Macrophages Treated with VEGF and PDGF Exert Paracrine Effects on Olfactory Ensheathing Cell Function

Cells, 2022 · DOI: 10.3390/cells11152408 · Published: August 4, 2022

Simple Explanation

This study investigates how olfactory ensheathing cells (OECs) can be used to treat spinal cord injuries (SCI). OECs help promote neuron growth, but it's hard for them to survive at the injury site. Macrophages, which are immune cells, also show up at the injury site and can affect OECs. The researchers looked at whether two growth factors, VEGF and PDGF, could change how macrophages interact with OECs and improve their function. The study found that VEGF and PDGF can affect macrophages in a way that helps OECs to clear debris and express genes related to nerve repair. This suggests that using these growth factors together with OEC transplantation could be a good strategy for SCI therapy.

Study Duration

Not specified

Participants

C57Bl/6 mice, S100β-DsRed transgenic mouse pups, S100β-DsRed transgenic mice

Evidence Level

In vitro study

Key Findings

1
Combined VEGF + PDGF reduced translocation nuclear factor kappa B p65 in macrophages without altering pro-inﬂammatory cytokines.
2
Conditioned medium from macrophages incubated with PDGF and combined VEGF + PDGF in inﬂammatory conditions promoted phagocytosis by OECs.
3
The growth factor treated conditioned media also modulated the expression of genes associated with nerve repair and myelin expression in OECs.

Research Summary

This study assessed how macrophage conditioned medium affects the phagocytic ability and gene expression pattern in OECs and the inﬂuence of the growth factors VEGF and PDGF. Macrophages exposed to combined VEGF + PDGF for 24 h had reduced nuclear factor kappa B p65 translocation. Conditioned medium from macrophages incubated with PDGF and combined VEGF + PDGF in inﬂammatory conditions promoted phagocytosis by OECs (48 h MCM; Figure 3K).

Practical Implications

Combination Therapy Potential

VEGF and PDGF, combined with OEC transplantation, may offer a promising therapeutic strategy for SCI.

Optimizing Growth Factor Treatment Duration

The timing of growth factor administration is crucial, as OEC function and gene expression change over time and are influenced by macrophage paracrine effects.

Macrophage Modulation Benefits

PDGF and combined VEGF + PDGF exhibit beneficial effects by reducing pro-inflammatory cytokines, promoting myelin debris phagocytosis, and enhancing nerve repair gene expression in OECs.

Study Limitations

1
Bone marrow derived macrophages play a major role in SCI, and may have a variable in vitro outcome in comparison to peritoneal macrophages.
2
Further assessment with protein quantiﬁcation in both cytoplasm and nuclei in macrophages would provide conﬁrmation of NF-κB study.
3
All ﬁndings are based on 70–80% of the OEC population.

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