Systemic neutrophil depletion modulates the migration and fate of transplanted human neural stem cells to rescue functional repair

Hal X. Nguyen, Mitra J. Hooshmand, Hirokazu Saiwai, Jake Maddox, Arjang Salehi, Anita Lakatos, Rebecca A. Nishi, Desiree Salazar, Nobuko Uchida, Aileen J. Anderson

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

The interaction of transplanted stem cells with local cellular and molecular cues in the host CNS microenvironment may affect the potential for repair by therapeutic cell populations. In this regard, spinal cord injury (SCI), Alzheimer’s disease, and other neurological injuries and diseases all exhibit dramatic and dynamic changes to the host microenvironment over time. Previously, we reported that delayed transplantation of human CNS-derived neural stem cells (hCNS-SCns) at 9 or 30 d post-SCI (dpi) resulted in extensive donor cell migration, predominantly neuronal and oligodendrocytic donor cell differentiation, and functional locomotor improvements. Here, we report that acute transplantation of hCNS-SCns at 0 dpi resulted in localized astroglial differentiation of donor cells near the lesion epicenter and failure to produce functional improvement in an all-female immunodeficient mouse model. Critically, specific immunodepletion of neutrophils (polymorphonuclear leukocytes) blocked hCNS-SCns astroglial differentiation near the lesion epicenter and rescued the capacity of these cells to restore function. These data represent novel evidence that a host immune cell population can block the potential for functional repair derived from a therapeutic donor cell population, and support targeting the inflammatory microenvironment in combination with cell transplantation after SCI.

Original languageEnglish
Pages (from-to)9269-9287
Number of pages19
JournalJournal of Neuroscience
Volume37
Issue number38
DOIs
Publication statusPublished - Sep 20 2017

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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