github link
Accession IconGSE75582

Stem cell-derived immature human dorsal root ganglia neurons to identify peripheral neurotoxicants

Organism Icon Homo sapiens
Sample Icon 18 Downloadable Samples
Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Submitter Supplied Information

Description
Safety sciences and the identification chemical hazard have been seen as one of the most immediate practical applications of human pluripotent stem cell technology. Protocols for the generation of many desirable human cell types have been developed, but optimization of neuronal models for toxicological use has been astonishingly slow, and the wide, clinically- important field of peripheral neurotoxicity is still largely unexplored. Here, a 2-step protocol to generate large lots of identical peripheral human neuronal precursors was characterized and adapted to the measurement of peripheral neurotoxicity. High content imaging allowed an unbiased assessment of cell morphology and viability. The computational quantification of neurite growth as functional parameter highly sensitive to disturbances by toxicants was used as endpoint reflecting specific neurotoxicity. The differentiation of cells towards dorsal root ganglia neurons was tracked in relation to a large background data set based on gene expression microarrays. On this basis, a peripheral neurotoxicity (PeriTox) test was developed as first toxicological assay that harnesses the potential of human pluripotent stem cells to generate cell types/tissues that are not otherwise available for prediction of human systemic organ toxicity. Testing of more than 30 chemicals showed that human neurotoxicants, as well as neurite growth enhancers, were correctly identified. Various classes of chemotherapeutics causing human peripheral neuropathies were identified, while they were missed when tested on human central neurons. The PeriTox-test established here shows the potential of human stem cells for clinically-relevant safety testing of drugs in use and of new emerging candidates.
PubMed ID
Total Samples
20
Submitter’s Institution

Samples

Show of 0 Total Samples
Filter
Add/Remove
Accession Code
Title
Sex
Specimen part
Cell line
Processing Information
Additional Metadata
No rows found
Loading...