A Narrative Review of Advances in Neural Precursor Cell Transplantation Therapies for Spinal Cord Injury

Neurospine, 2022 · DOI: https://doi.org/10.14245/ns.2244628.314 · Published: December 1, 2022

Spinal Cord Injury Regenerative Medicine

Simple Explanation

Spinal cord injury (SCI) leads to permanent neurological deficits due to the limited regenerative capacity of the nervous system. Transplantation therapies, particularly using neural precursor cells (NPCs), offer a promising approach to restore function by rebuilding neuronal circuits and protecting nerve cells. Researchers have developed methods to derive NPCs from human induced pluripotent stem cells (hiPSCs) and have shown functional improvements in SCI animal models using these cells. These hiPSC-NPCs are now being tested in clinical trials for subacute SCI. A significant challenge remains in treating chronic SCI, requiring comprehensive strategies that combine transplantation with other therapeutic interventions to enhance efficacy.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
NPC transplantation can promote functional recovery after SCI through multiple mechanisms, including reconstruction of neuronal circuits, remyelination of axons, and neuroprotection via trophic factors.
2
The subacute phase (7-28 days post-injury) is considered the optimal time for NPC transplantation in both rodents and non-human primates due to a more favorable microenvironment.
3
hiPSC-NPCs have emerged as a leading candidate cell type for SCI transplantation due to their ability to survive in the injured spinal cord, differentiate into neural cells, integrate into host neuronal circuits, and secrete beneficial trophic factors.

Research Summary

This review discusses the advances in neural precursor cell (NPC) transplantation therapies for spinal cord injury (SCI). Transplantation of NPCs has been shown to promote functional recovery through mechanisms such as neuronal circuit reconstruction, axon remyelination, and neuroprotection. The review highlights the importance of the subacute phase as the optimal timing for transplantation and the therapeutic potential of human induced pluripotent stem cell-derived NPCs (hiPSC-NPCs). The review also addresses the safety considerations of hiPSC-NPC transplantation, including strategies to predict and prevent tumorigenicity. It concludes with a discussion of the clinical application of hiPSC-NPC transplantation and future directions for treating chronic SCI.

Practical Implications

Clinical Translation

hiPSC-NPC transplantation therapy has advanced to clinical trials for subacute SCI, offering a potential regenerative treatment option.

Combination Therapies

Treating chronic SCI requires combined approaches, such as rehabilitation, chondroitinase ABC, and Notch signaling inhibition, to overcome the challenges of the chronic injury environment.

Safety Measures

Strategies such as careful cell line selection, pretreatment with GSI, and the use of suicide genes are critical for ensuring the safety of hiPSC-NPC transplantation by preventing tumorigenicity.

Study Limitations

1
The detailed therapeutic mechanisms of NPC transplantation remain unclear.
2
The optimal strategy for complete improvement from SCI, especially in severe injury models, has yet to be determined.
3
The long-term effects of transplantation have not been proven in animal models due to their short lifespan compared to humans.

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