Gadolinium induced effects on mammalian cell motility, adherence and chromatin structure

Nagy, Gábor; Baksa, Viktória; Kiss, Alexandra; Bánfalvi, Gáspár

doi:10.1007/s10495-016-1311-9

Cited by 8 publications

(7 citation statements)

References 35 publications

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“…In our current space study, we used chondrospheres that are capable of maintaining their viability in a state of hypoxia for a rather long time as well as the ability to produce ECM components ( 28 , 44 ). It is also crucial that chondrocytes are very resistant to stress caused by microgravity (actual or simulated) ( 26 , 45 ). Alternative approaches such as fabricating tissue spheroids from cell monolayers labeled with magnetic nanoparticles ( 46 ) or spontaneous formation of tissue spheroids from monolayer in space ( 40 ) currently do not provide a sufficient number of tissue spheroids with standard size and shape for reproducible experiments.…”

Section: Discussionmentioning

confidence: 99%

“…The main reason for us to make the described experiment in space was the assumption that microgravity would give us the possibility to perform magnetic levitation at a low, nontoxic concentration of paramagnetic Gd 3+ -chelates in comparison with ground conditions. Tissue spheroids are rather large and heavy biological objects, so at a preliminary stage of the current study, we faced a dilemma—using paramagnetic medium, from one side, is critically important for enabling magnetic levitation; from another side, the toxic effects of Gd 3+ are well known and were previously reported ( 26 , 27 , 45 ). According to our previous TEM analysis, 50 mM gadobutrol provides effective magnetic levitation of chondrospheres in a laboratory setup on Earth but causes changes in cellular ultrastructure: margination of nuclear chromatin, swelling of mitochondria and endoplasmic reticulum, accumulation of phagosome, and multiple membrane vacuoles, which are considered as Gd 3+ -induced intracellular dystrophy ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

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Magnetic levitational bioassembly of 3D tissue construct in space

et al. 2020

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Magnetic levitational bioassembly of three-dimensional (3D) tissue constructs represents a rapidly emerging scaffold- and label-free approach and alternative conceptual advance in tissue engineering. The magnetic bioassembler has been designed, developed, and certified for life space research. To the best of our knowledge, 3D tissue constructs have been biofabricated for the first time in space under microgravity from tissue spheroids consisting of human chondrocytes. Bioassembly and sequential tissue spheroid fusion presented a good agreement with developed predictive mathematical models and computer simulations. Tissue constructs demonstrated good viability and advanced stages of tissue spheroid fusion process. Thus, our data strongly suggest that scaffold-free formative biofabrication using magnetic fields is a feasible alternative to traditional scaffold-based approaches, hinting a new perspective avenue of research that could significantly advance tissue engineering. Magnetic levitational bioassembly in space can also advance space life science and space regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Magnetic levitational bioassembly of 3D tissue construct in space

et al. 2020

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“…This feature has led to the development of various gadolinium-based contrast agents [1]. Despite the relatively high biological tolerance (median lethal dose (LD 50 ) of about 100–200 mg/kg), gadolinium is known to interfere with many biological processes [2,3,4]. Three decades of widespread use of gadolinium-based contrast agents increased our knowledge about Gd 3+ -related toxicity.…”

Section: Introductionmentioning

confidence: 99%

Toxicity Mechanism of Low Doses of NaGdF4:Yb3+,Er3+ Upconverting Nanoparticles in Activated Macrophage Cell Lines

et al. 2019

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Gadolinium-doped nanoparticles (NPs) are regarded as promising luminescent probes. In this report, we studied details of toxicity mechanism of low doses of NaGdF4-based fluorescent nanoparticles in activated RAW264.7, J774A.1 macrophages. These cell lines were specifically sensitive to the treatment with nanoparticles. Using nanoparticles of three different sizes, but with a uniform zeta potential (about −11 mV), we observed rapid uptake of NPs by the cells, resulting in the increased lysosomal compartment and subsequent superoxide induction along with a decrease in mitochondrial potential, indicating the impairment of mitochondrial homeostasis. At the molecular level, this led to upregulation of proapoptotic Bax and downregulation of anti-apoptotic Bcl-2, which triggered the apoptosis with phosphatidylserine externalization, caspase-3 activation and DNA fragmentation. We provide a time frame of the toxicity process by presenting data from different time points. These effects were present regardless of the size of nanoparticles. Moreover, despite the stability of NaGdF4 nanoparticles at low pH, we identified cell acidification as an essential prerequisite of cytotoxic reaction using acidification inhibitors (NH4Cl or Bafilomycin A1). Therefore, approaching the evaluation of the biocompatibility of such materials, one should keep in mind that toxicity could be revealed only in specific cells. On the other hand, designing gadolinium-doped NPs with increased resistance to harsh conditions of activated macrophage phagolysosomes should prevent NP decomposition, concurrent gadolinium release, and thus the elimination of its toxicity.

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“…(iii) The third aspect was dealing with gadolinium induced effect on the motility, adherence, and chromatin structure on mammalian cells including HuLi cells. Gadolinium complexes, endocytosed by macrophages and distributed to nuclei, cause apoptosis of macrophages preventing the regeneration of corneal damages [50].…”

Section: Discussionmentioning

confidence: 99%

Reepithelization of the Damaged Cornea in the Presence of Multi-Walled Carbon Nanotubes

Baksa¹,

Kiss²,

Tálas³

et al. 2023

Preprint

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We have established earlier a cell line from the human limbal area to study cell growth and response to the toxic effects of antibiotics used in ophthalmology. In the recent work, the effect of multi-walled carbon nanotubes (MWCNTs) in cornea damage was investigated in vitro and in vivo in mice. In the in vitro experiments, the physiological effects of multi-walled carbon nano-tube (MWCNT) bundles on corneal wound healing were mimicked in vitro by a reepithelization limbal stem cell model. Murine in vivo experiments were performed with intact, non-functionalized MWCNTs to confirm the validity of in vitro tests. The MWCNTs of 10 -30 nm outer diameter at low concentration (5 µg/ml) did not interfere with the wound healing of the damaged limbal cell monolayer. Higher than 50 µg/ml concentrations: a) generated MWCNT aggregates, b) restrained the movement and prolonged the time of wound healing, c) increased the amplitudes of the oscillations of the cells, and d) resulted in scar formation affecting both cor-neal function and refraction. Chromatin condensation, a sensitive test of the viability of cells, including limbal stem cells revealed that the presence of a low concentration of nanotubes (5 µg/ml), did not significantly affect the viability of limbal cells. Chromatin condensation was completed and metaphase chromosomes were seen at higher MWCNT concentration proving that their aggregates did not affect the viability of limbal cells. This concentration of MWCNTs (5 µg/ml) did impact neither the reepithelization in vitro nor in vivo in the scratched eyes of mice. Scar formation took place at higher than 50 µg/ml concentrations and the healing of the cornea was prevented by the lack of movement of increasingly larger macroaggregates. In vivo murine experiments vali-dated in vitro monolayer regrowth followed by time-lapse microscopy portraying realistically the reepithelization of the damaged cornea that process was gradually slowed down by macro aggregate formation and caused the scarring of the cornea.

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Gadolinium induced effects on mammalian cell motility, adherence and chromatin structure

Cited by 8 publications

References 35 publications

Magnetic levitational bioassembly of 3D tissue construct in space

Magnetic levitational bioassembly of 3D tissue construct in space

Toxicity Mechanism of Low Doses of NaGdF4:Yb3+,Er3+ Upconverting Nanoparticles in Activated Macrophage Cell Lines

Reepithelization of the Damaged Cornea in the Presence of Multi-Walled Carbon Nanotubes

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