Neuroprotection of the hypoxic-ischemic mouse brain by human CD117CD90CD105amniotic fluid stem cells

Michelangelo Corcelli; Kate Hawkins; Filipa Vlahova; Avina Hunjan; Kate Dowding; Paolo De Coppi; Anna L David; Donald Peebles; Pierre Gressens; Henrik Hagberg; Mariya Hristova; Pascale V Guillot

doi:10.1038/s41598-018-20710-9

Neuroprotection of the hypoxic-ischemic mouse brain by human CD117CD90CD105amniotic fluid stem cells

Michelangelo Corcelli, Kate Hawkins, Filipa Vlahova, Avina Hunjan, Kate Dowding, Paolo De Coppi, Anna L David, Donald Peebles, Pierre Gressens, Henrik Hagberg, Mariya Hristova, Pascale V Guillot

Maternal and Fetal Medicine Department, Institute for Women's Health, University College London, London, United Kingdom.
Stem Cells and Regenerative Medicine Department, Great Ormond Street Institute for Child Health, University College London, London, United Kingdom.
UCL Hospitals NHS Foundation Trust
University of Paris VII - Denis Diderot University
University of Gothenburg
University College London, Institute for Women's Health, Maternal and Fetal Medicine Department, London, UK. [email protected].
University College London, Institute for Women's Health, Maternal and Fetal Medicine Department, London, UK. [email protected].

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Abstract

Human amniotic fluid contains two morphologically-distinct sub-populations of stem cells with regenerative potential, spindle-shaped (SS-hAFSCs) and round-shaped human amniotic fluid stem cells (RS-hAFSCs). However, it is unclear whether morphological differences correlate with functionality, and this lack of knowledge limits their translational applications. Here, we show that SS-hAFSCs and RS-hAFSCs differ in their neuro-protective ability, demonstrating that a single contralateral injection of SS-hAFSCs into hypoxic-ischemic P7 mice conferred a 47% reduction in hippocampal tissue loss and 43-45% reduction in TUNEL-positive cells in the hippocampus and striatum 48 hours after the insult, decreased microglial activation and TGFβ1 levels, and prevented demyelination. On the other hand, RS-hAFSCs failed to show such neuro-protective effects. It is possible that SS-hAFSCs exert their neuroprotection via endoglin-dependent inhibition of TGFβ1 signaling in target cells. These findings identify a sub-population of CD117+CD90+CD105+stem cells as a promising source for the neuro-protection of the developing brain.

Original language	English
Article number	2425
Journal	Scientific Reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-20710-9
Publication status	Published - 5 Feb 2018

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Neuroprotection of the hypoxic-ischemic_CORCELLI_Accepted23January2018_GOLD VoR (CC BY)Final published version, 6.24 MBLicence: CC BY

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title = "Neuroprotection of the hypoxic-ischemic mouse brain by human CD117CD90CD105amniotic fluid stem cells",

abstract = "Human amniotic fluid contains two morphologically-distinct sub-populations of stem cells with regenerative potential, spindle-shaped (SS-hAFSCs) and round-shaped human amniotic fluid stem cells (RS-hAFSCs). However, it is unclear whether morphological differences correlate with functionality, and this lack of knowledge limits their translational applications. Here, we show that SS-hAFSCs and RS-hAFSCs differ in their neuro-protective ability, demonstrating that a single contralateral injection of SS-hAFSCs into hypoxic-ischemic P7 mice conferred a 47% reduction in hippocampal tissue loss and 43-45% reduction in TUNEL-positive cells in the hippocampus and striatum 48 hours after the insult, decreased microglial activation and TGFβ1 levels, and prevented demyelination. On the other hand, RS-hAFSCs failed to show such neuro-protective effects. It is possible that SS-hAFSCs exert their neuroprotection via endoglin-dependent inhibition of TGFβ1 signaling in target cells. These findings identify a sub-population of CD117+CD90+CD105+stem cells as a promising source for the neuro-protection of the developing brain.",

author = "Michelangelo Corcelli and Kate Hawkins and Filipa Vlahova and Avina Hunjan and Kate Dowding and {De Coppi}, Paolo and David, {Anna L} and Donald Peebles and Pierre Gressens and Henrik Hagberg and Mariya Hristova and Guillot, {Pascale V}",

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AU - Corcelli, Michelangelo

AU - Hawkins, Kate

AU - Vlahova, Filipa

AU - Hunjan, Avina

AU - Dowding, Kate

AU - De Coppi, Paolo

AU - David, Anna L

AU - Peebles, Donald

AU - Gressens, Pierre

AU - Hagberg, Henrik

AU - Hristova, Mariya

AU - Guillot, Pascale V

PY - 2018/2/5

Y1 - 2018/2/5

N2 - Human amniotic fluid contains two morphologically-distinct sub-populations of stem cells with regenerative potential, spindle-shaped (SS-hAFSCs) and round-shaped human amniotic fluid stem cells (RS-hAFSCs). However, it is unclear whether morphological differences correlate with functionality, and this lack of knowledge limits their translational applications. Here, we show that SS-hAFSCs and RS-hAFSCs differ in their neuro-protective ability, demonstrating that a single contralateral injection of SS-hAFSCs into hypoxic-ischemic P7 mice conferred a 47% reduction in hippocampal tissue loss and 43-45% reduction in TUNEL-positive cells in the hippocampus and striatum 48 hours after the insult, decreased microglial activation and TGFβ1 levels, and prevented demyelination. On the other hand, RS-hAFSCs failed to show such neuro-protective effects. It is possible that SS-hAFSCs exert their neuroprotection via endoglin-dependent inhibition of TGFβ1 signaling in target cells. These findings identify a sub-population of CD117+CD90+CD105+stem cells as a promising source for the neuro-protection of the developing brain.

AB - Human amniotic fluid contains two morphologically-distinct sub-populations of stem cells with regenerative potential, spindle-shaped (SS-hAFSCs) and round-shaped human amniotic fluid stem cells (RS-hAFSCs). However, it is unclear whether morphological differences correlate with functionality, and this lack of knowledge limits their translational applications. Here, we show that SS-hAFSCs and RS-hAFSCs differ in their neuro-protective ability, demonstrating that a single contralateral injection of SS-hAFSCs into hypoxic-ischemic P7 mice conferred a 47% reduction in hippocampal tissue loss and 43-45% reduction in TUNEL-positive cells in the hippocampus and striatum 48 hours after the insult, decreased microglial activation and TGFβ1 levels, and prevented demyelination. On the other hand, RS-hAFSCs failed to show such neuro-protective effects. It is possible that SS-hAFSCs exert their neuroprotection via endoglin-dependent inhibition of TGFβ1 signaling in target cells. These findings identify a sub-population of CD117+CD90+CD105+stem cells as a promising source for the neuro-protection of the developing brain.

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Neuroprotection of the hypoxic-ischemic mouse brain by human CD117CD90CD105amniotic fluid stem cells

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