Embryo model resembles the early stages of the complete human central nervous system

Human pluripotent stem cells (hPSCs) have been used to create a complete model of the human central nervous system and mirror its early stages of development in vitro.

Using microfluidic gradients, researchers at the University of Michigan, the Weizmann Institute of Science in Israel, and the University of Pennsylvania have developed the first model to replicate the complex patterning of the neural tube – the critical structure that develops into the brain and spinal cord – opening avenues into understanding neurodevelopmental disorders.

'Models like this will open doors for fundamental research to understand early development of the human central nervous system and how it could go wrong in different disorders,' said Jianping Fu, professor of medical engineering from the University of Michigan and corresponding author of the study published in Nature.

Previously, stem-cell-based embryo models (SCBEMs) were only able to model one part of the nervous system (see BioNews 1177). This new model is shown to simultaneously develop all three sections of the embryonic brain and spinal cord.

Stem cells roughly the size of the neural tube were exposed to specific gradients of signalling molecules to induce patterning responses similar to those seen in embryonic development.

Over 40 days, this allowed the cells to progress into specialised cell types and form the main structures seen in early embryonic development: the forebrain, hindbrain and midbrain. The development continued for 11 weeks post-fertilisation to allow the researchers to understand which genes and signalling pathways were involved in cell differentiation.

The authors believe that this SCBEM has the potential to advance tissue engineering techniques for therapeutic intervention and regenerative medicine. Co-author and neuroscientist from the University of Pennsylvania, Dr Guo-Li Ming emphasised the potential application of their research: 'We try to understand not only the basic biology of human brain development, but also diseases – why we have brain-related diseases, their pathology, and how we can come up with effective strategies to treat them.'

The team is planning to use the model to develop organoids using patient-derived stem cells in order to study different human brain diseases. They hope that organoids developed in this way may be used for identifying which drugs offer the most successful treatment.

Although the model has many advantages, it is not without limitations. Currently, it cannot replicate conditions resulting from abnormal neural tube closure, such as spina bifida. The model also does not have peripheral nerves or functional neuronal circuitry, which are required to process experiences and create neural pathways.

Dr Insoo Hyun, a bioethicist from Harvard Medical School in Boston, who was not part of the study said: 'Research groups must be clear about the scientific question they are trying to answer – and that the degree of development they allow in the model is the minimum to answer the question'.