In vitro toxicity screening of magnetite nanoparticles by applying mesenchymal stem cells derived from human umbilical cord lining

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Despite the growing interest in nanoparticles (NPs), their toxicity has not yet been defined and the development of new strategies and predictive models are required. Human stem cells (SCs) offer a promising and innovative cell-based model. Among SCs, mesenchymal SCs (MSCs) derived from cord lining membrane (CL) may represent a new species-specific tool for establishing efficient platforms for primary screening and toxicity/safety testing of NPs. Superparamagnetic iron oxide NPs, including magnetite (Fe3O4NPs), have aroused great public health and scientific concerns despite their extensive uses. In this study, CL-MSCs were characterized and applied for in vitro toxicity screening of Fe3O4NPs. Cytotoxicity, internalization/uptake, differentiation and proliferative capacity were evaluated after exposure to different Fe3O4NP concentrations. Data were compared with those obtained from bone marrow (BM)-MSCs. We observed, at early passages (P3), that: (1) cytotoxicity occurred at 10 μg/mL in CL-MSCs and 100 μg/mL in BM-MSCs (no differences in toxicity, between CL- and BM-MSCs, were observed at higher dosage, 100-300 μg/mL); (2) cell density decrease and monolayer features loss were affected at ≥50 μg/mL in CL-MSCs only; and (3) NP uptake was concentration-dependent in both MSCs. After 100 μg/mL Fe3O4NP exposures, the capacity of proliferation was decreased (P5-P9) in CL-MSCs without morphology alteration. Moreover, a progressive decrease of intracellular Fe3O4NPs was observed over culture time. Antigen surface expression and multilineage differentiation were not influenced. These findings suggest that CL-MSCs could be used as a reliable cell-based model for Fe3O4NP toxicity screening evaluation and support the use of this approach for improving the confidence degree on the safety of NPs to predict health outcomes.

Original languageEnglish
JournalJournal of Applied Toxicology
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Magnetite Nanoparticles
Umbilical Cord
Stem cells
Mesenchymal Stromal Cells
Linings
Toxicity
Screening
Membranes
Nanoparticles
Bone
Bone Marrow
Cytotoxicity
Stem Cells
Safety testing
Magnetite nanoparticles
Safety
Public health
Surface Antigens
In Vitro Techniques
Monolayers

Keywords

  • bone marrow
  • environmental and occupational exposure
  • human cell model
  • in vitro
  • mesenchymal stem cells
  • risk assessment
  • toxicity
  • umbilical cord lining

ASJC Scopus subject areas

  • Toxicology

Cite this

@article{b47c932bc3314823b2097d72d2232931,
title = "In vitro toxicity screening of magnetite nanoparticles by applying mesenchymal stem cells derived from human umbilical cord lining",
abstract = "Despite the growing interest in nanoparticles (NPs), their toxicity has not yet been defined and the development of new strategies and predictive models are required. Human stem cells (SCs) offer a promising and innovative cell-based model. Among SCs, mesenchymal SCs (MSCs) derived from cord lining membrane (CL) may represent a new species-specific tool for establishing efficient platforms for primary screening and toxicity/safety testing of NPs. Superparamagnetic iron oxide NPs, including magnetite (Fe3O4NPs), have aroused great public health and scientific concerns despite their extensive uses. In this study, CL-MSCs were characterized and applied for in vitro toxicity screening of Fe3O4NPs. Cytotoxicity, internalization/uptake, differentiation and proliferative capacity were evaluated after exposure to different Fe3O4NP concentrations. Data were compared with those obtained from bone marrow (BM)-MSCs. We observed, at early passages (P3), that: (1) cytotoxicity occurred at 10 μg/mL in CL-MSCs and 100 μg/mL in BM-MSCs (no differences in toxicity, between CL- and BM-MSCs, were observed at higher dosage, 100-300 μg/mL); (2) cell density decrease and monolayer features loss were affected at ≥50 μg/mL in CL-MSCs only; and (3) NP uptake was concentration-dependent in both MSCs. After 100 μg/mL Fe3O4NP exposures, the capacity of proliferation was decreased (P5-P9) in CL-MSCs without morphology alteration. Moreover, a progressive decrease of intracellular Fe3O4NPs was observed over culture time. Antigen surface expression and multilineage differentiation were not influenced. These findings suggest that CL-MSCs could be used as a reliable cell-based model for Fe3O4NP toxicity screening evaluation and support the use of this approach for improving the confidence degree on the safety of NPs to predict health outcomes.",
keywords = "bone marrow, environmental and occupational exposure, human cell model, in vitro, mesenchymal stem cells, risk assessment, toxicity, umbilical cord lining",
author = "Teresa Coccini and {De Simone}, Uliana and Marianna Roccio and Stefania Croce and Elisa Lenta and Marco Zecca and Arsenio Spinillo and Avanzini, {Maria Antonietta}",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/jat.3819",
language = "English",
journal = "Journal of Applied Toxicology",
issn = "0260-437X",
publisher = "John Wiley and Sons Ltd",

}

TY - JOUR

T1 - In vitro toxicity screening of magnetite nanoparticles by applying mesenchymal stem cells derived from human umbilical cord lining

AU - Coccini, Teresa

AU - De Simone, Uliana

AU - Roccio, Marianna

AU - Croce, Stefania

AU - Lenta, Elisa

AU - Zecca, Marco

AU - Spinillo, Arsenio

AU - Avanzini, Maria Antonietta

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Despite the growing interest in nanoparticles (NPs), their toxicity has not yet been defined and the development of new strategies and predictive models are required. Human stem cells (SCs) offer a promising and innovative cell-based model. Among SCs, mesenchymal SCs (MSCs) derived from cord lining membrane (CL) may represent a new species-specific tool for establishing efficient platforms for primary screening and toxicity/safety testing of NPs. Superparamagnetic iron oxide NPs, including magnetite (Fe3O4NPs), have aroused great public health and scientific concerns despite their extensive uses. In this study, CL-MSCs were characterized and applied for in vitro toxicity screening of Fe3O4NPs. Cytotoxicity, internalization/uptake, differentiation and proliferative capacity were evaluated after exposure to different Fe3O4NP concentrations. Data were compared with those obtained from bone marrow (BM)-MSCs. We observed, at early passages (P3), that: (1) cytotoxicity occurred at 10 μg/mL in CL-MSCs and 100 μg/mL in BM-MSCs (no differences in toxicity, between CL- and BM-MSCs, were observed at higher dosage, 100-300 μg/mL); (2) cell density decrease and monolayer features loss were affected at ≥50 μg/mL in CL-MSCs only; and (3) NP uptake was concentration-dependent in both MSCs. After 100 μg/mL Fe3O4NP exposures, the capacity of proliferation was decreased (P5-P9) in CL-MSCs without morphology alteration. Moreover, a progressive decrease of intracellular Fe3O4NPs was observed over culture time. Antigen surface expression and multilineage differentiation were not influenced. These findings suggest that CL-MSCs could be used as a reliable cell-based model for Fe3O4NP toxicity screening evaluation and support the use of this approach for improving the confidence degree on the safety of NPs to predict health outcomes.

AB - Despite the growing interest in nanoparticles (NPs), their toxicity has not yet been defined and the development of new strategies and predictive models are required. Human stem cells (SCs) offer a promising and innovative cell-based model. Among SCs, mesenchymal SCs (MSCs) derived from cord lining membrane (CL) may represent a new species-specific tool for establishing efficient platforms for primary screening and toxicity/safety testing of NPs. Superparamagnetic iron oxide NPs, including magnetite (Fe3O4NPs), have aroused great public health and scientific concerns despite their extensive uses. In this study, CL-MSCs were characterized and applied for in vitro toxicity screening of Fe3O4NPs. Cytotoxicity, internalization/uptake, differentiation and proliferative capacity were evaluated after exposure to different Fe3O4NP concentrations. Data were compared with those obtained from bone marrow (BM)-MSCs. We observed, at early passages (P3), that: (1) cytotoxicity occurred at 10 μg/mL in CL-MSCs and 100 μg/mL in BM-MSCs (no differences in toxicity, between CL- and BM-MSCs, were observed at higher dosage, 100-300 μg/mL); (2) cell density decrease and monolayer features loss were affected at ≥50 μg/mL in CL-MSCs only; and (3) NP uptake was concentration-dependent in both MSCs. After 100 μg/mL Fe3O4NP exposures, the capacity of proliferation was decreased (P5-P9) in CL-MSCs without morphology alteration. Moreover, a progressive decrease of intracellular Fe3O4NPs was observed over culture time. Antigen surface expression and multilineage differentiation were not influenced. These findings suggest that CL-MSCs could be used as a reliable cell-based model for Fe3O4NP toxicity screening evaluation and support the use of this approach for improving the confidence degree on the safety of NPs to predict health outcomes.

KW - bone marrow

KW - environmental and occupational exposure

KW - human cell model

KW - in vitro

KW - mesenchymal stem cells

KW - risk assessment

KW - toxicity

KW - umbilical cord lining

UR - http://www.scopus.com/inward/record.url?scp=85067435495&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067435495&partnerID=8YFLogxK

U2 - 10.1002/jat.3819

DO - 10.1002/jat.3819

M3 - Article

AN - SCOPUS:85067435495

JO - Journal of Applied Toxicology

JF - Journal of Applied Toxicology

SN - 0260-437X

ER -