The influence of bisphenol A on mammalian cell cultivation

Stiefel, Fabian; Paul, Albert Jesuran; Troisi, Jacopo; Sgueglia, Angelo; Stützle, Martina; Herold, Eva Maria; Hesse, Friedemann

doi:10.1007/s00253-015-6956-8

Cited by 7 publications

(7 citation statements)

References 33 publications

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“…These findings might indicate that metals and ceramics demonstrate somewhat more biological inert properties than do plastics. A recent study using cell lines focused on the role of bisphenol A leaching from PC [ 29 ]; it was demonstrated that the metabolic activity of sensitive cell lines can be influenced by bisphenol A. In the present study, we did not observe a significant up-regulation of CTSD in indirect cultures, but did in direct culture of BM-MSCs on PC.…”

Section: Discussioncontrasting

confidence: 70%

Response of Primary Human Bone Marrow Mesenchymal Stromal Cells and Dermal Keratinocytes to Thermal Printer Materials In Vitro

et al. 2016

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Advancement in thermal three-dimensional printing techniques has greatly increased the possible applications of various materials in medical applications and tissue engineering. Yet, potential toxic effects on primary human cells have been rarely investigated. Therefore, we compared four materials commonly used in thermal printing for bioengineering, namely thermally printed acrylonitrile butadiene styrene, MED610, polycarbonate, and polylactic acid, and investigated their effects on primary human adult skin epidermal keratinocytes and bone marrow mesenchymal stromal cells (BM-MSCs) in vitro. We investigated indirect effects on both cell types caused by potential liberation of soluble substances from the materials, and also analyzed BM-MSCs in direct contact with the materials. We found that even in culture without direct contact with the materials, the culture with MED610 (and to a lesser extent acrylonitrile butadiene styrene) significantly affected keratinocytes, reducing cell numbers and proliferation marker Ki67 expression, and increasing glucose consumption, lactate secretion, and expression of differentiation-associated genes. BM-MSCs had decreased metabolic activity, and exhibited increased cell death in direct culture on the materials. MED610 and acrylonitrile butadiene styrene induced the strongest expression of genes associated to differentiation and estrogen receptor activation. In conclusion, we found strong cell-type-specific effects of the materials, suggesting that materials for applications in regenerative medicine should be carefully selected not only based on their mechanical properties but also based on their cell-type-specific biological effects.Electronic supplementary materialThe online version of this article (doi:10.1007/s40846-016-0118-z) contains supplementary material, which is available to authorized users.

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Section: Discussioncontrasting

confidence: 70%

Response of Primary Human Bone Marrow Mesenchymal Stromal Cells and Dermal Keratinocytes to Thermal Printer Materials In Vitro

et al. 2016

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“…BPA is required for polycarbonate plastics and epoxy resin production. A recent study demonstrated that CHO cells cultured in BPA‐free polyethylene terephthalate glycol (PETG) compared to polycarbonate flasks, demonstrated no effects on growth or viability but did play a significant role on cellular metabolism by reducing specific productivity through a less efficient metabolic program …”

Section: Discussionmentioning

confidence: 99%

“…A recent study demonstrated that CHO cells cultured in BPA-free polyethylene terephthalate glycol (PETG) compared to polycarbonate flasks, demonstrated no effects on growth or viability but did play a significant role on cellular metabolism by reducing specific productivity through a less efficient metabolic program. 22 We took two commonly used and available cell lines, CHO-K1 and CHO-DP12, and assessed their sensitivity to various spiked concentrations of bDtBPP. We observed that both cell lines demonstrated sensitivities to different concentrations with 0.035 and 0.1 mg/L inducing a 50% growth inhibition 96 h into culture for the CHO-K1 and CHO-DP12 cells ( Figure 5A,B).…”

Section: Discussionmentioning

confidence: 99%

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Process‐relevant concentrations of the leachable bDtBPP impact negatively on CHO cell production characteristics

Kelly

McSweeney

Coleman

et al. 2016

Biotechnology Progress

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The biopharmaceutical industry has invested considerably in the implementation of single-use disposable bioreactors in place of or in addition to their stainless steel-counterparts. This new wave of construction materials for disposable bioprocess containers encompass a plethora of uncharacterized secondary compounds that, when in contact with the culture media, can leach, contaminating the bioprocess. One such cytotoxic leachable already receiving attention is bis(2,4-di-tert-butylphenyl)-phosphate (bDtBPP), a breakdown product of the secondary antioxidant Irgafos 168 in polyethylene-film based bags. This compound has been demonstrated to inhibit cell growth at concentrations ranging from 0.12 to 0.73 mg/L across an array of cell lines. Here we demonstrate that a further two CHO cell lines exhibit sensitivity to bDtBPP exposure at concentrations lower than that previously reported (0.035-0.1 mg/L). Furthermore, these inhibitory concentrations reflect bDtBPP levels found to leach early into the bioprocess, exposing reactor inoculums to serious risk. Quantitative label-free LC-MS/MS revealed that irrespective of cell line or concentration of bDtBPP, 8 proteins were found to be commonly differentially expressed in response to exposure to the compound highlighting biological processes related to cellular stress. Although the glycoprofile of the recombinant antibody remains primarily unchanged, we demonstrate that this compound when spiked at meaningful concentrations 72 h into culture considerably reduces the maximum cell density achieved. Studies like this reinforce the requirement for the complete characterization of all potential leachable compounds from disposable materials to assess their risk not only to the patient but also to the production pipeline itself. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1547-1558, 2016.

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“…BPA is an estrogenic EDC that binds to different estrogen receptors located in both the nucleus (ERα and ERβ) and the membrane of the cell [2, 3]. This compound is mostly used in the plastic industry with an approximate production of 5x10 9 kg per year [4], and it is the main component in the manufacture of plastic containers and epoxy resins. Therefore, humans are exposed to BPA on a daily basis, with the average diet (food and beverages contaminated by their plastic containers) being the most important source of risk.…”

Section: Introductionmentioning

confidence: 99%

Sex-associated protective effect of early bisphenol-A exposure during enteric infection with Trichinella spiralis in mice

Nava-Castro

Solleiro-Villavicencio

Río-Araiza

et al. 2019

PLoS ONE

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Bisphenol A (BPA) is an endocrine disruptor compound with estrogenic activity, possessing affinity for both nuclear (ERα and ERβ) and membrane estrogen receptors. The main source of BPA exposure comes from the contamination of food and water by plastic storage containers or disposable bottles, among others, in which case BPA is easily ingested. Exposure to BPA during early pregnancy leads to lifelong effects; however, its effect on the immune system has not been fully studied. Since endocrine and immune systems interact in a bidirectional manner, the disruption of the former may cause permanent alterations of the latter, thus affecting a future anti-parasitic response. In this study, neonate BALB/c mice were exposed to a single dose of BPA (250 μg/kg); once sexual maturity was reached, they were orally infected with Trichinella spiralis (T . spiralis) . The analyses performed after 5 days of infection revealed a decreased parasitic load in the duodenum of mice in the BPA-treated group. Flow cytometry analyses also revealed changes in the immune cell subpopulations of the infected animals when compared to the BPA-treated group. RT-PCR analyses of duodenum samples showed an increased expression of TNF-α, IFN-γ, IL-4, IL-5, and IL-9 in the BPA-treated group. These findings show a new aspect whereby early-life exposure to BPA contributes to the protection against T . spiralis by modulating the anti-parasitic immune response.

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The influence of bisphenol A on mammalian cell cultivation

Cited by 7 publications

References 33 publications

Response of Primary Human Bone Marrow Mesenchymal Stromal Cells and Dermal Keratinocytes to Thermal Printer Materials In Vitro

Response of Primary Human Bone Marrow Mesenchymal Stromal Cells and Dermal Keratinocytes to Thermal Printer Materials In Vitro

Process‐relevant concentrations of the leachable bDtBPP impact negatively on CHO cell production characteristics

Sex-associated protective effect of early bisphenol-A exposure during enteric infection with Trichinella spiralis in mice

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