Glial restricted precursors maintain their permissive properties after long-term expansion but not following exposure to pro-inflammatory factors

Brain Res, 2015 · DOI: 10.1016/j.brainres.2015.10.022 · Published: December 10, 2015

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Glial restricted precursors (GRPs) are a type of cell that shows promise for treating spinal cord injuries because they can create an environment that supports nerve fiber growth. This study investigated whether GRPs maintain their beneficial properties after being grown in large numbers in the lab, a process necessary for transplantation therapies. The researchers found that GRPs grown for extended periods still had the ability to promote nerve fiber growth, similar to GRPs grown for shorter periods. However, when GRPs were exposed to inflammatory substances, their growth-promoting effects were reduced. This suggests that while GRPs can be expanded for transplantation without losing their key properties, it's important to control inflammation in the injured spinal cord to ensure the GRPs can effectively support nerve regeneration.

Study Duration

Not specified

Participants

Adult Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
Late passage GRP (grown over 120 days) maintained growth-promoting effects on neurite outgrowth from adult rat DRG, comparable to early passage GRP, in both co-culture and conditioned medium experiments.
2
Exposure to pro-inflammatory mediators (LPS and IFNɤ) altered the phenotype of GRP and attenuated their growth-promoting effects on neurite outgrowth in a dose-dependent manner.
3
Late passage GRP exhibited reduced proliferation rate and some phenotypic changes (increase of GFAP+ and decrease of A2B5+), but overall maintained their immature/stem cell properties.

Research Summary

This study examined the properties of glial progenitors after long term culturing and following exposure to inflammatory mediators to assess their potential for SCI repair. The results demonstrated that late passage GRP maintained their permissive properties on neurite outgrowth in both direct DRG-GRP co-culture and conditioned medium assays, suggesting that secreted factors from GRP are sufficient to promote neurite outgrowth. However, GRP treatment with the pro-inflammatory combination of LPS-IFNɤ reduces the permissive properties of GRP with respect to promoting neurite outgrowth in a dose dependent manner.

Practical Implications

Therapeutic Potential

GRP can be expanded in vitro for transplantation therapy in SCI repair due to their maintained permissive characteristics.

Inflammatory Modulation

Modulating the inflammatory environment of the injured CNS is crucial to enhance the efficacy of GRP transplants.

In Vitro Screening

The in vitro co-culture system is valuable for testing and screening cell properties before applying them to transplantation protocols.

Study Limitations

1
Possible effect of cells from dissociated DRG (e.g. Schwann cells) has not been completely excluded
2
The study focuses on in vitro results, requiring further in vivo validation.
3
Other molecules associated with compromised blood-brain barrier can also affect astrocytes and change their morphological and functional properties as part of the pro-inflammatory cascade.

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