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

Souptik Basu; Indra N Choudhury; Jia Yu Peppermint Lee; Anu Chacko; Jenny A K Ekberg; James A St John

doi:10.3390/cells11152408

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

Cells. 2022 Aug 4;11(15):2408. doi: 10.3390/cells11152408.

Authors

Souptik Basu^{1

2}, Indra N Choudhury^{1

2}, Jia Yu Peppermint Lee¹, Anu Chacko^{1

2}, Jenny A K Ekberg^{1

2

3}, James A St John^{1

2

3}

Affiliations

¹ Clem Jones Centre for Neurobiology and Stem Cell Research, Nathan Campus, Griffith University, Nathan, QLD 4222, Australia.
² Menzies Health Institute Queensland, Southport Campus, Griffith University, Southport, QLD 4222, Australia.
³ Griffith Institute for Drug Discovery, Nathan Campus, Griffith University, Nathan, QLD 4111, Australia.

Abstract

Glial cell transplantation using olfactory ensheathing cells (OECs) holds a promising approach for treating spinal cord injury (SCI). However, integration of OECs into the hostile acute secondary injury site requires interaction and response to macrophages. Immunomodulation of macrophages to reduce their impact on OECs may improve the functionality of OECs. Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), known for their immunomodulatory and neuroprotective functions, have provided improved outcomes in SCI animal models. Thus, VEGF and PDGF modulation of the SCI microenvironment may be beneficial for OEC transplantation. In this in vitro study, the effect of VEGF and PDGF on macrophages in an inflammatory condition was tested. Combined VEGF + PDGF reduced translocation nuclear factor kappa B p65 in macrophages without altering pro-inflammatory cytokines. Further, the ability of OECs to phagocytose myelin debris was assessed using macrophage-conditioned medium. Conditioned medium from macrophages incubated with PDGF and combined VEGF + PDGF in inflammatory conditions promoted phagocytosis by OECs. The growth factor treated conditioned media also modulated the expression of genes associated with nerve repair and myelin expression in OECs. Overall, these results suggest that the use of growth factors together with OEC transplantation may be beneficial in SCI therapy.

Keywords: NF-κB; glia; growth factor; myelin; phagocytosis; spinal cord injury.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Culture Media, Conditioned / pharmacology
Macrophages
Nerve Regeneration / physiology
Olfactory Bulb
Platelet-Derived Growth Factor / pharmacology
Spinal Cord Injuries* / therapy
Vascular Endothelial Growth Factor A*

Substances

Culture Media, Conditioned
Platelet-Derived Growth Factor
Vascular Endothelial Growth Factor A

Grants and funding

This work is supported by a Clem Jones Foundation grant to JS and JE, a Motor Accident Insurance Commission Queensland Grant to JS and JE, a National Health and Medical Research Council Grant to JS and JE (APP1183799), a Perry Cross Spinal Research Foundation Grant to JE and JS, and Griffith University International Postgraduate Research Scholarships to SB and IC.