Human Umbilical Cord Mesenchymal Stem Cell-Based in vitro Model for Neurotoxicity Testing

Area of Science:

• Toxicology and Pharmacology
• Stem Cell Biology
• Neuroscience

Background:

• Current neurotoxicity (NT) testing relies on animal models, which are costly and time-consuming.
• There is a need for alternative in vitro methods for rapid chemical screening and mechanism of action studies.
• Human cell-based systems are preferred for toxicity testing to reduce extrapolation uncertainty from animal models.

Purpose of the Study:

• To describe a step-by-step procedure for using human umbilical cord-derived mesenchymal stem/stromal cells (hMSCs) for in vitro neurotoxicity testing.
• To establish a reliable human cell-based model for assessing the neurotoxic potential of chemicals.
• To provide a protocol that supports the advancement of neurotoxicity research and regulatory decision-making.

Main Methods:

• Isolation, amplification, and storage of hMSCs from human umbilical cord lining membrane.
• Transdifferentiation of hMSCs into neuron-like cells (hNLCs).
• Neurotoxicity assessment of hNLCs using standard cytotoxicity assays after exposure to test compounds.

Main Results:

• Successfully isolated and maintained hMSCs from umbilical cord tissue.
• Efficiently differentiated hMSCs into neuron-like cells (hNLCs).
• Demonstrated the utility of hNLCs in standard in vitro neurotoxicity assays.

Conclusions:

• The described protocol provides a viable alternative system for generating primary human neuron-like cells for neurotoxicity testing.
• This human cell-based approach can aid in more accurate and ethical assessment of chemical neurotoxicity.
• The protocol aligns with current guidelines for using human cell-based systems in toxicity testing.