The Development of a Pro-regenerative Myeloid Cell
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Date
2022-05
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The Ohio State University
Abstract
The unique inability of adult human neurons in the CNS to regenerate following acute injury has prompted significant research efforts into developing a treatment that can induce regeneration of these damaged neurons and restore functionality of the nervous pathway. Sas et al. were able to find a subpopulation of immature murine neutrophils that was capable of stimulating robust axon regrowth in retinal ganglion cells (RGC) following optic nerve crush (ONC). Murine bone marrow (BM) cells were then cultured with various polarizing factors in vitro to see if these cells could be polarized to a neuroprotective phenotype (Jerome, unpublished). It was found that culturing these BM cells with a combination of IL-4 and G-CSF promoted increased pro-regenerative properties and upregulated similar markers of alternative activation seen in murine neutrophils found by Sas et al. Therefore, in this project, I wanted to see if immature human neutrophils could also be cultured with polarizing factors in vitro to induce a more pro-regenerative phenotype. We found that treatment with IL-4 resulted in alternative activation of human umbilical cord cells, as indicated by decreased expression of maturity markers CD16 and CD66b. In addition, CD124 expression decreased, suggesting that IL-4 binding to its receptor is involved in this alternative activation. Further experimentation can be conducted to determine the pro-regenerative capabilities of these IL-4 activated cells or discover novel factors that can polarize immature human neutrophils to a phenotype capable of restoring function to a damaged nervous pathway.
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Keywords
Neutrophil, Myeloid cell, inflammation, neuroprotective, pro-regenerative, neurodegeneration, polarization