Concise Review: Laying the Groundwork for a First-In-Human Study of an Induced Pluripotent Stem Cell-Based Intervention for Spinal Cord Injury

STEM CELLS, 2019 · DOI: 10.1002/stem.2926 · Published: January 1, 2019

Spinal Cord Injury Regenerative Medicine

Simple Explanation

This article reviews the preparation for the first human trial of iPSC-based cell therapy for spinal cord injury, including addressing safety and tumorigenesis issues. Practical problems that must be overcome to enable therapeutic interventions for patients with chronic spinal cord injury are described. The review outlines the preparations for first-in-human trials of iPSCs-based cell transplant interventions for subacute SCI under the new Japanese legal system for regenerative medicine.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
Pre-evaluation of iPSCs and iPSC-NSPCs before transplantation is essential for the detection of “dangerous” iPSC-NS/PCs.
2
Pretreatment of iPSC-NS/PCs with GSI before transplantation promoted neuronal differentiation and prevented tumor formation, even for “dangerous” clone-derived NS/PCs.
3
The trinity of stem cell transplantation, medication, and rehabilitation thus appears to be the way forward for overcoming chronic SCI.

Research Summary

This review discusses the preparation for a first-in-human clinical study of iPSC-based cell transplant for subacute SCI, conducted under Japan’s Act on the Safety of Regenerative Medicine. The study uses neural stem/progenitor cells derived from a clinical-grade, integration-free human iPSC stock generated by the Kyoto University Center for iPS Cell Research and Application. The review addresses safety and tumorigenesis concerns, as well as practical issues that must be overcome for therapeutic interventions in chronic SCI patients.

Practical Implications

Enhanced Safety Protocols

The planned clinical trial program must meet higher safety standards due to the gene transfer process in generating iPSCs and the long culture period for differentiation.

Allogeneic iPSC Use

The first-in-human clinical study opted to use clinical-grade allogenic iPSC clones produced by CiRA, which have already passed through quality and safety tests, due to time and expense issues with autologous iPSCs.

Combination Therapies

Future treatments should aim for the most effective reconstruction of organized neural circuits by iPSC-based cell therapy after chemical suppression of axon growth inhibitory factors and rehabilitation.

Study Limitations

1
The generation of autologous human iPSC-NS/PCs takes at least 6 months, and several additional months are needed for safety testing, posing time and expense obstacles.
2
It is extremely difficult to obtain longer survival (over 1 year) for immune-deficient mice in preclinical safety testing.
3
Although several important findings on stem cell transplantation and medication approaches for chronic SCI have been reported in recent years, none promises to fully restore function.

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