Accelerated differentiation of human induced pluripotent stem cells into regionally speciﬁc dorsal and ventral spinal neural progenitor cells for application in spinal cord therapeutics

Front. Neurosci., 2023 · DOI: 10.3389/fnins.2023.1251906 · Published: September 15, 2023

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This research focuses on creating spinal cord cells from human induced pluripotent stem cells (hiPSCs) for spinal cord injury (SCI) treatment. The study details a method to quickly produce both dorsal (sensory) and ventral (motor) spinal cord progenitor cells. The process allows creation of these cells from the same starting population, reducing variability and improving the potential for spinal cord repair through cell transplantation.

Study Duration

Not specified

Participants

Four established hiPSC cell lines from healthy donors

Evidence Level

Original Research

Key Findings

1
The study successfully developed a rapid differentiation protocol, generating neural progenitors in 6 days and post-mitotic neurons in 20 days.
2
The protocol allows for the creation of both dorsal and ventral spinal domains from a shared hiPSC lineage.
3
The generated dorsal spinal neurons exhibit expression of markers associated with all mature interneuron subtypes.

Research Summary

This study addresses the need for region-specific cell types in spinal cord injury research by developing standardized protocols to create hiPSC-derived spinal cord progenitors. The rapid induction approach allows production of neural progenitors in 6 days and post-mitotic neurons in twenty, while most protocols require a minimum of 30 days. The inclusion of the dorsal spinal domain represents a neglected area of research, with the ventral and motor domain being overrepresented in the literature.

Practical Implications

Improved Cell Transplantation

The developed technology can be used with biomaterials and pharmacology to enhance cell transplantation for spinal cord injury, increasing neuroregeneration potential.

Advancement of SCI Research

The rapid differentiation protocol and generation of both dorsal and ventral spinal neurons from a shared lineage can improve understanding and outcomes after spinal cord injury.

Therapeutic Development

The study provides a critical step toward consistent differentiation protocols for hiPSC-derived spinal neurons, with potential applications for in vitro modeling and in vivo transplantation.

Study Limitations

1
Variability in subtype-specific marker expression at both progenitor and post-mitotic states.
2
Potential for off-target neural crest formation due to BMP usage.
3
Lack of comprehensive human atlases for spinal cord development complicates marker selection.

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