Thyroid method 8b: Proliferation, migration and oligodendrocyte maturation (including myelin formation) in mixed neuronal/glial culture (neurospheres) derived from human induced Pluripotent Stem Cells (hiPSC)

Topic: Endocrine disruption

Test Method Number:

TM2019-18 (EU)

Short Name of TM:

PMOD-hNPC

Year received:

2019

Responsible Organisation:

EURL ECVAM - European Union

General Comments:

Method Description

Thyroid hormone disruption can interfere with proliferation, migration and differentiation of oligodendrocyte which may lead to neurodevelopmental impairments. The method encompasses evaluation of these biological processes using mixed neuronal/glial culture derived from human induced Pluripotent Stem Cells (hiPSC) cultured as free-floating neurospheres. Cell viability, proliferation, migration and differentiation measured by expression of myelin specific proteins are assessed following a 1-2-week treatment with test items.

This method was selected with other methods to assess modulating effects on the thyroid system (OECD, 2014). Information on these selected methods is available in TSAR as ‘Thyroid methods’.

Track Approval Status

Submission
Validation
Peer-review
Recommendation
Regulatory acceptance/Standards

Submission

Show status

Date	Stage	Comment	Documents/Links
Jun 2017	Assessment of presubmission	Selection of the test method for the Thyroid Validation Study based on the OECD scoping document on 'in vitro and ex vivo methods for the identification of modulators of thyroid hormone signalling' and guidance from the Endocrine Disrupters Testing and Assessment Advisory Group considering scientific advances since the issuing of the OECD scoping document, human relevance, possibility for High Throughput screening and availability of method elements (such as reagents and detection method) to a wide range of future users.	OECD scoping document (OECD, 2014)OECD detailed review paper (OECD, 2012)OECD Endocrine Disrupters Testing and Assessment Advisory Group
Sep 2019	Assessment of full submission	It was decided that the human neural progenitor cells of the original method cannot be used for ethical considerations and the alternative method using human induced pluripotent stem cells needs further standardisation. Further evaluation of the method is pending the availability of a standardised test system. OECD Good In Vitro Method Practices (GIVIMP, OECD, 2018) has been used as guidance.	OECD Good In Vitro Method Practices (GIVIMP, OECD, 2018)

Validation

Peer-review

Recommendation

Regulatory acceptance/Standards