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 language | English |
|---|---|
| Pages (from-to) | 9269-9287 |
| Number of pages | 19 |
| Journal | Journal of Neuroscience |
| Volume | 37 |
| Issue number | 38 |
| DOIs | |
| Publication status | Published - Sep 20 2017 |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
Cite this
Systemic neutrophil depletion modulates the migration and fate of transplanted human neural stem cells to rescue functional repair. / Nguyen, Hal X.; Hooshmand, Mitra J.; Saiwai, Hirokazu; Maddox, Jake; Salehi, Arjang; Lakatos, Anita; Nishi, Rebecca A.; Salazar, Desiree; Uchida, Nobuko; Anderson, Aileen J.
In: Journal of Neuroscience, Vol. 37, No. 38, 20.09.2017, p. 9269-9287.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Systemic neutrophil depletion modulates the migration and fate of transplanted human neural stem cells to rescue functional repair
AU - Nguyen, Hal X.
AU - Hooshmand, Mitra J.
AU - Saiwai, Hirokazu
AU - Maddox, Jake
AU - Salehi, Arjang
AU - Lakatos, Anita
AU - Nishi, Rebecca A.
AU - Salazar, Desiree
AU - Uchida, Nobuko
AU - Anderson, Aileen J.
PY - 2017/9/20
Y1 - 2017/9/20
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85029758052&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.2785-16.2017
DO - 10.1523/JNEUROSCI.2785-16.2017
M3 - Article
C2 - 28847814
AN - SCOPUS:85029758052
VL - 37
SP - 9269
EP - 9287
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 38
ER -