ImmuneDrivenRepair 

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

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

     

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