Pre-clinical evaluation of clinically relevant iPS cell derived neuroepithelial stem cells as an off-the-shelf cell therapy for spinal cord injury

Front. Pharmacol., 2024 · DOI: 10.3389/fphar.2024.1390058 · Published: May 22, 2024

Spinal Cord Injury Pharmacology Regenerative Medicine

Simple Explanation

This study explores the potential of using a specific type of stem cell, called neuroepithelial stem (NES) cells, derived from induced pluripotent stem (iPS) cells, as a ready-to-use (off-the-shelf) therapy for spinal cord injury (SCI). The researchers created these NES cells under strict manufacturing guidelines to ensure they are safe and of high quality for potential clinical use. The study found that these NES cells can be frozen and thawed without losing their ability to function, opening the door for a more accessible and consistent cell therapy for SCI.

Study Duration

2 years

Participants

Healthy male donor (skin biopsy) and rats (spinal cord injury model)

Evidence Level

Pre-clinical study

Key Findings

1
Cryopreserved NES cells maintain high cell viability and retain their cell identity and differentiation capacity after thawing.
2
The manufacturing process yields stable cell doses with minimal batch-to-batch variability and consistent expression of identity markers.
3
Cryopreserved NES cell doses exhibit sustained viability, functionality, and quality for at least 2 years.

Research Summary

This study provides proof of concept for an off-the-shelf NES cell-based therapy for SCI using cryopreserved doses derived from clinically relevant and GMP cleanroom-produced iPS cell lines. The research demonstrates a process to manufacture, cryopreserve, and characterize iPS cell-derived NES cell therapy doses with consistent good quality for preclinical trials and potential for treating humans. The study highlights the importance of using frozen off-the-shelf cell therapy products as a safer, more efficient, and sustainable approach for iPS cell-derived cell therapy in the future.

Practical Implications

Clinical Translation

The study facilitates clinical translation by using standardized iPS cell lines derived in xeno-free and chemically defined conditions, with one line manufactured under GMP in approved cleanrooms.

Quality Control

Cryopreservation facilitates extensive quality control testing before cell grafting, opening new opportunities to standardize and optimize cell doses in preparation for human clinical trials.

Cost-Effectiveness

The ability to cryopreserve cells enables the manufacturing of large, cost-effective batches, improving the accessibility and affordability of cell therapies.

Study Limitations

1
Even with a robust and standardized protocol, cell viability after thawing is slightly different depending on the person manufacturing the cell therapy doses.
2
The in vitro experiments merely serve as proof of the functional capacity of the cells to differentiate despite having been subjected to cryopreservation at different stages.
3
For future experiments and QCs a different set of marker genes might be needed to reliably show that no pluripotent cells remained in the cell therapy doses pre-transplantation.

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