Cytokine polarized, alternatively activated bone marrow neutrophils drive axon regeneration

Not specified, 2023 · DOI: https://doi.org/10.21203/rs.3.rs-3491540/v1 · Published: October 31, 2023

Regenerative Medicine Immunology Neurology

Simple Explanation

The adult central nervous system (CNS) has limited self-repair capabilities, and severed axons typically fail to regrow, creating a need for treatments to enhance neuronal viability and facilitate axon regeneration. The study demonstrates that bone marrow neutrophils, when polarized with specific cytokines, upregulate alternative activation markers and produce growth factors, gaining the capacity to promote neurite outgrowth. Transferring these polarized neutrophils into experimental models of CNS injury triggered substantial axon regeneration within the optic nerve and spinal cord, suggesting potential autologous myeloid cell-based therapies for reversing CNS damage.

Study Duration

Not specified

Participants

Mouse and human bone marrow cells

Evidence Level

Not specified

Key Findings

1
IL-4/G-CSF polarization reprograms bone marrow neutrophils (BMNs), causing them to upregulate alternative activation markers and produce cytoprotective and growth factors, akin to zymosan-modulated counterparts.
2
Adoptive transfer of IL-4/G-CSF polarized BMNΦ into experimental models of CNS injury resulted in significant axon regrowth within both the optic nerve and the spinal cord.
3
IL-4/G-CSF polarized human bone marrow cells contain a subset of immature neutrophils capable of stimulating primary human cortical neurons to grow neurites.

Research Summary

The study identifies novel populations of bone marrow-derived myeloid cells with neuroprotective and pro-regenerative properties, generated through short-term culture with IL-4 and G-CSF. These IL-4/G-CSF polarized cells, whether from mouse or human, exhibit characteristics of immature, alternatively activated neutrophils and express EGFR ligands and other neuroprotective agents. The findings offer potential for autologous myeloid-based therapies aimed at restoring lost neurological functions in conditions ranging from traumatic injury to neurodegenerative diseases.

Practical Implications

Autologous Cell Therapies

The study suggests potential development of autologous myeloid cell-based therapies for CNS repair.

Personalized Medicine

Personalized treatment strategies could be developed by harnessing autologous myeloid cells derived from the patient’s own bone marrow.

Multimodal Therapeutic Regimens

IL-4/G-CSF polarized BM myeloid cells show promise as a potent component within multimodal therapeutic regimens aimed at promoting neuroprotection and repair.

Study Limitations

1
The precise mechanisms of action of IL-4/ G-CSF polarized BMNΦ require further investigation to determine the distinctions and similarities between these populations and their potential roles across different neuropathological conditions.
2
Potential for off-target side effects require further exploration.
3
The current study requires further clinical translation.

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