Human induced pluripotent stem cell/embryonic stem cell-derived pyramidal neuronal precursors show safety and efficacy in a rat spinal cord injury model

Cellular and Molecular Life Sciences, 2024 · DOI: https://doi.org/10.1007/s00018-024-05350-9 · Published: July 5, 2024

Spinal Cord Injury Regenerative Medicine

Simple Explanation

This study explores a cell transplantation strategy for spinal cord injury (SCI) using human induced pluripotent stem cells (iPSCs) differentiated into pyramidal neuronal precursors (PNPs). These PNPs were transplanted into a rat SCI model. The transplanted rats showed improved motor functions compared to controls. The PNPs matured into corticospinal pyramidal neurons and extended axons into the host spinal cord. The PNP graft also exhibited an anti-inflammatory effect at the injury site and showed no tumor formation, suggesting safety and potential for SCI treatment.

Study Duration

8 weeks

Participants

36 female Sprague Dawley adult rats, 20 nude rats, immunodeficient mice

Evidence Level

Not specified

Key Findings

1
Transplantation of iPSC-derived PNPs into SCI rats significantly improved their motor functions compared to the control group.
2
PNPs matured into corticospinal pyramidal neurons and extended axons into distant host spinal cord tissues, primarily in a caudal direction, with host neurons also growing axons into the graft.
3
PNP graft showed an anti-inflammatory effect at the injury site, biasing microglia/macrophages towards an M2 phenotype, and demonstrated safety with no tumor formation.

Research Summary

This study investigates the use of iPSC/ESC-derived pyramidal precursor cells (PNPs) for treating spinal cord injury (SCI) in a rodent model. PNPs had a significant effect on behavioral recovery following severe SCI, significantly restoring the animals' motor function. The transplanted PNPs facilitated tissue repair and formed synaptic connections with host neurons. These synaptic connections, along with the long-distance axon projection ability of PNPs, helped reconstruct a neuronal relay circuit across the lesion site. Additionally, PNPs exerted anti-inflammatory effects at the injury site and promoted the transformation of microglia into an M2 phenotype. These findings suggest a path towards future clinical translation for SCI treatment.

Practical Implications

Therapeutic Potential

PNPs can be a promising cellular candidate for SCI treatment due to their ability to reconstruct neuronal relay circuitry across the lesion site.

Microenvironment Modulation

PNP grafts can modulate the microenvironment in SCI, potentially reducing secondary damage and promoting graft survival.

Clinical Translation

The results may pave the way for future clinical translation in treating SCI patients, especially given the observed safety profile.

Study Limitations

1
Treatment time window (same day of SCI) may not be easily realized in clinical practice.
2
Obvious differences in the functional neuroanatomy between rodents and primates.
3
Using iPSC-derivatives as a graft may need to go through more strict safety measures

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