Aging restricts the ability of mesenchymal stem cells to promote the generation of oligodendrocytes during remyelination

Glia, 2019 · DOI: 10.1002/glia.23624 · Published: July 1, 2019

Simple Explanation

Multiple sclerosis (MS) damages the brain and spinal cord, leading to neurological problems. Mesenchymal stem cells (MSCs) are being explored as a potential cell therapy for MS because they can reduce inflammation, protect nerve cells, and promote the formation of oligodendrocytes, which are essential for myelin production. This study investigates how aging affects the ability of MSCs to support oligodendrocyte production and myelin regeneration. The researchers found that MSCs from aged rats had a reduced capacity to stimulate oligodendrocyte differentiation. They also observed that aged MSCs were less effective at enhancing myelin-like sheath formation in cerebellar slice cultures. In a rat model of MS, aged MSCs were unable to boost oligodendrocyte progenitor cell differentiation during remyelination. These findings suggest that the age of MSCs can impact their effectiveness in promoting myelin regeneration. This has implications for the design of MSC-based therapies for older MS patients, potentially requiring the use of younger donor MSCs to improve treatment outcomes.

Study Duration

Not specified

Participants

Fischer 344 rats, Sprague–Dawley rats

Evidence Level

Not specified

Key Findings

1
MSCs derived from aged rats have a reduced capacity to induce oligodendrocyte differentiation of adult CNS stem/progenitor cells.
2
Aging also abolished the ability of MSCs to enhance the generation of myelin-like sheaths in demyelinated cerebellar slice cultures.
3
In a rat model for CNS demyelination, aging suppressed the capability of systemically transplanted MSCs to boost oligodendrocyte progenitor cell (OPC) differentiation during remyelination.

Research Summary

This study investigates the impact of aging on the ability of mesenchymal stem cells (MSCs) to promote oligodendrocyte generation and remyelination, processes crucial for treating demyelinating diseases like multiple sclerosis (MS). The findings indicate that MSCs from aged rats have a diminished capacity to induce oligodendrocyte differentiation and enhance myelin-like sheath formation, both in vitro and in vivo. The research suggests that the age of MSCs is a critical factor in their therapeutic potential for MS, with implications for the design of autologous MSC-based therapies for older patients, potentially requiring the use of younger donor cells.

Practical Implications

Therapeutic Design

The findings may impact on the design of therapies using autologous MSCs in older MS patients.

Donor Selection

The use of young-donor derived MSCs, for example, umbilical cord-derived MSCs, might be more efficient than autologous MSCs from elderly patients.

Pharmacological intervention

A continuous pharmacological supply of the MSC-derived oligodendrogenic factor(s), which still need to be identified, could have a controlled and specific effect in the generation of new oligodendrocytes enhancing remyelination.

Study Limitations

1
The specific oligodendrocyte differentiation factor(s) released by MSCs remain unidentified.
2
The study primarily used rat models, and further research is needed to confirm these findings in human subjects.
3
The long-term effects of MSC transplantation and its impact on overall disease progression were not assessed.

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