Developmental stage of transplanted neural progenitor cells inﬂuences anatomical and functional outcomes after spinal cord injury in mice

Communications Biology, 2023 · DOI: https://doi.org/10.1038/s42003-023-04893-0 · Published: May 2, 2023

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study explores how the age of neural progenitor cells (NPCs) used in transplants after spinal cord injury (SCI) affects the outcome. They transplanted NPCs from mouse embryos of different ages (E11.5, E12.5, E13.5) into adult mice with SCI and observed the effects. The researchers looked at how well the transplanted cells grew, what types of cells they became, how they interacted with the host's spinal cord, and how the mice recovered motor and sensory functions. They found that the age of the transplanted cells significantly influenced these factors. Ultimately, this research helps to refine cell transplantation strategies for spinal cord injury by showing that the developmental stage of donor cells is critical for achieving desired outcomes, paving the way for more tailored and effective therapies.

Study Duration

4 weeks post-transplantation

Participants

n = 310 mice, n = 12 F344 rats

Evidence Level

Not specified

Key Findings

1
Earlier-stage NPC grafts (E11.5) exhibited greater axon outgrowth, enrichment for ventral spinal cord interneurons and Group-Z spinal interneurons, and enhanced host 5-HT+ axon regeneration compared to later-stage grafts.
2
Later-stage NPC grafts (E13.5) were enriched for late-born dorsal horn interneuronal subtypes and Group-N spinal interneurons, supported more extensive host CGRP+ axon ingrowth, and exacerbated thermal hypersensitivity.
3
Locomotor function was not significantly affected by any type of NPC graft.

Research Summary

The study investigates how the developmental stage of transplanted neural progenitor cells (NPCs) affects anatomical and functional outcomes after spinal cord injury (SCI) in mice. Results indicate that earlier-stage NPC grafts show greater axon outgrowth and promote serotonergic axon regeneration, while later-stage grafts enhance CGRP+ axon ingrowth and exacerbate thermal hypersensitivity. Despite differences in anatomical outcomes, no significant improvement in locomotor function was observed with any NPC graft type.

Practical Implications

Tailored Cell Therapies

The findings suggest that the developmental stage of donor NPCs should be carefully considered to optimize graft cellular composition and achieve specific therapeutic goals, such as promoting motor recovery or modulating sensory function.

Refined Experimental Design

Researchers should be aware that the developmental stage of NPCs can significantly influence graft outcomes, potentially affecting the reproducibility and interpretation of SCI/transplantation studies.

Improved Understanding of Graft Biology

The study highlights the importance of understanding the cellular diversity within NPC grafts and how this diversity influences the integration of grafts with host neural circuits, potentially leading to more effective graft designs.

Study Limitations

1
The study did not observe locomotor functional improvement with any graft types, which contrasts with previous reports.
2
Isolation of E11.5 spinal cords is more difficult and yields fewer cells compared to later embryonic stages.
3
The study lacks corticospinal tracing to assess how graft cellular composition influences regeneration of these and other functionally important axon projections.

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