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Hollow Fiber Bioreactors for In Vivo-like Mammalian Tissue Culture
Published on: May 26, 2016
A new in vitro cellular system for the analysis of mineral fiber biopersistence
Hermine Dika Nguea1, Aymon de Reydellet, Patrice Lehuédé
1Laboratoire de Bactériologie Virologie, Faculté de Médecine, Nancy-University, 9 Avenue de la Forêt de Haye, BP 184, 54505, Vandoeuvre-lès-Nancy Cedex, France.
Abstract:
The toxicity of mineral fibers, whether they are natural or man made (MMMF), is usually evaluated in vivo using biopersistence tests in rodents. Development of an in vitro cellular model would be worthwhile in order to reduce, refine and finally replace animal models. For this purpose, we developed an in vitro assay using human monocytic cell line (U-937) to evaluate a new manufactured rock wool fiber (HDN) biodegradation. Experiments on earlier known mineral fibers asbestos (crocidolite) and glass wool fibers (CM44) were also performed. U-937 responded to HDN and CM44 only if they were activated. Among the different activators we used, Escherichia coli living cells as well as FS were the most efficient as evidenced by alterations of HDN and CM44 surface, detected by scanning electron microscopy, and by the measure of silicon released from the rock wool fibers. Asbestos fibers were not degraded when incubated in the presence of living bacteria. The MMMF modifications were function of the fiber composition, the time of exposure to activated cells and the concentration of activators. The pattern of MMMF degradation by our in vitro system was in accordance with those observed in an in vivo study, thus indicating that the fiber degradation by macrophage cells activated by E. coli living cells as well as FS is a valuable system to assess mineral fibers' biopersistence.
Insights
This study developed an in vitro model using activated human cells to assess mineral fiber biodegradation, offering a promising alternative to animal testing for evaluating man-made mineral fibers (MMMF). The system accurately predicted biopersistence, supporting its use in reducing animal use.
Area of Science:
- Biomedical Science
- Materials Science
- Toxicology
Background:
- In vivo biopersistence tests in rodents are standard for evaluating mineral fiber toxicity.
- There is a need for in vitro models to reduce, refine, and replace animal testing.
- Man-made mineral fibers (MMMF) require reliable biodegradation assessment.
Purpose of the Study:
- To develop and validate an in vitro cellular model for assessing the biodegradation of manufactured mineral fibers (MMMF).
- To evaluate the biopersistence of a new rock wool fiber (HDN) and compare it with asbestos and glass wool fibers.
- To establish a system that correlates with in vivo findings for MMMF biopersistence.
Main Methods:
- An in vitro assay using the human monocytic cell line U-937 was developed.
- U-937 cells were activated using Escherichia coli (E. coli) living cells and FS to assess fiber biodegradation.
- Fiber surface alterations (scanning electron microscopy) and silicon release were measured to evaluate degradation.
Main Results:
- U-937 cells, when activated, degraded HDN and CM44 glass wool fibers, but not asbestos.
- E. coli and FS were effective activators, causing significant surface changes and silicon release from HDN and CM44.
- Degradation patterns in the in vitro system aligned with previously observed in vivo results.
Conclusions:
- Activated macrophage cells provide a valuable in vitro system for assessing mineral fiber biopersistence.
- This cellular model, using E. coli or FS activation, can help reduce reliance on animal testing for MMMF safety evaluation.
- The system's ability to mimic in vivo degradation patterns validates its utility in toxicological assessments.

