The Segal lab has discovered a unique myeloid cell subset, with characteristics of immature neutrophils, that are capable of stimulating the regrowth of damaged axons. These cells express the cell surface phenotype Ly6Glow CD14+. Adoptive transfer of the Ly6Glow CD14+ cells directly into the posterior chamber of the eyes of mice with optic nerve crush injury induces the regeneration of transected axons in vivo. Furthermore, co-culture of Ly6Glow CD14+ cells, or their conditioned media, with dissociated neurons stimulates neurite outgrowth in vitro. We have identified a panoply of growth factors secreted by the pro-regenerative neutrophils that are critical to their mechanism of action.
Ongoing Projects:
- Interrogation of the growth factors, cytokines, chemokines and adhesion molecules that drive the differentiation of pro-regenerative neutrophils in vivo and orchestrate their migration to sites of CNS injury
- Further characterization of the mechanism of action of pro-regenerative neutrophils and translation of the knowledge gained towards the development of novel reparative therapies for chronic CNS diseases
- Generation of pro-regenerative neutrophils from bone marrow precursors in vitro (via culture with cytokine cocktails) for re-infusion to individuals with CNS injury as an autologous cellular therapy
- Assessment of the therapeutic potential of pro-regenerative neutrophils in spinal cord and brain trauma models
- Investigation of human pro-regenerative neutrophils
Related Publication:
- Baldwin KT, Carbajal KS, Giger RJ, Segal BM. Neuroinflammation triggered by a β-glucan/ dectin-1 signaling enables CNS regeneration. Proc Nat Acad Sci 2015;112(8): 2581-6. PMID: 25675510
- Sas AR, Carbajal KS, Jerome AD, Menon R, Yoon C, Kalinski AL, Giger RJ, Segal BM.
A new neutrophil subset promotes CNS neuron survival and axon regeneration. Nat Immunol. 2020 Dec;21(12):1496-1505 PMID: 33106668 - Jerome AD, Sas AR, Wang Y, Wen J, Atkinson JR, Webb A, Liu T, Segal BM. Cytokine polarized, alternatively activated bone marrow neutrophils drive axon regeneration. Nat Immunol. 2024 Jun;25(6):957-968. PMID: 37961609
Related Funding:
- National Institutes of Health (R01EY029159)
A novel inflammatory cell with neuroprotective and neuroregenerative properties - National Institutes of Health (R01EY028350)
Immune mediated regeneration of retinal ganglion cell axons following optic nerve trauma