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  4. FGF/Heparin Differentially Regulates Schwann Cell and Olfactory Ensheathing Cell Interactions with Astrocytes: A Role in Astrocytosis

FGF/Heparin Differentially Regulates Schwann Cell and Olfactory Ensheathing Cell Interactions with Astrocytes: A Role in Astrocytosis

The Journal of Neuroscience, 2007 · DOI: 10.1523/JNEUROSCI.1184-07.2007 · Published: July 4, 2007

Spinal Cord InjuryNeurologyGenetics

Simple Explanation

After spinal cord injury, astrocytes react by proliferating and forming boundaries, increasing GFAP and CSPG expression. This study investigates how Schwann cells (SCs) and olfactory ensheathing cells (OECs) interact with astrocytes. Astrocytes mingle with OECs but not SCs in vivo. SC-conditioned media induces astrocyte proliferation and CSPG expression. In OEC/astrocyte cultures, SCM induces reactive astrocytosis and boundary formation, sensitive to FGFR1 inhibition but not FGF2 alone. Heparin induces boundary formation in OEC/astrocyte cultures, while heparinase reduces it in SC/astrocyte cultures. FGF2 and FGFR1 immunoreactivity increases over grafted OECs and SCs, with HSPG over reactive astrocytes bordering the SC graft.

Study Duration
Not specified
Participants
Adult Fischer rats and purified glial cells
Evidence Level
Not specified

Key Findings

  • 1
    Schwann cell-conditioned media induces reactive astrocytosis and boundary formation in OEC/astrocyte cocultures, sensitive to FGFR1 inhibition.
  • 2
    Heparin modulates astrocyte stress response; it induces boundary formation in OEC/astrocyte cultures, while heparinase reduces it in SC/astrocyte cultures.
  • 3
    In vivo, FGF2 and FGFR1 immunoreactivity is increased over grafted OECs and Schwann cells, with HSPG increased over reactive astrocytes bordering Schwann cell grafts.

Research Summary

This study demonstrates that Schwann cells (SCs) and olfactory ensheathing cells (OECs) differentially interact with astrocytes, influencing astrocytosis following CNS injury. SC-conditioned media (SCM) induces reactive astrocytosis in OEC/astrocyte co-cultures, and this effect is sensitive to FGFR1 inhibition, suggesting a role for FGF signaling. Heparan sulfate proteoglycans (HSPGs) modulate astrocyte stress response; heparin induces boundary formation in OEC/astrocyte cultures, while heparinase reduces it in SC/astrocyte cultures.

Practical Implications

Transplantation Strategies

Understanding Schwann cell-induced astrocyte reactivity could reduce inhibitory responses and improve repair after glial cell transplantation.

Targeted Therapies

Modulating FGF/HSPG signaling could enhance the growth-promoting properties of the astrocyte-rich environment after injury.

OEC vs. SC Selection

The distinct HSPG profiles of OECs and Schwann cells suggest that OECs may induce a less severe astrocyte stress response, making them potentially advantageous for transplant-mediated repair.

Study Limitations

  • 1
    The specific FGF family member responsible for boundary formation was not definitively identified.
  • 2
    The precise mechanism by which HSPGs modulate FGF2 activity requires further investigation.
  • 3
    The study primarily used in vitro assays, and further in vivo studies are needed to fully validate the findings.

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