Pre-Evaluated Safe Human iPSC-Derived Neural Stem Cells Promote Functional Recovery after Spinal Cord Injury in Common Marmoset without Tumorigenicity

PLoS ONE, 2012 · DOI: 10.1371/journal.pone.0052787 · Published: December 27, 2012

Spinal Cord Injury Regenerative Medicine

Simple Explanation

This study investigates the potential of using human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) to treat spinal cord injury (SCI) in a non-human primate model. The researchers transplanted pre-evaluated "safe" hiPSC-NS/PCs into marmosets with SCI and observed their effects on functional recovery and tumor formation. The results showed that the transplanted cells survived, differentiated into neural lineages, enhanced axonal regrowth, promoted angiogenesis, and prevented demyelination, leading to functional recovery without tumor formation.

Study Duration

12 weeks

Participants

Adult female common marmosets

Evidence Level

Not specified

Key Findings

1
Grafted hiPSC-NS/PCs survived and differentiated into neurons, astrocytes, and oligodendrocytes without tumor formation in the injured spinal cord of common marmosets.
2
Transplantation of hiPSC-NS/PCs prevented demyelination after SCI, as evidenced by LFB and EC staining, as well as conventional MRI and Myelin map imaging.
3
Grafted hiPSC-NS/PCs enhanced axonal sparing/regrowth and angiogenesis, as demonstrated by immunostaining for NF-200, CaMK-IIa, and PECAM-1.

Research Summary

This study demonstrates that pre-evaluated safe hiPSC-NS/PCs can promote functional recovery after SCI in a common marmoset model without causing tumor formation. The transplanted cells survived and differentiated into neural lineages, enhanced axonal sparing/regrowth, promoted angiogenesis, and prevented demyelination. These findings suggest that hiPSC-NS/PCs are a promising source of cells for clinical intervention following SCI, although further safety assessments are needed.

Practical Implications

Potential Therapeutic Application

Pre-evaluated safe hiPSC-NS/PCs could be a potential cell source for treating SCI in humans.

Improved Functional Recovery

Transplantation of hiPSC-NS/PCs can enhance axonal sparing/regrowth and angiogenesis, leading to better functional outcomes after SCI.

Reduced Demyelination

hiPSC-NS/PCs can prevent demyelination at the lesion epicenter, potentially preserving neural function.

Study Limitations

1
The study observed animals for tumor formation for only up to 12 weeks after cell transplantation, thus long term effects are unknown.
2
The hiPSC-NS/PCs did not differentiate into mature myelin basic protein (MBP)-positive oligodendrocytes during the course of the experiment, perhaps because the period of observation was too short.
3
Further study using integration-free hiPSC [62,63,64,65,66,67,68,69,70,71]-derived NS/PCs is required to validate the safety of such cells for stem cell interventions following SCI.

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