Two-photon imaging of remyelination of spinal cord axons by engrafted neural precursor cells in a viral model of multiple sclerosis

PNAS, 2014 · DOI: 10.1073/pnas.1406658111 · Published: May 19, 2014

Simple Explanation

This study uses stem cells to treat the nerve damage caused by multiple sclerosis (MS) in mice. Current treatments for MS only slow down the disease, but stem cell transplants can actually help reverse the damage in animals. Researchers used a special microscope to watch stem cells repair damaged nerve fibers in the spinal cord. They discovered that the transplanted stem cells physically wrap around the injured nerve fibers with a new layer of myelin, which helps protect the nerves. The study also found that the stem cells know where the damage is and move to those areas to start the repair process. This technique can visualize cellular migration and remyelination in the mouse spinal cord.

Study Duration

Not specified

Participants

Mice infected with JHMV

Evidence Level

Not specified

Key Findings

1
NPCs transplanted into spinal cords of JHMV-infected mice exhibited diminished migration velocities and increased proliferation compared with transplanted cells in noninfected mice.
2
NPCs preferentially accumulated within areas of axonal damage, initiated direct contact with axons, and subsequently expressed the myelin proteolipid protein gene, initiating remyelination.
3
Transplanted NPCs differentiated into myelinating cells and expressed myelin genes. In these cells, GFP fills the cytoplasm of the cell body, revealing that differentiated NPCs wrapped around damaged axons.

Research Summary

This study provides the first real-time imaging of transplanted stem cell-mediated remyelination in a mouse model of MS. Using two-photon microscopy and viral-induced demyelination, we describe a technique to visualize cellular migration and remyelination in the mouse spinal cord. Transplanted neural precursor cells physically wrap damaged axons with newly formed myelin, preserving axonal health.

Practical Implications

Therapeutic Potential

NPC transplantation holds promise for reversing clinical disease in MS, unlike current treatments that only delay progression.

Understanding Remyelination

The study provides insights into the mechanisms by which transplanted NPCs contribute to the amelioration of clinical and histopathological disease.

Model System

The study establishes a model system to better understand the physical nature of NPC interactions with damaged axons.

Study Limitations

1
Etiology of MS is unknown, so viral models may not fully replicate the human condition.
2
The molecular signals mediating the interaction between NPCs and damaged axons are undefined.
3
Study focuses on a mouse model; translation to human treatments requires further research.

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