Pericytes Favor Oligodendrocyte Fate Choice in Adult Neural Stem Cells

Frontiers in Cellular Neuroscience, 2019 · DOI: 10.3389/fncel.2019.00085 · Published: March 27, 2019

Simple Explanation

Multiple sclerosis (MS) damages the protective myelin sheath around nerve fibers in the central nervous system. The body can sometimes repair this damage through a process called remyelination, using cells called oligodendrocyte progenitor cells (OPCs). However, this repair often fails in advanced MS. This study investigates whether pericytes (PCs), cells surrounding blood vessels in the brain, can influence neural stem cells (NSCs) to become myelin-producing cells. They found that NSCs exposed to factors secreted by PCs were more likely to become oligodendrocytes, the cells that produce myelin. The researchers identified that a specific protein, Laminin alpha2 (Lama2), secreted by PCs, plays a crucial role in directing NSCs towards becoming oligodendrocytes rather than other types of brain cells like astrocytes. This suggests PCs and Lama2 could be potential targets for new MS therapies.

Study Duration

1 week

Participants

Female Fisher 344 rats, 6–8 weeks old

Evidence Level

In vitro study

Key Findings

1
Conditioned medium from pericytes (PC-CM) significantly increased the expression of oligodendroglial markers in adult neural stem cells (NSCs).
2
PC-CM increased Olig2 mRNA expression and reduced Id2 mRNA expression, indicating a shift towards oligodendrocyte fate and away from astrocyte fate.
3
Blocking Lama2 in PC-CM prevented the generation of oligodendrocytes, suggesting that Lama2 secreted by PCs induces NSC differentiation towards oligodendrocytes.

Research Summary

This study investigates the role of pericytes (PCs) in influencing the fate of adult neural stem cells (NSCs) towards oligodendrocyte differentiation, which is crucial for remyelination in multiple sclerosis (MS). The researchers found that soluble factors released by PCs, particularly Laminin alpha2 (Lama2), induce NSCs to differentiate into oligodendrocytes at the expense of astrocytes, suggesting a regenerative role of PCs in CNS repair. These findings suggest that targeting PCs and Lama2 could be a potential therapeutic strategy for promoting remyelination and treating MS.

Practical Implications

Therapeutic Target for MS

Pericytes and Lama2 could be targeted to develop new therapies promoting remyelination in MS.

Understanding CNS Repair

The study provides insights into the mechanisms underlying CNS repair and the role of perivascular cells in this process.

Cell-Based Therapies

Pericyte-based therapies could be explored to enhance oligodendrocyte production in demyelinating diseases.

Study Limitations

1
The study was conducted in vitro, and the findings need to be validated in vivo.
2
The specific mechanisms by which Lama2 induces oligodendrocyte fate choice require further investigation.
3
The study focused on NSCs from the hippocampus; the response of NSCs from other brain regions may differ.

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