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Growing knowledge: using stem cells to study developmental neurotoxicity.

Betts KS - Environ. Health Perspect. (2010)

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The other alternative was to “use animals to make the culture every time you want cells. ” Stem cells have the potential to improve how chemicals are evaluated because they involve using human cells, and they may be able to provide a broad range of data on a wide swath of chemicals much more quickly than conventional toxicology testing, Woodruff points out. “It’s a noninvasive technique for humans to test effects on humans,” she says... Stem cells have the added advantage of obviating the need for laboratory animals. “There has been a push to decrease the use of animal testing,” Woodruff says, noting that such a reduction is an explicit goal of the European Union’s Registration, Evaluation, Authorisation and Restriction of Chemical Substances regulatory framework... Using conventional animal-based neurotoxicity screening tests to evaluate the tens of thousands of chemicals for which no neurotoxicity information is available “is just plain impractical,” says Shafer, who is involved in a project using neuroprogenitor cells to evaluate how chemicals may be affecting human neurodevelopment. “The cost would be too great, it would take years and years to accomplish, and. .. it would take literally millions of animals. ” Using human stem cells in toxicology testing can overcome other detriments of animal testing as well... Biologists have long suspected that because of differences between early embryonic development in rodents and humans, animal-based testing may not always be a good predictor of human developmental neurotoxicity, particularly in the earliest stages. “It could be that for some particular pathways [such as the ones mediated by the aryl hydrocarbon receptor (AhR)], there are going to be these species differences,” Woodruff says... Efforts by researchers in Poland and at the U.S. EPA to create tests to assess developmental neurotoxicity using stem or neuroprogenitor cells are looking at similar end points... In order for everything to develop properly, some processes must take place in a certain temporal sequence, whereas others are spatially dependent... If neurons cannot develop in the proper temporal and spatial sequence, or if the sequence is disrupted, the end result can be neurodevelopmental impairment, Shafer says... Most recently, they compared the responses of human and mouse neurospheres to polyaromatic hydrocarbons, whose developmental neurotoxicity is based on activation of the AhR... Fritsche and colleagues found the AhR was not activated in the human test cells and wrote that “an accumulating body of evidence now indicates that human AhR signaling is less operative than AhR function in most laboratory animals. ” Neurospheres have the same weaknesses as other in vitro systems, Fritsche says: “No pharmacokinetics, as we do not have a whole organism, and limited metabolic capacity... In time, they succeeded in devising an uncontroversial source of pluripotent-like stem cells using human umbilical cord blood... From there, team member Leonora Buzanska, who now heads the Stem Cell Bioengineering Laboratory at the academy’s Mossakowski Medical Research Centre, found a way to generate a neural stem cell line... More recently, in collaboration with a research team led by Sandra Coecke of the European Commission Joint Research Centre’s In Vitro Models Unit, Buzanska and her Warsaw colleagues demonstrated this cell line can serve as the model system for developmental neurotoxicity testing... Shafer says his team’s goal is to develop what he calls a “first-tier” approach to identify chemicals that merit more detailed developmental neurotoxicity testing, perhaps following up with an alternative species model such as zebrafish and then a rodent or other mammalian species... At press time it was unclear how the ultimate fate of the August ruling on stem cells would affect projects of some of the researchers interviewed for this article... For instance, Smith is collaborating with Steve Stice, director of the University of Georgia Regenerative Bioscience Center, to develop a way to use “germ-like” cells derived from human embryonic stem cells to produce an in vitro system for investigating the developmental and reproductive effects of compounds that affect endocrine-system functioning.

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Neural stem cell cultureFluorescent light micrograph of a cluster of human neural stem cells shows the cells differentiating into different cell types as they migrate out from the central neurosphere. Lighter blue indicates astroglial fibrillary acidic protein, yellow indicates neuronal tubulin III, and pink indicates nuclear DNA.
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f1-ehp-118-a432: Neural stem cell cultureFluorescent light micrograph of a cluster of human neural stem cells shows the cells differentiating into different cell types as they migrate out from the central neurosphere. Lighter blue indicates astroglial fibrillary acidic protein, yellow indicates neuronal tubulin III, and pink indicates nuclear DNA.


Growing knowledge: using stem cells to study developmental neurotoxicity.

Betts KS - Environ. Health Perspect. (2010)

Neural stem cell cultureFluorescent light micrograph of a cluster of human neural stem cells shows the cells differentiating into different cell types as they migrate out from the central neurosphere. Lighter blue indicates astroglial fibrillary acidic protein, yellow indicates neuronal tubulin III, and pink indicates nuclear DNA.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2957950&req=5

f1-ehp-118-a432: Neural stem cell cultureFluorescent light micrograph of a cluster of human neural stem cells shows the cells differentiating into different cell types as they migrate out from the central neurosphere. Lighter blue indicates astroglial fibrillary acidic protein, yellow indicates neuronal tubulin III, and pink indicates nuclear DNA.

View Article: PubMed Central - PubMed

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

The other alternative was to “use animals to make the culture every time you want cells. ” Stem cells have the potential to improve how chemicals are evaluated because they involve using human cells, and they may be able to provide a broad range of data on a wide swath of chemicals much more quickly than conventional toxicology testing, Woodruff points out. “It’s a noninvasive technique for humans to test effects on humans,” she says... Stem cells have the added advantage of obviating the need for laboratory animals. “There has been a push to decrease the use of animal testing,” Woodruff says, noting that such a reduction is an explicit goal of the European Union’s Registration, Evaluation, Authorisation and Restriction of Chemical Substances regulatory framework... Using conventional animal-based neurotoxicity screening tests to evaluate the tens of thousands of chemicals for which no neurotoxicity information is available “is just plain impractical,” says Shafer, who is involved in a project using neuroprogenitor cells to evaluate how chemicals may be affecting human neurodevelopment. “The cost would be too great, it would take years and years to accomplish, and. .. it would take literally millions of animals. ” Using human stem cells in toxicology testing can overcome other detriments of animal testing as well... Biologists have long suspected that because of differences between early embryonic development in rodents and humans, animal-based testing may not always be a good predictor of human developmental neurotoxicity, particularly in the earliest stages. “It could be that for some particular pathways [such as the ones mediated by the aryl hydrocarbon receptor (AhR)], there are going to be these species differences,” Woodruff says... Efforts by researchers in Poland and at the U.S. EPA to create tests to assess developmental neurotoxicity using stem or neuroprogenitor cells are looking at similar end points... In order for everything to develop properly, some processes must take place in a certain temporal sequence, whereas others are spatially dependent... If neurons cannot develop in the proper temporal and spatial sequence, or if the sequence is disrupted, the end result can be neurodevelopmental impairment, Shafer says... Most recently, they compared the responses of human and mouse neurospheres to polyaromatic hydrocarbons, whose developmental neurotoxicity is based on activation of the AhR... Fritsche and colleagues found the AhR was not activated in the human test cells and wrote that “an accumulating body of evidence now indicates that human AhR signaling is less operative than AhR function in most laboratory animals. ” Neurospheres have the same weaknesses as other in vitro systems, Fritsche says: “No pharmacokinetics, as we do not have a whole organism, and limited metabolic capacity... In time, they succeeded in devising an uncontroversial source of pluripotent-like stem cells using human umbilical cord blood... From there, team member Leonora Buzanska, who now heads the Stem Cell Bioengineering Laboratory at the academy’s Mossakowski Medical Research Centre, found a way to generate a neural stem cell line... More recently, in collaboration with a research team led by Sandra Coecke of the European Commission Joint Research Centre’s In Vitro Models Unit, Buzanska and her Warsaw colleagues demonstrated this cell line can serve as the model system for developmental neurotoxicity testing... Shafer says his team’s goal is to develop what he calls a “first-tier” approach to identify chemicals that merit more detailed developmental neurotoxicity testing, perhaps following up with an alternative species model such as zebrafish and then a rodent or other mammalian species... At press time it was unclear how the ultimate fate of the August ruling on stem cells would affect projects of some of the researchers interviewed for this article... For instance, Smith is collaborating with Steve Stice, director of the University of Georgia Regenerative Bioscience Center, to develop a way to use “germ-like” cells derived from human embryonic stem cells to produce an in vitro system for investigating the developmental and reproductive effects of compounds that affect endocrine-system functioning.

Show MeSH