Human spinal GABA neurons survive and mature in the injured nonhuman primate spinal cord

Stem Cell Reports, 2023 · DOI: https://doi.org/10.1016/j.stemcr.2022.12.016 · Published: January 19, 2023

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Spinal cord injury (SCI) often results in permanent loss of neural function due to the inability of damaged neurons to regenerate and restore destroyed neural circuits. This study explores the potential of using human stem cell-derived spinal GABA neurons to repair the injured spinal cord in a nonhuman primate model. The researchers transplanted human spinal GABA neurons into the injured spinal cords of rhesus macaques. They found that these transplanted neurons survived for up to 7.5 months, matured, and grew axons, forming synapses within the monkey's spinal cord. This suggests that human spinal neurons can integrate into the host's neural circuitry. The study also demonstrated that the transplanted human neurons were functionally active, as evidenced by their response to DREADD activation. This indicates that the neurons could potentially modulate neural activity in the injured spinal cord, representing a significant step toward clinical translation for treating SCI.

Study Duration

7.5 months

Participants

4 adult male rhesus macaques

Evidence Level

Not specified

Key Findings

1
Human spinal GABA neurons, derived from pluripotent stem cells, can survive for up to 7.5 months after transplantation into the injured spinal cord of rhesus macaques.
2
The transplanted human neurons mature, extend axons, and form synapses within the host monkey's spinal cord, indicating integration with the existing neural circuitry.
3
Designer receptors exclusively activated by designer drug (DREADD) activation confirmed that the transplanted neurons were functionally alive.

Research Summary

This study investigates the feasibility of using human pluripotent stem cell (hPSC)-derived spinal GABA neurons to treat spinal cord injury (SCI) in a nonhuman primate (NHP) model. The researchers established an NHP model of SCI in rhesus macaques by hemisecting the T10 spinal cord, resulting in neural dysfunction. Human spinal GABA neurons were then grafted into the injured spinal cord. The grafted human spinal GABA neurons survived for up to 7.5 months, matured, grew axons, and formed synapses in the injured monkey spinal cord. DREADD activation confirmed their functionality, suggesting a significant step toward clinical translation for SCI treatment.

Practical Implications

Clinical Translation Potential

The study's findings support the potential for using human spinal neuron transplantation as a therapeutic strategy for treating spinal cord injury in humans.

Further Research

The successful integration and functionality of the transplanted neurons warrant further investigation into their long-term effects on functional recovery and potential side effects.

Refining Transplantation Techniques

Further optimization of transplantation techniques, such as increasing the number of grafted cells and using biomaterials to support cell survival and maturation, could enhance the therapeutic benefits.

Study Limitations

1
The study only involved a small sample size (four monkeys), which limits the generalizability of the findings.
2
The hSyn antibody can recognize monkey synapses, making it uncertain whether these synapses authentically originate from human neurons
3
The study only assessed the survival and maturation of the transplanted neurons, without a comprehensive evaluation of functional recovery.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury