Window of opportunity for human amnion epithelial stem cells to attenuate astrogliosis after umbilical cord occlusion in preterm fetal sheep (2022)

There is increasing evidence that administration of many types of stem cell, including human amnion epithelial cells (hAECs), can reduce hypoxic-ischemic injury, including in the perinatal brain. However, the therapeutic window for single dose treatment is not known. We compared the effects of early and delayed intracerebroventricular administration of hAECs in fetal sheep at 0.7 gestation on brain injury induced by 25 minutes of complete umbilical cord occlusion (UCO) or sham occlusion. Fetuses received either 1 × 106 hAECs or vehicle alone, as an infusion over 1 hour, either 2 or 24 hours after UCO. Fetuses were killed for brain histology at 7 days post-UCO. hAEC infusion at both 2 and 24 hours had dramatic anti-inflammatory and anti-gliotic effects, including significantly attenuating the increase in microglia after UCO in the white and gray matter and the number of astrocytes in the white matter. Both protocols partially improved myelination, but had no effect on total or immature/mature numbers of oligodendrocytes. Neuronal survival in the hippocampus was increased by hAEC infusion at either 2 or 24 hours, whereas only hAECs at 24 hours were associated with improved neuronal survival in the striatum and thalamus. Neither protocol improved recovery of electroencephalographic (EEG) power. These data suggest that a single infusion of hAECs is anti-inflammatory, anti-gliotic, and neuroprotective in preterm fetal sheep when given up to 24 hours after hypoxia-ischemia, but was associated with limited white matter protection after 7 days recovery and no improvement in the recovery of EEG power.

Original languageEnglish
Pages (from-to)427-440
Number of pages14
JournalStem Cells Translational Medicine
Volume10
Issue number3
DOIs
Publication statusPublished - Mar 2021
  • asphyxia
  • inflammation
  • neuroprotection
  • preterm birth
  • stem cells
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  • BIBTEX
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Davidson, J. O., van den Heuij, L. G., Fraser, M., Wassink, G., Miller, S. L., Lim, R., Wallace, E. M., Jenkin, G., Gunn, A. J., & Bennet, L. (2021). Window of opportunity for human amnion epithelial stem cells to attenuate astrogliosis after umbilical cord occlusion in preterm fetal sheep. Stem Cells Translational Medicine, 10(3), 427-440. https://doi.org/10.1002/sctm.20-0314

Davidson, Joanne O. ; van den Heuij, Lotte G. ; Fraser, Mhoyra ; Wassink, Guido ; Miller, Suzanne L. ; Lim, Rebecca ; Wallace, Euan M. ; Jenkin, Graham ; Gunn, Alistair J. ; Bennet, Laura. / Window of opportunity for human amnion epithelial stem cells to attenuate astrogliosis after umbilical cord occlusion in preterm fetal sheep. In: Stem Cells Translational Medicine. 2021 ; Vol. 10, No. 3. pp. 427-440.

@article{98496161a3864ddbb790fc89257ea60b,

title = "Window of opportunity for human amnion epithelial stem cells to attenuate astrogliosis after umbilical cord occlusion in preterm fetal sheep",

abstract = "There is increasing evidence that administration of many types of stem cell, including human amnion epithelial cells (hAECs), can reduce hypoxic-ischemic injury, including in the perinatal brain. However, the therapeutic window for single dose treatment is not known. We compared the effects of early and delayed intracerebroventricular administration of hAECs in fetal sheep at 0.7 gestation on brain injury induced by 25 minutes of complete umbilical cord occlusion (UCO) or sham occlusion. Fetuses received either 1 × 106 hAECs or vehicle alone, as an infusion over 1 hour, either 2 or 24 hours after UCO. Fetuses were killed for brain histology at 7 days post-UCO. hAEC infusion at both 2 and 24 hours had dramatic anti-inflammatory and anti-gliotic effects, including significantly attenuating the increase in microglia after UCO in the white and gray matter and the number of astrocytes in the white matter. Both protocols partially improved myelination, but had no effect on total or immature/mature numbers of oligodendrocytes. Neuronal survival in the hippocampus was increased by hAEC infusion at either 2 or 24 hours, whereas only hAECs at 24 hours were associated with improved neuronal survival in the striatum and thalamus. Neither protocol improved recovery of electroencephalographic (EEG) power. These data suggest that a single infusion of hAECs is anti-inflammatory, anti-gliotic, and neuroprotective in preterm fetal sheep when given up to 24 hours after hypoxia-ischemia, but was associated with limited white matter protection after 7 days recovery and no improvement in the recovery of EEG power.",

keywords = "asphyxia, inflammation, neuroprotection, preterm birth, stem cells",

author = "Davidson, {Joanne O.} and {van den Heuij}, {Lotte G.} and Mhoyra Fraser and Guido Wassink and Miller, {Suzanne L.} and Rebecca Lim and Wallace, {Euan M.} and Graham Jenkin and Gunn, {Alistair J.} and Laura Bennet",

year = "2021",

month = mar,

doi = "10.1002/sctm.20-0314",

language = "English",

volume = "10",

pages = "427--440",

journal = "Stem Cells Translational Medicine",

issn = "2157-6564",

publisher = "Alphamed Press",

number = "3",

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Davidson, JO, van den Heuij, LG, Fraser, M, Wassink, G, Miller, SL, Lim, R, Wallace, EM, Jenkin, G, Gunn, AJ & Bennet, L 2021, 'Window of opportunity for human amnion epithelial stem cells to attenuate astrogliosis after umbilical cord occlusion in preterm fetal sheep', Stem Cells Translational Medicine, vol. 10, no. 3, pp. 427-440. https://doi.org/10.1002/sctm.20-0314

Window of opportunity for human amnion epithelial stem cells to attenuate astrogliosis after umbilical cord occlusion in preterm fetal sheep. / Davidson, Joanne O.; van den Heuij, Lotte G.; Fraser, Mhoyra; Wassink, Guido; Miller, Suzanne L.; Lim, Rebecca; Wallace, Euan M.; Jenkin, Graham; Gunn, Alistair J.; Bennet, Laura.

In: Stem Cells Translational Medicine, Vol. 10, No. 3, 03.2021, p. 427-440.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Window of opportunity for human amnion epithelial stem cells to attenuate astrogliosis after umbilical cord occlusion in preterm fetal sheep

AU - Davidson, Joanne O.

AU - van den Heuij, Lotte G.

AU - Fraser, Mhoyra

AU - Wassink, Guido

AU - Miller, Suzanne L.

AU - Lim, Rebecca

AU - Wallace, Euan M.

AU - Jenkin, Graham

AU - Gunn, Alistair J.

AU - Bennet, Laura

PY - 2021/3

Y1 - 2021/3

N2 - There is increasing evidence that administration of many types of stem cell, including human amnion epithelial cells (hAECs), can reduce hypoxic-ischemic injury, including in the perinatal brain. However, the therapeutic window for single dose treatment is not known. We compared the effects of early and delayed intracerebroventricular administration of hAECs in fetal sheep at 0.7 gestation on brain injury induced by 25 minutes of complete umbilical cord occlusion (UCO) or sham occlusion. Fetuses received either 1 × 106 hAECs or vehicle alone, as an infusion over 1 hour, either 2 or 24 hours after UCO. Fetuses were killed for brain histology at 7 days post-UCO. hAEC infusion at both 2 and 24 hours had dramatic anti-inflammatory and anti-gliotic effects, including significantly attenuating the increase in microglia after UCO in the white and gray matter and the number of astrocytes in the white matter. Both protocols partially improved myelination, but had no effect on total or immature/mature numbers of oligodendrocytes. Neuronal survival in the hippocampus was increased by hAEC infusion at either 2 or 24 hours, whereas only hAECs at 24 hours were associated with improved neuronal survival in the striatum and thalamus. Neither protocol improved recovery of electroencephalographic (EEG) power. These data suggest that a single infusion of hAECs is anti-inflammatory, anti-gliotic, and neuroprotective in preterm fetal sheep when given up to 24 hours after hypoxia-ischemia, but was associated with limited white matter protection after 7 days recovery and no improvement in the recovery of EEG power.

AB - There is increasing evidence that administration of many types of stem cell, including human amnion epithelial cells (hAECs), can reduce hypoxic-ischemic injury, including in the perinatal brain. However, the therapeutic window for single dose treatment is not known. We compared the effects of early and delayed intracerebroventricular administration of hAECs in fetal sheep at 0.7 gestation on brain injury induced by 25 minutes of complete umbilical cord occlusion (UCO) or sham occlusion. Fetuses received either 1 × 106 hAECs or vehicle alone, as an infusion over 1 hour, either 2 or 24 hours after UCO. Fetuses were killed for brain histology at 7 days post-UCO. hAEC infusion at both 2 and 24 hours had dramatic anti-inflammatory and anti-gliotic effects, including significantly attenuating the increase in microglia after UCO in the white and gray matter and the number of astrocytes in the white matter. Both protocols partially improved myelination, but had no effect on total or immature/mature numbers of oligodendrocytes. Neuronal survival in the hippocampus was increased by hAEC infusion at either 2 or 24 hours, whereas only hAECs at 24 hours were associated with improved neuronal survival in the striatum and thalamus. Neither protocol improved recovery of electroencephalographic (EEG) power. These data suggest that a single infusion of hAECs is anti-inflammatory, anti-gliotic, and neuroprotective in preterm fetal sheep when given up to 24 hours after hypoxia-ischemia, but was associated with limited white matter protection after 7 days recovery and no improvement in the recovery of EEG power.

KW - asphyxia

KW - inflammation

KW - neuroprotection

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Davidson JO, van den Heuij LG, Fraser M, Wassink G, Miller SL, Lim R et al. Window of opportunity for human amnion epithelial stem cells to attenuate astrogliosis after umbilical cord occlusion in preterm fetal sheep. Stem Cells Translational Medicine. 2021 Mar;10(3):427-440. https://doi.org/10.1002/sctm.20-0314

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