Science and Research

Transferability and reproducibility of exposed air-liquid interface co-culture lung models

BACKGROUND: The establishment of reliable and robust in vitro models for hazard assessment, a prerequisite for moving away from animal testing, requires the evaluation of model transferability and reproducibility. Lung models that can be exposed via the air, by means of an air-liquid interface (ALI) are promising in vitro models for evaluating the safety of nanomaterials (NMs) after inhalation exposure. We performed an inter-laboratory comparison study to evaluate the transferability and reproducibility of a lung model consisting of the human bronchial cell line Calu-3 as a monoculture and, to increase the physiologic relevance of the model, also as a co-culture with macrophages (either derived from the THP-1 monocyte cell line or from human blood monocytes). The lung model was exposed to NMs using the VITROCELL® Cloud12 system at physiologically relevant dose levels. RESULTS: Overall, the results of the 7 participating laboratories are quite similar. After exposing Calu-3 alone and Calu-3 co-cultures with macrophages, no effects of lipopolysaccharide (LPS), quartz (DQ12) or titanium dioxide (TiO(2)) NM-105 particles on the cell viability and barrier integrity were detected. LPS exposure induced moderate cytokine release in the Calu-3 monoculture, albeit not statistically significant in most labs. In the co-culture models, most laboratories showed that LPS can significantly induce cytokine release (IL-6, IL-8 and TNF-α). The exposure to quartz and TiO(2) particles did not induce a statistically significant increase in cytokine release in both cell models probably due to our relatively low deposited doses, which were inspired by in vivo dose levels. The intra- and inter-laboratory comparison study indicated acceptable interlaboratory variation for cell viability/toxicity (WST-1, LDH) and transepithelial electrical resistance, and relatively high inter-laboratory variation for cytokine production. CONCLUSION: The transferability and reproducibility of a lung co-culture model and its exposure to aerosolized particles at the ALI were evaluated and recommendations were provided for performing inter-laboratory comparison studies. Although the results are promising, optimizations of the lung model (including more sensitive read-outs) and/or selection of higher deposited doses are needed to enhance its predictive value before it may be taken further towards a possible OECD guideline.

  • Braakhuis, H. M.
  • Gremmer, E. R.
  • Bannuscher, A.
  • Drasler, B.
  • Keshavan, S.
  • Rothen-Rutishauser, B.
  • Birk, B.
  • Verlohner, A.
  • Landsiedel, R.
  • Meldrum, K.
  • Doak, S. H.
  • Clift, M. J. D.
  • Erdem, J. S.
  • Foss, O. A. H.
  • Zienolddiny-Narui, S.
  • Serchi, T.
  • Moschini, E.
  • Weber, P.
  • Burla, S.
  • Kumar, P.
  • Schmid, O.
  • Zwart, E.
  • Vermeulen, J. P.
  • Vandebriel, R. J.

Keywords

  • Air exposure
  • Air-liquid interface
  • Inter-laboratory comparison
  • Lung model
  • Nanomaterial
  • Toxicity
Publication details
DOI: 10.1016/j.impact.2023.100466
Journal: NanoImpact
Pages: 100466 
Work Type: Original
Location: CPC-M
Disease Area: COPD, General Lung and Other
Partner / Member: HMGU
Access-Number: 37209722

DZL Engagements

chevron-down