO - NOTNLM
OT  - Fe3O4 nanoparticles
OT  - human primary cell culture
OT  - neurotoxicity
OT  - occupational and environmental exposure
OT  - predictive nanotoxicology
OT  - risk assessment
COIS- The authors declare that they have no conflict of interests.
EDAT- 2020/08/23 06:00
MHDA- 2020/08/23 06:01
PMCR- 2020/08/15
CRDT- 2020/08/23 06:00
PHST- 2020/07/13 00:00 [received]
PHST- 2020/08/10 00:00 [revised]
PHST- 2020/08/12 00:00 [accepted]
PHST- 2020/08/23 06:00 [entrez]
PHST- 2020/08/23 06:00 [pubmed]
PHST- 2020/08/23 06:01 [medline]
PHST- 2020/08/15 00:00 [pmc-release]
AID - nano10081607 [pii]
AID - nanomaterials-10-01607 [pii]
AID - 10.3390/nano10081607 [doi]
PST - epublish
SO  - Nanomaterials (Basel). 2020 Aug 15;10(8):1607. doi: 10.3390/nano10081607.