Generation of spinal motor neurons from human fetal brain-derived neural stem cells: role of basic fibroblast growth factor

J Neurosci Res, 2009 · DOI: 10.1002/jnr.21856 · Published: February 1, 2009

Regenerative Medicine Neurology Genetics

Simple Explanation

Neural stem cells (NSCs) can change their fate when exposed to specific signals. This study investigates how a protein called basic fibroblast growth factor (bFGF) influences human NSCs to become a specific type of nerve cell. The research shows that bFGF can cause NSCs from the human fetal brain to develop into cholinergic neurons, which have properties similar to spinal motor neurons. This process involves bFGF causing the NSCs to express a marker called Hb9, which is specific to motor neurons. Blocking bFGF prevents this from happening.

Study Duration

Not specified

Participants

Human fetal (8–10 weeks) cortical NSCs, lines K048 and K054

Evidence Level

Not specified

Key Findings

1
bFGF induces human NSCs to express the motor neuron marker Hb9.
2
Development of spinal motor neuron properties is independent of selective proliferation or survival.
3
bFGF-induced Hb9 expression is both dose- and time-dependent.

Research Summary

This study demonstrates that human fetal cortical NSCs can be induced to express spinal motor neuron characteristics in vitro by bFGF. bFGF enhances the expression of ventral markers such as Olig2 in human cortical NSCs, indicating a ventralizing effect. bFGF acts as an instructive factor for neuronal subtype determination of hNSCs, independent of cell proliferation and survival.

Practical Implications

Clinical Applications

The findings have implications for exploring the potential of brain NSCs for clinical applications, particularly spinal motor neuron regeneration.

Understanding NSC Plasticity

The study provides new evidence to support the hypothesis that NSCs are uncommitted and highly plastic, as shown by their losing original region-specific transcription factor identities.

Drug development

The study highlights the importance of bFGF in directing stem cell fate and specific neuronal subtypes which can be used to develop new drugs.

Study Limitations

1
The in vitro cultured hNSCs may not completely mimic the behavior of those cells during development in vivo.
2
The study focused on MAPK pathways, and other pathways in the FGF signaling network need to be more intensively examined.
3
The exact mechanisms underlying differential effects of bFGF vs. EGF on MEK/ERK signaling in hNSCs require further investigation.

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