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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amniotic Fluid / cytology*
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Amniotic Fluid / metabolism
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Animals
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Antigens, CD / genetics
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Antigens, CD / metabolism
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Apoptosis
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Brain Ischemia / genetics
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Brain Ischemia / metabolism
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Brain Ischemia / pathology
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Brain Ischemia / therapy*
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Cell Lineage
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Cell- and Tissue-Based Therapy / methods
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Corpus Striatum / metabolism
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Corpus Striatum / pathology
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Demyelinating Diseases / genetics
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Demyelinating Diseases / metabolism
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Demyelinating Diseases / pathology
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Demyelinating Diseases / prevention & control*
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Disease Models, Animal
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Endoglin / genetics
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Endoglin / metabolism
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Gene Expression
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Hippocampus / metabolism
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Hippocampus / pathology
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Humans
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Hypoxia / genetics
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Hypoxia / metabolism
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Hypoxia / pathology
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Hypoxia / prevention & control*
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In Situ Nick-End Labeling
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Mice
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Mice, Inbred C57BL
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Microglia / metabolism
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Microglia / pathology
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Neuroprotection / physiology*
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Stem Cell Transplantation*
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Stem Cells / cytology*
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Stem Cells / metabolism
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Transforming Growth Factor beta1 / genetics
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Transforming Growth Factor beta1 / metabolism
Substances
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Antigens, CD
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Endoglin
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Eng protein, mouse
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Tgfb1 protein, mouse
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Transforming Growth Factor beta1